Iris Isabel Lopez (Original Language)

Name of Lead Author: Iris Isabel López
Organization: CONASIDA/AMUGEN
Country: Guatemala

Abstract

Se ha denunciado en medios de comunicación , cuando ha existido desabastecimiento parcial, Guatemala es el país de la región que compra más cara la TARV debido a la propiedad intelectual de los medicamentos antirretrovirales. Desde el año 2007 he apoyado a Guatemala buscando terapia antirretroviral para personas con VIH, con el apoyo de Aid for Aids, hemos logrado apalear la necesidad en los tres esquemas de tratamiento. La protección a la propiedad intelectual de las moléculas de medicamentos como ejemplo lopinavir/ritonavir, han sido una lucha constante, debido que ha sido utilizado para un número de 2000 pacientes, que incluye a 81 embarazadas, 205 niñez en la presentación de kaletra . Lo que hace necesaria invocar los derechos humanos de la vida y la salud, y por el apoyo del Fondo Mundial se lograron comprar y abastecer el medicamento hasta el 2015. Según estudios comparativos se adquiría en compra local el costo era $ 128.00 , si adquirían con el Fondo Rotatorio su costo era de $ 80.00, a través de Fondo Mundial $ 60.00 y si se utilizaran medicamentos genéricos su costo sería de $ 34.00 aproximadamente. Actualmente la Corte de Constitucionalidad amparó a una empresa distribuidora de medicamentos prohibiendo el ingreso de medicamentos genéricos y estos son beneficiosos ya que llenan los criterios de la Organización Mundial de la Salud bioseguridad, bioequivalencia, calidad y menor costo; este último criterio permite una mayor cobertura con una inversión reducida que garantice calidad de vida. La legislación guatemalteca da preeminencia al Derecho Internacional en materia de Derechos Humanos, por lo que se debe considerar el derecho a la vida y la salud, como fundamentales en la adquisición de medicamentos, sobre todo porque si se vive con VIH existen otras enfermedades degenerativas que requieren tratamiento que no son cubiertos por el Estado de Guatemala.

Submission

La corrupción en Guatemala, ha afectado el sistema de Salud Pública, violentando los Derechos Humanos.

La Constitución Política de Guatemala, en su artículo 93 a 95, reconoce el Derecho a la Salud. “Derecho a la salud. El goce de la salud es derecho fundamental del ser humano, sin discriminación alguna”.

Artículo 94.- Obligación del Estado, sobre salud y asistencia social. El Estado velará por la salud y la asistencia social de todos los habitantes. Desarrollará, a través de sus instituciones, acciones de prevención, promoción, recuperación, rehabilitación, coordinación y las complementarias pertinentes a fin de procurarles el más completo bienestar físico, mental y social.

Artículo 95.- La salud, bien público. La salud de los habitantes de la Nación es un bien público. Todas las personas e instituciones están obligadas a velar por su conservación y restablecimiento.

Y en el artículo 98 Artículo 98.- Participación de las comunidades en programas de salud. Las comunidades tienen el derecho y el deber de participar activamente en el planificación, ejecución y evaluación de los programas de salud Esto garantiza y obliga que la sociedad civil organizada participe activamente en la búsqueda del bien común.

En el tema del acceso a los medicamentos retrovirales, tenemos cuatro escenarios distintos
1. Adquisición de medicamentos antirretrovirales y la legislación que ha sido modificada para poder realizar compras internaciones, ya que la legislación contravenía y obstaculizaba la compra por el Fondo Estratégico de OPS/OMS.
2. Registro de medicamentos con propiedad intelectual desde la molécula para su elaboración que han perjudicado a las personas con VIH, un ejemplo Lopinavir/Ritonavir y Kaletra en el caso de la niñez con VIH.
3. Esquemas de Tercera Línea de tratamiento antirretroviral que por espacio de tres años han sido beneficiados por donaciones internacionales de Aid For Aids y Aids Healthcare Fundation
4. Amparo que protege y beneficia a particulares negociantes de la salud que venden productos farmacéuticos a precios onerosos, tratando de impedir el uso de medicamentos genéricos de menor costo. Adquisición de medicamentos antirretrovirales y la legislación que ha sido modificada para poder realizar compras internaciones, ya que la legislación contravenía y obstaculizaba la compra por el Fondo Estratégico de OPS/OMS.
1. los medicamentos genéricos, especialmente antirretrovirales, se adquieren por el Fondo Rotatorio de la OPS, según la legislación guatemalteca la compra de medicamentos debe realizarse con los requerimientos de la ley de Contrataciones del Estado (Decreto 57-92) y deben ser subidos al sistema de Adquisiciones y Contrataciones del Estado -GUATECOMPRAS-.

En años anteriores este proceso limitaba que se adquirieran los medicamentos antirretrovirales y otros medicamentos distribuidos por el Ministerio de Salud Pública y Asistencia Social a la población de escasos recursos para la atención a la morbilidad que padecen.

En el año 2012 al 2014 fue necesario que se incluyera la modificación al artículo 5 que reformaba los artículos 22 y 25 de Decreto 57-92, pero para evitar estar recordando cada año su inclusión; el Acta 09-2015 emitida por el Congreso de la República de Guatemala que contiene las Reformas a dicha ley del Contrataciones del Estado Decreto 57-92 (artículo 25 adiciona el artículo 54 bis Subasta a la inversa): “b) El Ministerio de Salud Pública y Asistencia Social y el Instituto Guatemalteco de Seguridad Social, podrán adquirir de manera directa vacunas, medicamentos antirretrovirales, métodos de planificación familiar, fármacos, micronutrientes, suministros quirúrgicos y de laboratorio, al amparo de convenios o tratados internacionales suscritos con los organismos siguientes: La Oficina Panamericana de la Salud/Organización Mundial de Salud OPS/OMS; agencias del Sistema de las Naciones Unidas, el Fono Mundial; l Fondo de Poblaciones de las Naciones Unidas –UNFPA- o por Negociación Regional de Precios que efectúe la Secretaria Ejecutiva del Consejo de Ministros de Salud de Centroamérica y República Dominicana –COMISCA-. La ejecución de estas negociaciones se sujetará a los términos de los instrumentos contractuales suscritos;”.

Queda pendiente la elaboración del reglamento y su aplicación que quedara a cargo del Ministerio de Salud Pública y Asistencia Social, buscando la opción de compras internaciones de menor costo y lograr mayor cobertura, por lo tanto más personas puedan adquirir medicamentos de calidad.

Registro de medicamentos con propiedad intelectual desde la molécula para su elaboración que han perjudicado a las personas con VIH, un ejemplo Lopinavir/Ritonavir y Kaletra en el caso de la niñez con VIH.

Existe el atencecente de una farmacéutica que logró por diez años la propiedad intelectual de la molécula de la fabricación de Lopinavir/Ritonavir incluyendo el medicamento pediátrico denominado Kaletra, esto afectó directamente a las personas con VIH bajo este tratamiento, por lo oneroso y que en determinado momento a pesar de argumentarles que se protegían los Derechos Humanos de la Vida y la Salud amenazaron que no permitirían el ingreso de los medicamentos y que demandarían internacionalmente al Estado de Guatemala. UNOPS trató de mediar con la farmacéutica y sin importar lo perjudicial que era para las personas con VIH, no recibir los medicamentos a tiempo, fueron insensibles ya que protegían sus intereses particulares.

Esta situación se trató de subsanar con la Unidad Jurídica del Ministerio de Salud Pública y Asistencia Social, la Subvención de VIH del Proyecto del Fondo Mundial para el sida, la Tuberculosis y la Malaria y la Comisión Nacional Multisectorial de Organizaciones que Velan y Trabajan en la Prevención de ITS/VIH/sida –CONASIDA-, fundamentando e invocando los Derechos Humanos, que tienen preeminencia sobre el Derecho Interno en materia de Derechos Humanos en Guatemala.

El medicamento Lopinavir/Ritonavir, se emplean en el tratamiento del VIH, cuyo mecanismo de acción consiste en la inhibición de la proteasa, una proteína que juega un papel importante en el ciclo de vida del virus, particularmente en su fase de replicación. El Lopinavir en sí se descompone rápidamente en el organismo, y lo que se busca al combinarlo con Ritonavir es desacelerar este proceso y aumentar el tiempo de permanencia del lopinavir en el torrente sanguíneo.

El 15 de septiembre del 2000, la Administración de Alimentos y Medicamentos de los Estados unidos (FDA) aprobó el Lopinavir/Ritonavir en cápsula y líquido para uso con otros antirretrovirales para el tratamiento de la infección por el VIH en adultos y niños mayores de 6 meses. El Lopinavir/Ritonavir en tableta fue aprobado por la FDA el 28 de octubre del 2005.

La indicación en Guatemala es tratamiento de la infección por VIH; en el país existen dos formas farmacéuticas registradas por abbott: 1) Tabletas (Lopinavir 200mg +Ritonavir 50mg) y 2) solución oral (Lopinavir 80mg + Ritonavir 20mg). En las guías de tratamiento, publicadas por el Ministerio de Salud Pública y Asistencia Social en el año 2010, se considera como un tratamiento de primera línea para mujeres embarazadas y de segunda línea ante fracaso terapéutico de un primer esquema, también es considerado de primera línea solo cuando no puede emplearse por alguna razón Efavirenz ni Nevirapina, en combinación con Zidovudina y Lamivudina, antiretrovirales de elección para iniciar el tratamiento con ARV.

Cabe señalar que el costo de compra de medicamentos de marca en Guatemala es considerados altos a pesar que la mayoría se adquiere a través del Fondo Estratégico de la Organización Panamericana de la Salud -OPS/OMS-, las principales razones para que esto suceda es la extensión y protección de patente de invención y dato de prueba en favor de las casas farmacéuticas. Ejemplo de esto son los medicamentos Lopinavir/ritonavir (ALUVIA) y Emtricitabina+tenofovir (TRUVADA)

En tal sentido, el Ministerio de Salud Pública y Asistencia Social se planteado la necesidad de proveer medicamentos de alta calidad y bajo precio para lo cual se ha publicado el Acuerdo Ministerial 472-2012 (13 de agosto de 2012) declarando de alto interés terapéutico y sin ningún interés de comercializarlo el medicamento Lopinavir/Ritonavir.

El Ministerio de Salud Pública y Asistencia Social de la República de Guatemala, es Receptor Principal de la Subvención denominada Intensificación de las Acciones de Prevención y Atención de VIH-SIDA En Grupos Vulnerables y Áreas Prioritarias de Guatemala, financiada por el Fondo Mundial; a través de dicha donación y con la aprobación expresa del Fondo Global adquirirá el medicamento Lopinavir/Ritonavir en versión genérica.

Para lo cual la UNOPS actuará como Agente de Compras para apoyar al gobierno de Guatemala en el proceso de adquisición de dicho medicamento a fin de garantizar el tratamiento de 1652 pacientes entre ellos mujeres embarazadas, y pacientes de rescate y el suministro, abastecimiento y distribución oportuna para otros beneficiarios del Programa Nacional de ITS, VIH, SIDA que utilicen el medicamento de manera de contribuir a mantener una adecuada cobertura de atención.

Se ha requerido oficialmente a UNOPS proceda a la adquisición de un lote inicial 11,071 frascos de Lopinavir/Ritonavir de composición genérica. El contenido especificado de cada frasco es de 120 tabletas y cada tableta con una concentración certificada de 200/50 mg del principio activo Lopinavir/Ritonavir. El Ministerio de Salud Pública y Asistencia Social ha proporcionado en un documento por separado las especificaciones técnicas del medicamentos a UNOPS y ha solicitado que los documentos de embarque y de facturación a ser acompañados con el Original del Certificado de calidad del o de los Lotes de producción; la fotocopia simple del Certificado de Buenas prácticas de Manufactura extendido por la autoridad reguladora del país de origen; y la fotocopia simple del Certificado de libre comercialización de productos farmacéuticos. (Tipo OPS/OMS) como documentos adicionales a los requeridos para la importación bajo la modalidad de elevado interés terapéutico.

La importación de Lopinavir/Ritonavir genérico permitirá la compra de mayor cantidad de producto en comparación con la compra de medicamento de marca, que en relación a precio equivale al doble del costo. Esto permite realizar una mejor distribución de los recursos para la compra de otros antirretrovirales y de esta forma garantizar el abastecimiento oportuno de los insumos y mejorar la accesibilidad a los tratamientos en Guatemala.

Se espera recibir este producto en versión genérica para mayo del año 2013, en espera de lograr el desaduanaje del medicamento sin inconveniente alguno y en espera de la posible respuesta que la empresa farmacéutica Abbott pueda implementar durante este tiempo para que no se lleve a cabo la internación al país de este producto.

Se adjunta el cuadro con los precios del producto en versión genérica y de marca. La compra para un año de este producto oscila entre los 21,000-26,000 frascos al año.

Tipo de Producto     Precio Frasco
Genérico $30.50
Abbott $62.04

El 2015 venció la propiedad intelectual y es necesario que se garantice la adquisición de la terapia antirretroviral con precios estandarizados, ya que Guatemala, es el país de la región que compra más caro los tratamientos, Lidice López Tocón, realizó un estudio denominado “Dime dónde vives y te diré el precio de tu tratamiento”, este análisis permitió hacer un comparativo de los costos de varios medicamentos.

Esquemas de Tercera Línea de tratamiento antirretroviral que por espacio de tres años han sido beneficiados por donaciones internacionales de Aid For Aids y Aids Healthcare Fundation

Los problemas de desabastecimientos parciales en Guatemala que han sido apoyados por Aid For Aids, han sido esquemas de primera, segunda y tercera línea en particular. Ya que la fármaco resistencia de los medicamentos ya sea por interrupción o el uso prolongado de los mismos, requiere obligatoriamente realizar una vigilancia de tercera generación, denominada genotipo.

En año 2012, se solicitó apoyo para una menor, quien pasó a ser beneficiada directa de Aid For Aids, quienes envían los medicamentos de tercera línea, los que han sido beneficiosos y tiene una muy buena calidad de vida. Terminando los tramites de la menor, se contaba ya con un listado de 19 pacientes más en su mayoría menores, la compra de tratamientos por OPS requiere un promedio de seis meses para recibir los medicamentos en el país, por lo que fue necesario solicitar ayuda y brindarles urgentemente los tratamientos.

En el año 2013 y 2014 por el número de pacientes que se incrementaron, no se pudieron incluir las proyecciones oportunas y se requirió la busca de donaciones de medicamentos y también Aids Healthcare Fundation, brindaron tratamientos de tercera línea.

El Instituto Guatemalteco de Seguridad Social –IGSS- ha violentado los Derechos Humanos y el Decreto 27-2000 Ley General Para El Combate Del Virus De Inmunodeficiencia Humana -VIH- Y Del Síndrome De Inmunodeficiencia Adquirida -Sida- y de la Promoción, Protección Y Defensa de los Derechos Humanos ante el VIH/SIDA Art. 49 Derecho a la seguridad social. Las personas trabajadoras que vivan con el VIH/Sida, que estén bajo la cobertura del Instituto Guatemalteco de Seguridad Social -IGSS-, recibirán los beneficios de éste, sin limitárseles bajo ningún concepto este derecho. Por el carácter crónico de la infección por VIH/Sida, dichos beneficios serán de por vida. Sin embargo, han trasladado a pacientes con VIH con esquema de MARAVIROC, denominado de última generación.

El MARAVIROC, es un medicamento que no se figura en listado de medicamentos antirretrovirales que se adquieren en el Fondo Estratégico de la OPS/OMS, lo que obliga al Ministerio de Salud Pública adquirirlo con compras locales con valores arriba de $ 1.280.00 dólares americanos mensuales por paciente, lo lamentable del traslado de los pacientes con VIH es que no llevan un historial clínico y los criterios para suministrarle dicho tratamiento, por lo que se considera necesario que por lo menos un genotipo, recuento de linfocitos de T CD4 y Carga Viral, lo que podría orientar sí podría funcionar otro medicamento de otro esquema sin dañar la adherencia y el tratamiento del paciente.

La atención integral no se puede negar a ninguna persona que lo requiera, pero si es necesario que se estandarice la Guía de Tratamiento Antirretroviral y de Infecciones Oportunistas en Guatemala, que brinda las combinaciones de tratamiento antirretrovirales por esquema.

Las personas con VIH fueron amparadas para garantizar el tratamiento Antirretroviral tanto el Instituto Guatemalteco de Seguridad Social como a la cohorte nacional atendida por el Ministerio de Salud Pública y Asistencia Social, por la situación de corrupción en los diferentes niveles incluyendo en Salud Pública.

Amparo que protege y beneficia a particulares negociantes de la salud que venden productos farmacéuticos a precios onerosos, tratando de impedir el uso de medicamentos genéricos de menor costo.

Otra situación que preocupa fue el Amparo interpuesto Por J. I. Cohen y que fue declarado con lugar por los Honorables Magistrados de la Corte de Constitucionalidad, de fecha 17 de noviembre de 2015.

El amparo interpuesto por J, I Cohen, S. A. (1569-2015 del 17/11/ 2015), beneficia el interés de los distribuidores de productos farmacéuticos ignorando el bienestar de la población, ha habido rechazos generalizados de la sociedad civil guatemalteca incluyendo a las autoridades de salud pública, no lo han declarado sin lugar.

Recientemente en la primera semana del mes de enero 2016, en medios escritos ha estado circulando un CAMPO PAGADO que manifiesta: “J. I. Cohen, S. A. ACLARA La sentencia de la Corte de Constitucionalidad de fecha 17 de Noviembre de 2015 identificada en el expediente 1569-2015 aplica aproximadamente el 6% de los productos registrados en Guatemala, por no encontrarse estos dentro de la Farmacopeas (Artículo 19, Acuerdo Gubernativo 712-99).

Las Farmacopeas contienen miles de substancias activas, que son la base para la fabricación de genéricos registrados en Guatemala NO les aplica la sentencia del 17 de noviembre y por lo tanto NO se les requiere la presentación de estudios toxicológicos ni clínicos ya que al basar su fabricación en los estándares que aparecen en dichas farmacopeas, los estudios toxicológicos y clínicos realizados por el innovador respaldan su seguridad y eficacia. Para el 6% estimado de los productos a los que si aplica la Sentencia de la Corte de Constitucionalidad, existen otras opciones y alternativas terapéuticas como medicamentos genéricos que forman parte de 94% restante que ya se encuentra en las farmacopeas. Por lo tanto, toda la población tiene y seguirá teniendo acceso a medicamentos genéricos seguros y eficaces y de calidad comprobada. Proteger el negocio de una minoría de productos que no han demostrado su seguridad y eficacia, no solo pone en riesgo el derecho a la salud y a la vida de los habitantes, sino pone en riesgo la base del orden de toda la sociedad al quebrantar el estado de derecho. Guatemala, enero 2016”.

En el caso de las personas con Infecciones Oportunistas causadas por Histoplasmosis, que fueron atendidas en el Hospital San Juan de Dios, fallecieron varias personas con VIH dado que requieren el medicamento denominado Anfotericina B, es un medicamento de uso hospitalario, un aproximado de 13 pacientes requerían utilizarlo, el tratamiento por paciente era de 14 frascos con un valor de $ 7.88 dólares americanos por frasco; sin embargo, cuando el Hospital quiso realizar la compra el valor que los distribuidores locales ofertaron era de $ 131.40 dólares y también adujeron que estaba escaso. En este caso se puede evidenciar que por lo oneroso y escaso del medicamento, el Hospital no pudo brindar la atención adecuada a los pacientes, esta situación cobro vidas y el caso es llevado por la Procuraduría de Derechos Humanos.

Es indignante ver como los señores Magistrados protegen intereses de personas particulares negociantes de la salud y se evidencia el atropello a los Derechos Humanos especialmente el derecho a la salud y el Derecho a la vida. Por lo anterior, se infiere que se ha estado violando tanto los derechos de las personas que viven con VIH, como se ha estado contraviniendo la misma constitución política de la República de Guatemala.

Bibliography and References

Constitución Política de la República de Guatemala. 
http://www.ine.gob.gt/archivos/informacionpublica/ConstitucionPoliticadelaRepublicadeGuatemala.pdf
Declaración Universal de Derechos Humanos
http://unesdoc.unesco.org/images/0017/001790/179018m.pdf
Ley de Contrataciones del Estado Decreto 57-92
http://www.sice.oas.org/investment/NatLeg/GTM/ContratsEstado_s.pdf
Decreto 09-2015 del Congreso de la República de Guatemala
http://www.congreso.gob.gt/manager/images/E2926A12-DAF2-44DC-10F1-DFBC6F22A787.pdf
Sistema de Adquisiciones y Contrataciones del Estado
http://www.guatecompras.gt/
Acuerdo Ministerial 472-2012
http://www.infile.com/leyes/visualizador_demo/index.php?id=66531
Estudio Dime dónde vives y te diré cuanto cuesta tu tratamiento por Lidice López T.
http://www.portalsida.org/repos/Un%20breve%20estudio%20sobre%20precios%20de%20ARV%20en%20Centroam%C3%A9rica.pdf
Amparo 1569-2015 a Favor de J. I. Cohen
http://www.velocidadmaxima.com/forum/showthread.php?t=520047

Margaret Ewen and David Beran, Health Action International

Lead Authors: Margaret Ewen and David Beran
Organization: Health Action International; Geneva University Hospitals and University of Geneva
Country: Netherlands and Switzerland

Abstract

Ensuring access to medicines is an essential priority of the WHO Global Action Plan on non-communicable diseases, key to achieving the health target of the Sustainable Development Goals, and contributes to the strengthening of health systems and Universal Health Coverage. However, access to essential medicines for diabetes, especially insulin, has had insufficient attention despite evidence of its low availability and poor affordability in many countries across the globe. The reasons for poor affordability of insulin appear to be multifaceted. Firstly, three companies dominate the market which limits competition. Unlike other medicines, the production of biosimilar (generic) insulin by others has had minimal impact on the global insulin market. Nationally, mark-ups (often uncontrolled in low- and middle-income countries), taxes, duties and other costs in the pharmaceutical supply chain add to the manufacturers’ price and push prices up to often unaffordable levels. Factors contributing to poor insulin availability include inadequate quantification at the national level, inequitable in-country distribution, and poor determination of needs at lower levels of the health system. These barriers contribute to the stark reality that of the 100 million people who need insulin, only one in two can rely on regular and affordable access.

In this contribution, we outline why current initiatives are insufficient to significantly improve access to insulin, and the work underway by the Addressing the Challenge and Constraints of Insulin Sources and Supply (ACCISS) Study group to develop interventions that provide sustainable solutions. These include allocating a small proportion of the existing diabetes funding for innovation in the delivery of insulin, creating a regulatory framework for biosimilars, and instigating a global compact with industry to ensure more affordable human insulins in vials are not be taken off the market. 

Submission

Access to insulin: current status and global policy implications

Insulin was first discovered in 1921 and has been on the WHO Essential Medicines List since 1977, yet on World Diabetes Day in 2013, UN Secretary General Ban Ki Moon had to re-highlight that “nearly 100 years after insulin was first used to save the life of a diabetic patient, people around the world still die because they cannot access this hormone”. Insulin is essential for survival for type 1 diabetes patients and without it individuals face death within a matter of weeks. It is also used for the management of 10-30% of cases of type 2 diabetes.1 Worldwide, 100 million people need access to the insulin, yet currently one in two of these people cannot rely on an adequate supply due to a multitude of barriers to affordability and availability. These barriers have a devastating impact; currently, the most common cause of death for a child with type 1 diabetes is due to lack of insulin. Poor access to insulin can translate into a life expectancy for a child with type 1 diabetes in sub-Saharan Africa as low as one year, in comparison to close to a full life expectancy for a child born in a high-income country. Issues around insulin affordability and availability do not just affect low- and middle-income countries. In a study of diabetes in a US inner city setting, the leading cause of diabetic ketoacidosis was insulin discontinuation, with 27% of patients reporting no money to buy insulin.2 The issue of access and affordability has also become a problem for European countries dealing with and rising health budgets.

Over the past few decades, several declarations on tackling diabetes have been made by international organisations and societies e.g. from the St Vincent Declaration (1989) between the European branches of WHO and International Diabetes Federation (IDF), the Kos Declaration of the International Society for Pediatric and Adolescent Diabetes (1993) to ensure access to insulin, and the IDF Melbourne Declaration (2013) also on access to medicines. However, these statements have not yielded a definitive response to adequately address the complexities of access to insulin. Until the UN General Assembly on NCDs in 2011, little attention was given to access to medicines for NCDs. Moreover, despite being the main cause of mortality worldwide, with 63% of total deaths, NCDs remained off the global development agenda until the recent 2015 Sustainable Development Goals.

The WHO’s Global Action Plan on Non-Communicable Diseases 2013-2020 provides a clear target on access to medicines for chronic conditions: “80% of availability of the affordable basic technologies and essential medicines, including generics, required to treat major NCDs in both public and private facilities” In addition, WHO guidelines on insulin are under development, making this an opportune time to focus on eliminating barriers to accessing insulin. The benefits of improving access to insulin are clear i.e. longer life expectancies for people living with type 1 diabetes, and a decrease in blindness, amputations and kidney failures and premature mortality for people with type 1 or type 2 diabetes. Furthermore, barriers to access to medicines impede the achievement of Universal Health Coverage. The Director General of the WHO stated in 2013 that achieving Universal Health Coverage was essential to avoid individuals having to face “catastrophic health expenditures that drive households into poverty”.3 From a human rights perspective, access to insulin is a fundamental component of a strong health system that upholds the right to health, equality and non-discrimination, development and living a life in dignity.

This contribution to the UN Secretary General Panel on Access to Medicines will address current issues and barriers to access, the work underway in the ACCISS Study, and some initial solutions for tackling the problem. 

Barriers impacting availability and affordability of insulin

Studies have identified a variety of barriers to accessing insulin, at both international and national levels. But two key barriers stand out i.e. low availability in outlets and high prices.

Insulin is different to most other medicines in that the market is dominated by three companies, currently accounting for about 90% of the global insulin market in terms of value and volume.1 This restricts price competition and enables the three companies to shape the market, including the promotion of higher priced analogue insulins rather than lower priced human insulins. An insulin price survey, to be released on World Health Day 2016 by the ACCISS Study, shows patients were paying about $7 versus $42 for 10ml of human and analogue insulin respectively in the public sector, and $17 versus $40 in the private sector.4 In parallel to an increase in insulin usage, analogue insulin is taking increasingly larger shares of the market.

Intellectual property is not a barrier to accessing the insulin molecule, but shifts to use of insulin delivered in pen devices, which are patented, is likely to be a barrier in many settings.

Unlike antiretrovirals (ARVs) and other medicines, the production of biosimilar insulin is complex both in terms of the process of creating an exact biological copy and in ensuring quality. Because of this, regulatory requirements are more complex for biosimilar insulin compared to generic small molecules, which adds a further barrier to competition. 

Many barriers to access are also due to how insulin is purchased and used at the national level. Firstly, insulin is often subject to import duties (ranging from 0-15%) and taxes (0% to 25%).5 Then mark-ups (often uncontrolled in low and middle-income countries) and other charges are applied in the supply system, which drive up patient prices even further.

Purchasing insulin places a large financial burden on people with diabetes and their families, especially in low- and middle-income countries. Affordability to the individual is an issue, even when buying in the public sector. For example, the lowest paid unskilled government worker in Burundi has to work six days to pay for 10ml human insulin in the public sector. In the public sector in Indonesia, 3 days’ wages are needed to by human insulin and 6 days’ wages to buy analogue insulin.4

The limited number of suppliers can impact government procurement, and hence insulin availability, in some countries. For example, in Mali a minimum of three bids are required as part of the tender process which is challenging when there are so few suppliers. In some countries, governments prioritise other medicines when purchasing or difficulties are encountered when distributing medicines particularly to rural areas. Transportation and storage costs of insulin movement from urban to rural areas can result in higher patient prices.

In early 2015, Health Action International in collaboration with Boston University School of Public Health, the Geneva University Hospitals, and University of Geneva Division of Tropical and Humanitarian Medicine launched its three year ACCISS Study. The aim is to provide a comprehensive, pioneering, evidence-base on the global insulin market, in particular on the type, extent, and effect of barriers to global insulin access. Based on the first year of the study, the main innovation will not come from new formulations of insulin, but rather innovative models of supply and interventions. These interventions will be developed as the study progresses. That said, some actions are already apparent as outlined in the call to action.

Call to action

Many diabetes organisations and pharmaceutical companies have worked towards providing insulin for those in need, through donations programmes such as IDF’s Life for a Child and differential pricing schemes. However, these approaches are small-scale, do not provide long-term solutions, and rarely tackle the barriers to access in the first place. For example, the selection of countries for differential pricing schemes is usually based on a country’s income, therefore often excludes middle-income countries, where large segments of the population can be poor.

Although the approach to tackling access to insulin is different to that of ensuring access to ARVs, certain lessons can be learnt. Firstly, while international financing schemes tend to fund ARVs, insulin is purchased from national budgets with no external funding. In 2000, Yudkin estimated that for highly indebted poor countries, $3-5 million would be sufficient to provide insulin for all needing this medicine. This is a small amount compared to the funding allocated to researching a cure for type 1 diabetes by foundations, governments and the private sector. The US National Institute for Health designated more than one billion dollars for diabetes research in 2015 alone. We call for a small portion of this funding, such as 5%, to be allocated to improving access to insulin for patients, and for improving health systems.

Secondly, in the fight for affordability of ARVs, the market was reshaped by the promotion of generic competition, including prequalification, transparency in reporting government procurement prices, and product quality testing. In order to ensure that the quality of generics met national and international standards, WHO developed a prequalification scheme for medicines for HIV/AIDS, malaria and tuberculosis, and has since expanded the programme to other diseases. Insulin is not included in this prequalification scheme. Biosimilar insulins have not impacted the insulin market in the same way that generic ARVs have, a key factor of which is the complexity of proving similarity with the originator. Dealing with this issue is important in improving access to insulin. We call on WHO to investigate the inclusion of insulin in its prequalification scheme, to develop a regulatory framework for biosimilar insulin, and to support governments to procure quality-assured, safe, efficacious and cost-effective insulin products.

To tackle the issue of rising prices due to incremental technology innovations, we also suggest the development of a global compact with the insulin industry; to guarantee that human insulin and insulin in vial form will not be removed from the market.

Innovation in the supply of insulin, active civil society involvement, and funding will be necessary to achieve the Global Action Plan’s target of 80% availability of affordable medicines to treat NCDs, or the more pioneering target of the 100 Campaign of “100% of people living with type 1 diabetes having access to insulin by 2022.”

Challenges lie ahead in developing and implementing these solutions, especially where stakeholders see the existing solutions, such as differential pricing and donations, as sufficient. However, with the newly announced Sustainable Development Goals and work on Universal Health Coverage, now is the time for action to address inequalities in access to insulin. 

Bibliography and References

1.      Wirtz V. Insulin market profile. To be published 7 April 2016 by HAI as part of the ACCISS Study.

2.      Randall L, Begovic J, Hudson M, Smiley D, Peng L, Pitre N, et al. Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Diabetes Care.2011 Sep;34(9):1891-6. PubMedPMID: 21775761. PMCID: 3161256.Epub 2011/07/22. eng.

3.      Opening remarks at a WHO/World Bank ministerial-level meeting on universal health coverage Geneva, Switzerland 18 February 2013 http://www.who.int/dg/speeches/2013/universal_health_coverage/en/

4.      Ewen M, Joosse H-J, Ashigbie P, Beran D, Laing R. Insulin prices. To be published 7 April 2016 by HAI as part of the ACCISS Study.

5.      Kaplan W. Import tariffs and taxes on insulin. To be published 7 April 2016 by HAI as part of the ACCISS Study.

Andrew Hill, Anton Pozniak and James Freeman, Chelsea and Westminster Hospital

Lead Authors: Andrew Hill, Anton Pozniak, and James Freeman
Organization: Chelsea and Westminster Hospital
Country: United Kingdom

Recent analyses have shown that several other major diseases could be treated for very low costs –

1. A 12 week course of treatment for Hepatitis C with generic sofosbuvir (Sovaldi, Gilead) is now on sale in India for under $500, versus the US retail price of $84,000. We have estimated that the cost of mass produced sofosbuvir should fall to under $100 per treatment course in 2016. There are over 150 million people infected with Hepatitis C worldwide, with 700,000 deaths per year. Sofosbuvir in combination with daclatasvir has cured over 90% of people with Hepatitis C in clinical trials. The combined cost of these two drugs could fall below $150 per 12 week treatment course this year. The basic patents on these drugs expire in 2029, but voluntary license agreements allow mass generic production at low costs.

2. A year of treatment with imatinib (Gleevec, Novartis) to treat Chronic Myeloid Leukaemia (CML) is being sold in India for $800, versus the US price of $108,000. We have estimated that imatinib could be mass produced for between $128-$216 per person per year. There are 48,000 new cases of CML each year worldwide. The patent on imatinib has just expired in the USA.

3. A year of treatment with entecavir (Baraclude, Bristol-Myers Squibb) to treat Hepatitis B is being sold in India as a generic for $427, versus the US originator price of $15,000. We have estimated that entecavir could be mass produced for $36 per person per year. Only 0.2 grams of drug are required for a year of treatment, as the dose is only 0.5 milligrams per day. There are over 350 million people infected with Hepatitis B worldwide, with 686,000 deaths from this disease in 2013 alone. The patent on entecavir has already expired in many countries.

4. Generic erlotinib to treat non-small cell lung cancer is being sold in India for $1900 per year, versus the US price of $79,000 from Roche. We have estimated that generic erlotinib could be mass produced for $240 per person per year. There are 440,000 new cases of this type of lung cancer each year, which would be eligible for treatment with generic erlotinib. The patent on erlotinib expires in 2020.

Estimating minimum costs of drug production

Pharmaceutical companies do not normally publish information on the true cost of production of their treatments. Previous estimates of production costs from pharmaceutical companies have been shown to be far higher than the final costs of production from generic companies. For example the HIV drug atazanavir was initially offered for sale in low income countries by Bristol-Myers Squibb for $2000 per person-year; the same drug is now mass produced by generic companies for under $200 per person-year. Likewise, Gilead initially estimated that sofosbuvir would cost at least $1100 per 12 week course to manufacture – the same drug is now being produced in India for under $100.

Estimation of minimum production costs is from two main sources:

1. There is a database showing exports of drugs from India to other countries – this is called www.indiainfodrive.com, and shows the costs per kilogram of “Active Pharmaceutical Ingredient”, or API. This is the actual drug in its pure form, before being formulated into tablets or capsules. If we know the cost of a kilogram of API, we can then estimate the cost to produce a course of treatment, including a profit margin to the generic company to ensure sustainable high-quality supplies. The costs of formulating drugs, bottling and packaging are normally insignificant compared to the cost of producing the API. There are similar databases available for generic treatments produced in China.

2. For drugs not yet manufactured in India, analysis of the route of chemical synthesis, the raw materials used in the synthesis, and the yields from each step in this process can be used to estimate production costs. These estimation methods are more approximate, but have been shown to be reliable for estimating costs for Hepatitis C drugs, which are now being produced for prices similar to those predicted from analysis of chemical synthesis. ,

Implementation Project plan

Our proposal includes seven key stages. This project could be coordinated by a team of scientists in association with WHO, and would need an annual budget of at least $2 million. Results would be updated on a website and regular publications to show the costs of production of all important medicines.

1. Analyse the true costs of production for all drugs in the World Health Organization’s “Essential Medicines List”, and then supplement this with analysis of the top 50 selling treatments worldwide. The Essential Medicines List can exclude treatments because their comparative cost-effectiveness is insufficient, but the WHO does not always have access to information on the underlying costs of mass production, which can often predict cost-effective generic versions. These estimated prices should then be agreed and validated with the largest generic companies, as happened with antiretroviral treatment for HIV.

2. Re-analyse cost-effectiveness models to show which treatments could be introduced in low or middle income countries for mass treatment at prices close to the cost of production. At current published prices, many treatments may currently not be cost-effective for use in low or middle income countries. However this situation could change significantly if the true cost of production were used, with an appropriate royalty to the originator company if the drug is still on patent.

3. Organise meetings with national health authorities to educate them on the true costs of production of medicines, and then gain agreement on the potential to treat a range of diseases at the new low prices, based on revised cost-effectiveness analyses.

4. Publicise the results on the true costs of medicines when mass produced. In these results, the costs for producing generics could be compared with local prices. There are many examples of medicines being sold as generics, at prices far above their cost of production, even after expiry of the patent. For example, Sun Pharmaceuticals has just launched generic imatinib in the USA at the annual price of $47,000 versus $1775 in India for the same generic drug produced by the same company. Companies which change more than 5 times the cost of production for generics could be identified in a database and open-access website, covering the list of medicines in the EML and the Top 50 selling drugs.

5. Ensure that the quality and clinical efficacy and safety of generic mass produced drugs can be supported with published evidence. There is a widespread belief that generic drugs may be somehow inferior to those from originator companies, not bioequivalent, or even counterfeit. Bioequivalence data should be routinely published, together with clinical trials evaluating efficacy and safety outcomes on generic treatments. Currently it can be unclear which generic companies are producing high quality products, and results from quality controls and company audits for “Good Manufacturing Practice” need to be transparent.

6. When one drug in a group used to treat the same disease becomes generic, re-evaluate the cost-effectiveness of all other higher-priced drugs in the same class - their prices may no longer be justified. For example, the patents on several key treatments for HIV either have already expired or are about to expire.

7. Where a globally important drug or set of drugs is still far from patent expiry, set up a system of voluntary licensing to allow mass production of the treatment for use in low and middle-income countries, with royalties paid to the originator company.

Impact on public health
The public health benefits of expanded treatment access are potentially very large. One in three people do not have assured access to essential medicines worldwide, and in low income areas in Africa and Asia, only one half have access.

Depending on the number of diseases which could be successfully treated, there is the potential to save millions of lives each year.

• Potential impact in cancer treatment
Global cancer mortality was 8.2 million deaths per year in 2012 and is rapidly rising, with most disease burden lying occurring in low- and middle-income countries (LMICs). , Survival rates in LMICs are significantly worse than in high-income countries (HICs). However, a recent survey found that only 15% of patients in low and middle income countries in Southeast Asia have access to a standard set of cancer medicines.

• Potential impact in tuberculosis treatment
There were 9 million new cases of TB in 2013, of which 480,000 were multidrug-resistant (MDR-TB).(4) Treatment success rates are 86% for drug-sensitive TB, 48% for MDR-TB, and 22% for extensively drug-resistant TB (XDR-TB). While the FDA approved bedaquiline for the treatment of MDR-TB in 2012, fewer than 1,000 patients have been treated. Linezolid, a key drug for the treatment of XDR-TB, is sold by Pfizer at $68 per pill in South Africa, when a generic version is available through the Global Drug Facility at $6.90 a pill.

• Potential impact on treatment of diabetes
The global burden of diabetes is estimated at 347 million people. New oral diabetic control medicines are increasingly attracting interest from generic manufacturers, with recent cases of patent disputes heard in Indian courts. In Mozambique, Zambia, Mali, Nicaragua, Vietnam and Kyrgyzstan, the annual cost for insulin exceeds the average public sector pharmaceutical expenditure per person by a factor of 40.

Impact on human rights
It has repeatedly been affirmed that access to affordable medicines is an essential component to the human right to health. This system could ensure that people in a range of countries consistently have access to a wider range of treatments, and that their personal income is no longer a barrier to treatment access.

Evidence:
The references included in the bibliography show the methods used to estimate the minimum cost of treatment for Hepatitis B, Hepatitis C, certain cancers and Tuberculosis. The predictions of costs to treat Hepatitis C, originally made in 2013, have been shown to be reliable given recent sales prices for mass produced Hepatitis C treatments in India. In the past, similar predictions of the minimum cost of treating HIV have been shown to be reliable.

Bibliography and References

Key references on calculation of minimum costs of treatment:

Hill A, Gotham D, Cooke G, et al. Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries. J Virus Erad 2015;1:103–10

Hill A, Khoo S, Fortunak J, et al. Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries. Clin Infect Dis 2014;58:928–36. doi:10.1093/cid/ciu012

Hill A, Simmons B, Gotham D, Fortunak J. Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J Vir Erad 2016, 2: 28-31

Hill A, Gotham D, Fortunak J, Meldrum J, Erbacher I, Martin M et al. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment. Brit Med Jour Open 2016, 6: e009586

Hill A, Gotham D, Fortunak J et al. Target generic prices for mass production of novel treatments for tuberculosis. European AIDS Conference, Barcelona, Spain October 2015.



Main list of references, cited in text.

Hoen ET, Berger J, Calmy A, Moon S. Driving a decade of change: HIV/AIDS, patents and access to medicines for all. Journal of the International AIDS Society. 2011 Mar 27;14(1):15.

Untangling the web of price reductions. 17th ed. Geneva: Médicins sans Frontières [cited 2016 Feb 12]. Available from: http://www.msfaccess.org/sites/default/files/MSF_UTW_17th_Edition_4_b.pdf.

AIDS by the numbers 2015. Geneva: UNAIDS [cited 2016 Feb 12]. Available from: http://www.unaids.org/sites/default/files/media_asset/AIDS_by_the_numbers_2015_en.pdf

Amin, Tahir. Voluntary licensing practices in the pharmaceutical sector: An
acceptable solution to improving access to affordable medicines? 2007 Feb 8 [cited 2016 Feb 12]. Available from: http://static1.1.sqspcdn.com/static/f/129694/1099999/1192729231567/Oxfam+-+Voluntary+Licensing+Research+IMAK+Website.pdf?token=x%2FfhC2F0CHPzK7K22CdqEz9Uof4%3D

Hill A, Khoo S, Fortunak J, et al. Minimum costs for producing hepatitis C direct-acting antivirals for use in large-scale treatment access programs in developing countries. Clin Infect Dis 2014;58:928–36. doi:10.1093/cid/ciu012


Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57: 1333–42.

Van de Ven N, Fortunak J, Simmons B et al. Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus. Hepatology 2015; 61: 1174–1182.

Hill A, Simmons B, Gotham D, Fortunak J. Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J Vir Erad 2016, 2:28-31

Hill A, Gotham D, Fortunak J, Meldrum J, Erbacher I, Martin M et al. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment. Brit Med Jour Open 2016, 6: e009586

Hill A, Gotham D, Cooke G, et al. Analysis of minimum target prices for production of entecavir to treat hepatitis B in high- and low-income countries. J Virus Erad 2015;1:103–10

Med Guide India. Imatinib. 2016 [cited 2016 Feb 12]. Available from: http://www.medguideindia.com/find_brand_by_samepid.php?similarpid=1156,2641
Hardon A. New WHO leader should aim for equity and confront undue commercial influences. Lancet. 2003 Jan 4;361(9351):6. PubMed PMID: 12521037. Epub2003/01/11. eng.

Health Action International. Drug Policy at the 54th World Health Assembly: Increasing and Access to Essential Medicines. Amsterdam: Health Action International, 2001.

Cameron A, Ewen M, Ross-Degnan D, Ball D, Laing R. Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis. Lancet. 2009 Jan 17;373(9659):240-9. PubMed PMID: 19042012.

World Health Organization. WHO to address trade and pharmaceuticals. Geneva: World Health Organization, 1999.

Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. 2013. http://globocan.iarc.fr (accessed 1 Feb 2015).

Stewart BW, Wild CP, International Agency for Research on Cancer. World Cancer Report 2014. ISBN-13: 9789283204299
Economist Intelligence Unit. Breakaway: The global burden of cancer – challenges and opportunities. LIVESTRONG [online]. 2009:23. http://graphics.eiu.com/upload/eb/EIU_LIVESTRONG_Global_Cancer_Burden.pdf (accessed Jan 2016).

de Lopes GL. Issues in access to cancer medications in low- and middle-income countries. Cancer Control 2013 [cited 2016 Feb 12). Available from: http://cancercontrol.info/wp-content/uploads/2014/08/cc2013_24-26-Gilberto-NEW_2013.pdf

World Health Organization. Global tuberculosis report 2014. 2014. http://www.who.int/tb/publications/global_report/gtbr14_main_text.pdf. Accessed June 19, 2015.
PIH. PIH among Groups Bringing New TB Treatment to Those in Need. 2015. http://www.pih.org/press/pih-among-organizations-bringing-new-tb-treatment-to-those-in-need. Accessed June 18, 2015.

Under the Microscope. Geneva: Médicins sans Frontières [cited 2016 Feb 12]. Available from: http https://www.msfaccess.org/sites/default/files/MSF_TB_Report_UTM3rdEdition-2013.pdf

WHO. 10 facts about diabetes. Cited 2016 Feb 12. Available from: http://www.who.int/features/factfiles/diabetes/facts/en/

Subramanian, Balaji. Questionable Witnesses and Unquestionable Reasoning: Observations on Merck v. Glenmark. 2015 Oct 10 [cited 2016 Feb 12]. Available from: http://spicyip.com/2015/10/questionable-witnesses-and-unquestionable-reasoning-observations-on-merck-v-glenmark.html

Vishwanathan, Madhulika. Novartis sues Biocon over anti-diabetes drug vildagliptin: Bitter pill? 2014 Apr 13 [cited 2016 Feb 12]. Available from: http://spicyip.com/2014/04/novartis-sues-biocon-over-anti-diabetes-drug-vildagliptin-bitter-pill-2.html

Sinha, Anubha. SpicyIP Tidbit: Astrazeneca sues Glenmark for infringement of anti-diabetes drug Saxagliptin. 2014 Apr 8 [cited 2016 Feb 12]. Available from: http://spicyip.com/2014/04/spicyip-tidbit-astrazeneca-sues-glenmark-for-infringement-of-anti-diabetes-drug-saxagliptin.html

Beran D, Yudkin J, de Courten M. Access to care for patients with insulin-requiring diabetes in developing countries: case studies of Mozambique and Zambia. Diabetes Care. 2005;28(9):2136-40.

Hunt P; Report of the Special Rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health. United Nations General Assembly; 2008, A/63/263.

Chandni Raina, Centre for WTO Studies, Indian Institute of Foreign Trade_B

Submission: Centre for WTO Studies, Indian Institute of Foreign Trade
Prepared by: Chandni Raina
Country: India

Abstract

UN Working Group on Access to Medicines identified six barriers to access to medicines in resource-poor countries (MDG Gap Task Force, 2008). One of the barriers was the Trade Related Intellectual Property Rights (TRIPS). With TRIPS Plus nature of FTAs/RTAs, the policy incoherence between trade and access to medicines and health and therefore human rights has become severe. The question is what role can the UN play in this discourse when this is largely being negotiated between nation states with presumably some understanding of the impact TRIP Plus provisions are likely to have. However, it is important to keep in mind that the UN has the responsibility to ensure policy coherence between human right issues connected with access to medicines and trade in case the latter impinges upon the former in an adverse manner. The intervention being suggested is at the policy level to seek preservation of TRIPS flexibilities, mandating WHO and WIPO to intensify efforts to create capacities among countries to examine TRIPS Plus issues and to understand their implications and interventions to bring in greater accountability of arbitration bodies.

Submission

A. Rationale of the submission
The conclusion of the Agreement on Trade Related Intellectual Property Rights (TRIPS) in 1995 brought in its wake a complete overhaul in the level of protection required to be provided by the members to the Agreement. At the same time, it allowed countries the policy space to adapt to the minimum norms set while crafting a legal framework that reflected their level of development and addressed public policy concerns on technology transfer, protection of public health and other sectors of vital importance. This flexibility or policy space is now being sought to be curtailed through Regional/Free Trade Agreements. Most IPR chapters in bilateral FTA/RTAs do this by:

a) Seeking compliance with Multilateral Agreements that post date the TRIPS- thereby opening the member States of the bilateral/regional arrangement to provide protection beyond TRIPS (thus raising the minimum standards set by the latter). Equally important is the fact that compliance with hitherto independent Agreements can then be enforced through the dispute settlement mechanism of the concerned bilateral or regional trading agreements.

b) Address areas where the TRIPS Agreement was silent with a view to reduce flexibility. This has been seen in the way provisions relating to patentability criteria and protection of undisclosed information are being developed. The objective of this exercise is to reduce the flexibility available to countries to define these terms and implement the provisions in a manner that best suits their condition.

c) Enhance enforcement by delineating what action could be taken by judicial authorities; seeking criminal enforcement for actions that were until now only amenable to civil procedures such as trade secret theft; and by seeking statutory damages for all offenses and possibility to impose exemplary damages. Border measures are another very critical area where ‘in transit’ measures, ex-officio action and border enforcement for all rights including patents and designs are sought. FTAs/RTAs seek to remove the safeguards and checks and balances so sacrosanct in the TRIPS provisions.

These agreements are seeking to curb the flexibility and reduce the ability of member States to address concerns. While this can impact an economy in many ways it substantively affects drug prices and access to medicines. An Oxfam study on the impact of US Jordan FTA indicates that intellectual property rules adopted led to a delay in the entry of generic competition and access to medicines was seriously jeopardized with prices increasing considerably. Similarly other research studies bring out the inappropriateness of developed countries negotiating TRIPS Plus provisions in FTAs and the impact this has on access to medicines.

B. Model to Address this Policy Incoherence
Four international human rights treaties and declarations collectively known as “International Bills of Human Rights’ namely the: The United Nations Charter, Universal Declaration of Human Rights (UDHRs), International Covenant on Civil & Political Rights (ICCPRs), International Covenant on Economic, Social and Cultural Rights (ICESCRs) have provisions on ensuring health for all and on access to medicines.

UN Working Group on Access to Medicines identified six barriers to access to medicines in resource-poor countries (MDG Gap Task Force, 2008). One of the barriers was the Trade Related Intellectual Property Rights (TRIPS). With TRIPS Plus nature of FTAs/RTAs, the policy incoherence between trade and access to medicines and health and therefore human rights has become severe.

The question is what role can the UN play in this discourse when this is largely being negotiated between nation states with presumably some understanding of the impact TRIP Plus provisions are likely to have. However, it is important to keep in mind that the UN has the responsibility to ensure policy coherence between human right issues connected with access to medicines and trade in case the latter impinges upon the former in an adverse manner. The intervention being suggested is at the policy level to seek preservation of TRIPS flexibilities, mandating WHO and WIPO to intensify efforts to create capacities among countries to examine TRIPS Plus issues and to understand their implications and interventions to bring in greater accountability of arbitration bodies.

C. Mechanism for Implementation

The model being suggested is more at the policy level and has three legs:

a. Foremost among all is a UN Resolution on the need to preserve TRIPS flexibility while negotiating RTAs/FTAs. The resolution should ideally identify the policy spaces available to countries under the TRIPS Agreement and the impact on access to medicines of giving up these flexibilities or adopting a tighter regime. The resolution should not be just limited to use of compulsory license.

b. UN Specialized agencies such as the World Health Organization (WHO) and the World Intellectual Property Organization (WIPO) must work more intensively towards preserving TRIPS Flexibilities while advising LDCs on the amendments required to their law. The impact of going beyond TRIPS or accepting TRIPS Plus commitments must also be clearly brought out in their policy documents used for dissemination among developing countries and LDCs. Capacities need to be build among developing countries and LDCs on this issue.

c. Unlike under the TRIPS Agreement, disputes arising from the FTAs/RTAs go through opaque arbitration mechanisms which have no appeal. It is important that the UN set down guiding principles for the arbitrators on the manner in which provisions of FTAs and their compliance should be interpreted especially when it comes to access to medicine issues, public health matters or a decisions concerning sectors of vital importance to the said economy. The principles should clearly bring out the due weightage that needs to be given to policy concerns, public health measures taken by Governments and broader national interest when examining such cases.

d. From the UN, there should be a call for reforming the private arbitration bodies with a view to enhance transparency, address conflict of interest and build greater consistency in decisions while also seeking a mechanism for appeal.

D. Manner in which the Suggestion impacts Innovation, Public health, Human Rights and Trade

i) Impact on Innovation
TRIPS Agreement was negotiated with the objective of promoting technological innovation, enabling transfer and dissemination of technology to the mutual advantage of producers and users of technological knowledge. The RTAs/FTAs are bringing about a paradigm shift by disincentivizing path breaking medical research and development of technologies.
The above proposal seeks to ensure that the TRIPS Agreement is complied with in letter and spirit and the flexibilities under the Agreement are utilised to model regimes that address the ground realities of the respective countries. This in turn will impact innovation and dissemination of technologies in a positive manner.


ii) Impact on Access to Medicines and Public Health
The steps suggested will strengthen the hands of the developing countries and LDCs in preserving TRIPS flexibilities in RTAs/FTAs. The mandate to WHO and WIPO will build capacities among the developing countries and LDCs to duly take into account the impact IPR provisions in trading agreements can have on their ability to address public health problems. It is also important to inform the developing countries and LDCs that bilateral agreement involving TRIPS Plus provisions are likely to create uncertainty and lead to fragmentation of the market making it difficult for generic competition to enter.
Guidance to arbitration bodies from the UN that public health measures and broader national interest are perfectly legitimate and cannot be overlooked will be important to at least place issues in perspective while deciding cases brought up by private companies against a State.
iii) Impact on Human rights
The model seeks to protect and nurture innovation while creating capacities among countries to examine the impact of their decisions, improve the understanding among the arbitrators on matters that concern public interest and create public opinion on TRIPS Plus issues. It would therefore impact the Sustainable Development Goal No. 3 on promoting health for all positively. The proposal will directly impact three targets set to be achieved by 2030 - ie-
• Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries, provide access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS Agreement and Public Health, which affirms the right of developing countries to use to the full the provisions in the Agreement on Trade Related Aspects of Intellectual Property Rights regarding flexibilities to protect public health, and, in particular, provide access to medicines for all
• To end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases
• To reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being
while also impacting the others indirectly.
iv) Impact on Trade
The TRIPS Agreement was negotiated to reduce distortions and impediments in international trade while promoting effective and adequate protection of intellectual property rights. It was to ensure that measures and procedures to enforce intellectual property rights do not themselves become a barrier to legitimate trade. The bilateral trade agreements are seeking to tighten this framework to the advantage of the innovators and therefore create a misbalance between the users and creators of intellectual property. TRIPS Plus measures in bilateral trading arrangements will lead to uncertainty and evergreening of protection which in turn will impact competition and trade adversely. It is important that the balance be realigned to promote trade.

Bibliography and References

Text of the Trans-Pacific Partnership Agreement on https://ustr.gov/trade-agreements/.../trans-pacific-partnership/tpp-full-text; Leaked text of India EU FTA on Knowledge Ecology International. http://keionline.org/node/1681

All costs, no benefits: How TRIPS-plus intellectual property rules in the US-Jordan FTA affect access to medicines, Oxfam Briefing Paper, March 2007

The High Price of “Free” Trade: U.S. Trade Agreements and Access to Medicines Ruth Lopert and Deborah Gleeson in the Journal of Law, Medicine and Ethics (Vol 41, Issue 1, Pages 199-223, Spring 2013),

B. Kiliç and P. Maybarduk, “Comparative Analysis of the United States’ TPFTA Intellectual Property Proposal and Vietnamese Law,” Public Citizen, 2011, available at (last visited February 19, 2013);

B. Kiliç and P. Maybarduk, “Comparative Analysis of the United States’ TPFTA Intellectual Property Proposal and Malaysian Law,” Public Citizen, September 2011 (Updated December 2011), available at (last visited February 19, 2013)

Public Citizen, “Comparative Analysis of the U.S. Intellectual Property Proposal and Peruvian Law, 2011,” available at (last visited February 19, 2013)

B.Kiliç and P. Maybarduk, “Comparative Analysis of the United States’ TPPA Intellectual Property Proposal and Chilean Law,” Public Citizen, April 2012, available at (last visited February 19, 2013).

Chandni Raina, “TPP’s all about the health of Big Pharma”, Financial Express 10th February 2016

Luc Besançon and Zuzana Kusynová, International Pharmaceutical Federation

Submission by: Luc Besançon and Zuzana Kusynová
Organization: International Pharmaceutical Federation (FIP)
Country: The Netherlands

Abstract

Access to effective medicines is crucial for successful prevention and treatment; therefore, it should be a basic human right.
Research and development (R&D) models are turning towards transparency and public support, through the sharing of information, capabilities, and intellectual property (IP), including between competitors. Models as ‘open innovation’ should involve partners from developing countries to participate at the research, as their knowledge of the environment can identify and meet the concrete access needs in these countries. The integration of medicine use considerations in earlier stages of R&D is crucial.

Pharmaceutical sciences are key for innovation and access to new medicines and technologies. In its recent publications, FIP reviewed the achievement and impact of the large spectrum of pharmaceutical sciences over the last 50 years, and identified the major challenges for the pharmaceutical sciences in the next 5 – 10 years. Pharmaceutical sciences enhance all aspects of R&D important for improved access, including those suitable for low resource setting: maximising the lifetime of a medicine, reducing phases for R&D of generics (e.g. biowaivers), using predictive computer simulations and systems pharmacology models, building know-how for development and assessment of generics for treatment of NCDs, developing easy administration routes, etc.

Economic models and incentives, such as EU-sponsored Innovative Medicines Initiative (IMI), collaboration between the United Nations Population Fund (UNFPA) and the Institute for Pharmaceutical Sciences (MIPS) at Monash University, etc. stimulate R&D.
Access to medicines is impaired by non-affordability, lack of education on health, and shortage of trained healthcare personnel. Pharmacy organisations, both national and international, promote to governments and other stakeholders, the need to take effective action to improve policy, practice, science and education in relation to access to medicines. There is a wide range of technical expertise amongst pharmaceutical scientists and pharmacists worldwide that can be mobilised for this purpose.

Submission

ACCESS TO MEDICINES AS A HUMAN RIGHT
Medicines are crucial for successful prevention and treatment of many illnesses. Access to effective medicines should, therefore, be considered to be a basic human right. However, one-third of the world’s population lacks access to essential medicines. In the poorest parts of Africa and Asia, this figure rises to one-half of the population. [1]

COMPLEXITY OF ACCESS
Access to medicines is complex and has been described by the World Health Organization (WHO) as having four main components: rational selection, affordable prices, sustainable financing and reliable systems for purchase, storage, and distribution. Non-affordability, lack of education on health, weak public distribution systems for medicines and shortage of trained healthcare personnel, all adversely affect the ability to access medicines in developing countries. [1]

Pharmacy organisations, both national and international, have a vital role to play in taking responsibility for promoting, to governments and other stakeholders, the need to take effective action to improve policy and practice in relation to access to medicines. There is a wide range of technical expertise amongst pharmacists worldwide that can be mobilised for this purpose. [1]

As the focus of the High-Level Panel is on research, development, and innovation, emphasis will be given to these aspects.

INNOVATIVE R&D MODELS
Developing a new medicine involves a great deal of time, effort, scientific research and expense. Unfortunately, the traditional closed R&D business model has been failing to generate optimal results and bears a high risk. Consequently, R&D is now turning towards new approaches that aim to enhance transparency and attain broad (public) support of medicine development through the sharing of information, capabilities, and intellectual property (IP) between organisations, including competitors. Unlike more traditional collaboration models, this approach can also allow collaborators to exploit a new technology in other, non-competing areas. [2] Moreover, open innovation involves more partners, including from developing countries, to participate at the research. Since they are familiar with the situation and the needs of the developing countries, they can for example integrate the concrete considerations such as medicine use and administration in earlier stages of R&D. This can directly improve the access to the medicine once it reaches the market.

PHARMACEUTICAL SCIENCES ARE KEY FOR INNOVATION AND ACCESS TO NEW MEDICINES AND TECHNOLOGIES
In 2012 FIP looked back over the last 50 years in reviewing the achievements and impact of the pharmaceutical sciences over the spectrum of its activities, including drug discovery, drug absorption, distribution, metabolism and excretion, pharmacokinetics and pharmacodynamics, formulation science and drug regulation. [3] This review accompanied an outline of how the pharmaceutical sciences might look in 2020 [4], and identified the major research activities which are likely going to drive drug discovery and development, as well as the enabling technologies, together with the paradigm shifts foreseen in drug discovery, development. This analysis also lead to the development of scenarios analysis on the evolution of pharmaceutical sciences. [5] More recently, an FIP position paper has been published also looking forward, specifically identifying the major challenges for the pharmaceutical sciences in the next 5 – 10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science. [5]

INNOVATIVE SOLUTIONS ARE NEEDED FOR LOW-PROFIT AREAS
There is often a disconnection between the value, price and cost of medicines, and real outcomes should be measured in terms of lives saved and public health needs. For example, the emerging global health threat of antimicrobial resistance (AMR) leading to significant gaps in the treatment of infectious diseases is calling for the R&D of new medicines. However, for a number of reasons including financial ones, the development of antimicrobial, including antibiotics and other anti-bacterial agents, has not been fully recognised by the pharmaceutical industry as a priority area. Indeed, only two types of new antimicrobials (oxazolidinones and lipopeptides) have come to market over the past 30 years. [6] Any compound in the pipeline is likely to generate low profit, at least initially, because of limited use as a last-ditch treatment. As a consequence of this failure in development, there is an urgent need to ensure economic incentives combined with innovative R&D initiatives to stimulate interest in new antimicrobials. [7] This includes the development of alternative economic and pricing models, the refinement of public-private partnerships with open access to relevant information across national borders, and, in common with all aspects of drug development, a strict oversee of data integrity and scientific honesty. [5]

PATENT POLICY
The revision of patent policy in order to make it more flexible could help to resolve the conflict between the profit motives of companies and the public interest in maintaining the effectiveness of antimicrobial therapy. Collective action with involvement of all stakeholders, including those representing pharmaceutical expertise, is necessary, as exemplified by the multilateral initiative on malaria research. [8, 9, 10] In line with SDG 3b, the provision of Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) already includes some flexibility in intellectual property (IP) regulation, allowing greater scope for countries to accommodate their own patent and intellectual property systems and developmental needs. This should go some way to de-linking R&D costs from price to be paid by health care systems. [11]

PUBLIC-PRIVATE INITIATIVES AND INCENTIVES
There are successful examples of initiatives that aim to tackle bottlenecks in R&D in addressing high-priority healthcare needs, while improving the drug development process through more efficient discovery to develop better and safer medicines for patients. [12]
The world’s largest public-private partnership in health, called The Innovative Medicines Initiative (IMI), seeks to accelerate the development of better and safe medicines for patients. IMI is a joint undertaking between the European Union and the pharmaceutical industry association EFPIA. [12] With a total budget of €2 billion – €1 billion each from the European Union and the pharmaceutical industry through EFPIA, it brings together European stakeholders to pool their resources and knowledge in a collaborative effort to address some of our most pressing and complex health issues. Set up in 2008, IMI is currently overseeing some 40 projects, dealing with issues from superbugs to cancer. The initiative is already delivering results, covering early to late stages of medicines development from biomarkers for vaccine safety to understanding chronic pain and developing anti-tuberculosis drug combinations. [12]
Collaboration is pursued within IMI by sharing data, pooling resources, and exchanging expertise, and the model should be applied more widely. [12]
IMI also includes considerations to the education of current and future pharmaceutical scientists. This is very much aligned with the SDG 9.5 to “Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries, in particular developing countries, including, by 2030, encouraging innovation and substantially increasing the number of research and development workers per 1 million people and public and private research and development spending.” Within this objective, it would be reasonable to include a sub-objectives specifically focusing on pharmaceutical scientists, so that the efforts made to reach SDG 9.5 would also lead to increased capacity in R&D in the field of health, ultimately supporting the achievement of the SDG this High-level panel is focusing on. Indeed, meeting these goals require not only a sufficient but also competent pharmaceutical sciences workforce. To reach this dual objective, FIP has set an ambitious 2 million USD programme called FIPEd to facilitate the reform of pharmacy and pharmaceutical sciences education based on locally determined needs.[13]

RESEARCH TO ENHANCE ACCESS TO EXISTING PRODUCTS
The injectable uterotonic, oxytocin, is a MNCH (maternal, newborn and child health) life-saving medicine for post-partum bleeding. Because it needs cold storage, the access to this medicine can be limited especially in lower income countries. In this context, FIP has served as a facilitator in the collaboration between the United Nations Population Fund (UNFPA) and the Institute for Pharmaceutical Sciences (MIPS) at Monash University in measuring the impact of disruption of cold storage on the safety and efficacy of injection of oxytocin. The objective was to maximise the lifetime of this medicine in developing better storage conditions in the presence of elevated temperatures. Clearly, if a product has a longer expiry date this will improve access to it, in turn improving MNCH as outlined in SDG 3. This example illustrates how research can have an impact on accessibility of existing pharmaceutical products.

BIOWAIVERS
Innovative ways should also be considered to reduce the costs and time of the development of a new medicine and its generic versions. For example, for over a decade, FIP has been working in collaboration with the World Health Organization on the concept of biowaivers, so that the in-vivo tests of bioequivalence can be waived based on dissolution tests. The application of this concept enables to preserve the safety of drugs approval while minimising the need for full in vivo or clinical investigation.

The FIP Special Interest Group on Regulatory Sciences is stimulating the development of this approach through the publication of biowaiver monographs (over 40 to date) based on literature reviews. Issues discussed in these reviews include solubility and permeability, dissolution of dosage forms, pharmacokinetics, the therapeutic use and therapeutic window of the API, data on excipient interactions and problems with bioavailability and/or bioequivalence. This project is supported by WHO and takes published guidance from WHO, FDA and EMA into consideration as well as scientific developments in this field. The collected information is critically reviewed, published in the Journal of Pharmaceutical Sciences and made available on the FIP Website (http://www.fip.org/bcs). Although the monographs have no formal regulatory status, they are accepted by medicines regulatory agencies for drug approval as they represent the best scientific opinion currently available and, as such, facilitate the availability of cheaper medicine alternatives, thereby enhancing access. [14]

ORAL ADMINISTRATION OF MEDICINES TO REMOVE BOTTLENECKS TO ACCESS
The easiest way to administer a drug is by the oral route as a tablets or capsule. However, designing these pharmaceutical products in such a way that the active ingredient is absorbed at an appropriate rate and to an appropriate extent from the gut is far from easy. More research needs to be done in this regard, to facilitate access to medicines especially in low resource settings.
The ORBITO project, [15] sponsored by the EU, is an example of a collaborative approach between academia and industry to facilitate understanding of the many factors that affect the absorption of medicines from the human gastrointestinal tract. New experimental methods and approaches using predictive computer simulation are being evaluated using the extensive data based available in the pharmaceutical industry. Crucially, the project will set up a framework to guide the use of these new tools in drug development. Several members of the FIP Special Interest Group on Regulatory Sciences participate in this important European initiative to streamline pharmaceutical development.

SYSTEMS PHARMACOLOGY MODELS
Systems pharmacology seeks to develop quantitative computational models that integrate discrete pieces of data on biomolecules, organelles, cells and tissues to predict therapeutic and toxic effects of medicines, thereby guiding the development of new medicines in making critical decisions. Importantly, it is a bridge between greater understanding of disease mechanisms and therapy and in vitro and in vivo investigation. Best practices are now in the process of elaboration. [5]

DEVELOPMENT OF GENERIC PRODUCTS FOR BIOLOGICAL PRODUCTS
The advent of patent expiry on biological drugs poses the question as to what the impact on access to these medicines will be. Central to this issue is the concept of comparability, requiring the demonstration that 2 products of the same biologic are essentially similar with regard to efficacy and safety (and quality). Comparability is usually assessed during the development of a new biological drug and also needs to be considered with regard to the demonstration of the biosimilarity of generic and reference products. However, it is widely acknowledged that current comparability techniques are not capable of characterizing biological products completely. Accordingly, the continuing challenge is to progress this assessment in preclinical evaluation involving the development of better methods to characterise the content of different products of the same compound and relevant pharmacokinetic studies in appropriate animal species. [5] In this context, access to these medicines and their biosimilars needs to be looked at not only from the IP point of view, but also from a know-how perspective.

UHC via RESPONSIBLE USE OF MEDICINES
We will not expand on the important issue of improved access and universal health coverage via responsible use of medicines, as it is not included in the focus. But we would like to stress on the fact that while many resources are invested in the development of new medicines, the issue of responsible use of medicines is crucial to ensure that the full value of these new medicines are made available to patients.


ABOUT THIS CONTRIBUTION:
Founded in 1912, the International Pharmaceutical Federation (FIP) is the global organization gathering 137 national associations of pharmacists and pharmaceutical scientists. FIP represents 3 million pharmacists and pharmaceutical scientists and in an NGO in official relations with the World Health Organization (WHO).

While this contribution has been prepared by Luc Besançon and Zuzana Kusynová, it is based on the inputs from many experts who are members of FIP.

Bibliography and References

[1] International Pharmaceutical Federation (FIP). FIP Statement of Policy on Improving Access to Medicines in Developing Countries. Cairo, 2005. [cited 2016 February 12]. Available from: http://www.fip.org/statements

[2] Deloitte. Executing an Innovation Model: Cooperation is key to competition for biopharmaceutical companies. [Online]. 2015. [cited 2016 February 12]. Available from: https://www2.deloitte.com/content/dam/Deloitte/us/Documents/life-sciences-health-care/us-lshc-open-innovation.pdf

[3] Rowland M, Noe CR, Smith DA, Tucker GT, Crommelin DJ, Peck CC, Rocci ML Jr, Besançon L, Shah VP. Impact of the pharmaceutical sciences on health care: a reflection over the past 50 years. J Pharm Sci. 2012 Nov;101(11):4075-99. doi: 10.1002/jps.23295. Epub 2012 Aug 21.

[4] Shah VP1, Besancon LJ, Stolk P, Tucker G, Crommelin DJ. The pharmaceutical sciences in 2020: report of a conference organized by the board of pharmaceutical sciences of the International Pharmaceutical Federation (FIP). Pharm Res. 2010 Mar;27(3):396-9. doi: 10.1007/s11095-009-0048-3. Epub 2010 Jan 27.

[5] Crommelin D, Stolk P, Besançon L, Shah V, Midha K, Leufkens H. Pharmaceutical sciences in 2020. Nat Rev Drug Discov. 2010 Feb;9(2):99-100. doi: 10.1038/nrd3087.

[6] Tucker G. et al. Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective. 2015. Journal of Pharmaceutical Sciences. [cited 2016 February 12]. doi:10.1016/j.xphs.2015.12.001 Available from: http://www.sciencedirect.com/science/article/pii/S0022354915001811

[7] European Medicines Agency (EMA) and European Centre for Disease Surveillance in Europe (ECDC). The Bacterial Challenge: Time to React. [Online]; 2009 [cited 2016 February 12]. Available from: http://bit.ly/1JuxvlT

[8] Harrison PF, Lederberg J. The National Academy Press, Open Book: Antimicrobial resistance: Issues and Options. [Online]; 1998 [cited 2016 February 12]. Available from: http://bit.ly/1Mxd5KS.

[9] Ramanah L, Powers JH. Antibacterial R&D incentives. Nature reviews- Drug Discovery. 2011 October; 10.

[10] Butler D. Time to put malaria control on the global agenda. Natura. 1997; 386: p. 535-6.

[11] Buse K, Walt G. Global-public private partnerships: Part II. Bulletin of the World Health Organization. 2000; 78: p. 699-709.

[12] Report of the Consultative Expert Working Group on Research and Development: Financing and Coordination, April 2012, WHO. Geneva. [cited 2016 February 12]. Available from: http://www.who.int/phi/cewg/en/

[13] The Innovative Medicines Initiative (IMI). [Website]. 2016 [cited 2016 February 12]. Available from: http://imi.efpia.eu/achievements

[14] FIP Education Initiative. More information and publications: http://www.fip.org/educationreports

[15] International Pharmaceutical Federation. Biowaver monographs 2004-2012: Bringing essential medicines to those who need them most. The Hague, the Netherlands: International Pharmaceutical Federation, 2012. [cited 2016 February 12]. Available from: http://www.fip.org/centennial/files/static/press/FIP_centennialbook_biowaiver_webversion.pdf [15] Project Orbito. [Website]. 2016 [cited 2016 February 12]. Available from: http://www.orbitoproject.eu/

Santosh Kumar Mishra, SNDT Women's University

Submission by: Santosh Kumar Mishra
Organization: SNDT Women's University
Country: India

Abstract

Innovation, Research and Technology for Improving Sustainable Health and Care System All Ensuring healthy lives and promoting the well-being for all at all ages is essential to sustainable development. Significant strides have been made in increasing life expectancy and reducing some of the common killers associated with child and maternal mortality. Major progress has been made on increasing access to clean water and sanitation, reducing malaria, tuberculosis, polio and the spread of HIV/AIDS. However, many more efforts are needed to fully eradicate a wide range of diseases and address many different persistent and emerging health issues. It is in this context that the Sustainable Development Goal (SDG)-3 emphasizes: “ensure healthy lives and promote well-being for all at all ages”. In order to achieve this goal, it is essential that the health and care system routinely uses innovation, technology, and research and development (R&D). Sound sustainable development policy and practice is embedded across the system generating more value from the available financial, environmental and social resources. Innovative approaches should be systematically encouraged and the spread of good practice and wider adoption significantly accelerated. Nevertheless, there are several challenges in caring for a changing population with limited resources. This paper aims to address issues related to gaps in research and barriers to innovation and implementation. The importance of empowering patients and the public through technology for the future plan of the health system has also been looked into. In terms of methodology employed in this presentation, secondary data (which are primarily qualitative in nature) have been used and they have been analyzed using descriptive research method. The paper concludes that innovation to reduce environmental impact, enhance social value, reduce cost and improve quality of care is an integral part of the planning, development and delivery of services.

Key Words: Innovation, Research and Development (R&D), Technology, Sustainable Development Goal (SDG), and Sustainable Health.

Submission

Innovation, Research and Technology for Improving Sustainable Health and Care System All

1. Introduction:
Health is fundamental to human development. All people, regardless of social status, consistently rank good health as a top priority, and healthy people are critical to sustaining societies (John Helliwell, Richard Layard and Jeffrey Sachs, 2012). Ensuring healthy lives and promoting the well-being for all at all ages is essential to sustainable development. Significant strides have been made in increasing life expectancy and reducing some of the common killers associated with child and maternal mortality. Major progress has been made on increasing access to clean water and sanitation, reducing malaria, tuberculosis, polio and the spread of HIV/AIDS (World Organization of the Scout Movement, 2016). However, many more efforts are needed to fully eradicate a wide range of diseases and address many different persistent and emerging health issues. It is in this context that the Sustainable Development Goal (SDG)-3 emphasizes: “ensure healthy lives and promote well-being for all at all ages”. In order to achieve this goal, it is essential that the health and care system routinely uses innovation, technology, and research and development (R&D). Technology has the power to improve access to health care services (Karten Taylor, 2015). Sound sustainable development policy and practice is embedded across the system generating more value from the available financial, environmental and social resources. Innovative approaches should be systematically encouraged and the spread of good practice and wider adoption significantly accelerated (Sustainable Development Unit, 2015). Nevertheless, there are several challenges in caring for a changing population with limited resources.

2. Objectives and Methodology Employed:
This paper aims to address issues related to gaps in research and barriers to innovation and implementation. The importance of empowering patients and the public through technology for the future plan of the health system has also been looked into. In terms of methodology employed in this presentation, secondary data (which are primarily qualitative in nature) have been used and they have been analyzed using descriptive research method.

3. Impact on Remedying Policy Incoherence:
The healthcare industry has experienced a proliferation of innovations aimed at enhancing life expectancy, quality of life, diagnostic and treatment options, as well as the efficiency and cost effectiveness of the healthcare system. Information technology has played a vital role in the innovation of healthcare systems. Despite the surge in innovation, theoretical research on the art and science of healthcare innovation has been limited. One of the driving forces in research is a conceptual framework that provides researchers with the foundation upon which their studies are built (Vincent K. Omachonu and Norman G. Einspruch, 2010).

4. Impact on Public Health:
Good public health ensures an efficient work force. Organizations can ensure a prominent position on the global stage by staying on the leading edge of technological development. Public health and technological innovation are vital elements of prosperous economies. It is important to understand how these elements affect each other (Preetinder Singh Gill, 2013). New technologies have the potential to extend the reach of health professionals while improving quality and efficiency and reducing costs.

5. Impact on Human Rights:
Too often, governments neglect the health of the world’s most marginalized people. And yet it is these very people – such as women, the poor, people engaged in the sex trade, men who have sex with men, migrants and refugees, drug users and prisoners – who are most affected by disease and poor health. World’s most serious epidemics and health challenges cannot be successfully addressed unless the rights of these communities to health care are protected and health programs are designed to meet their specific needs. Thus, innovation, research and technology in public health are linked with human rights in many ways. Violations of human rights can have serious health consequences; unfairly administered health policies or programs can violate human rights. Protecting human rights can reduce individuals' vulnerability to ill health and its effects (Mary Whisner, 2015).

6. Implementation:
Public health has been a priority for global action for many years. The right of everyone to the enjoyment of the highest attainable standard of physical and mental health is a universal human right, just as the burden of disease is shared by all humanity. The constitution of the World Health Organization (WHO) underscores that achievements by any state in the promotion and protection of health are of value to all. In the age of globalization, progress made in public health in one country has an impact on the international community as a whole. Consequently, a compelling case can be made for effective international cooperation in public health, and such cooperation is an essential foundation for sustainable development.
Public health and medical technologies are an important focus of the international system, including in the system-wide work of the United Nations – most notably in the Millennium Development Goals (MDGs). The very founding objective of the WHO is the attainment by all peoples of the highest possible level of health (World Health Organization, World Intellectual Property Organization and World Trade Organization, 2013).

For the purpose of implementation, vision should be: “a health and care system where innovation, technology, and research and development (R&D) are routinely used to improve health and care by ensuring environmental and social sustainability” (Sustainable Development Unit, 2015). Innovative approaches should be systematically encouraged and the spread of good practice and wider adoption should be significantly accelerated. Further, a more sustainable health and care system should harness three important opportunities: Innovation, Technology and R&D; particularly where they act as catalysts for each other and the rest of the system. Brief description of these three key terms (Innovation, Technology, and R&D) in the context of sustainable health is presented below:
o Innovation: Innovation means using existing and new knowledge, techniques and technologies more creatively, systematically and ambitiously, to improve health outcomes. It means rapidly implementing what is known to work so that it becomes the norm. Sustainability needs to be a core dimension of the quality agenda and, like any area of quality improvement, should accelerate the spread and adoption of improved policies and practices that deliver better outcomes within environmental limits. Innovation is a natural part of sustainability and should not always be considered complex or expensive.

o Technology: Technology refers to the collection of tools, processes, interventions and procedures used to improve health by professionals, and increasingly by patients and the public. This includes drugs, guidelines, decision support, near patient diagnostic and monitoring equipment, used not just by health professionals but also by patients, carers, and the public. Technology has the power to transform health and wellbeing by improving how the health and care system interacts with patients, service users and communities. It supports how information and control are shared, how health and illness are monitored, and how interventions are delivered and judged to be effective or otherwise. Empowering patients and public to take much more control over their own care and treatment is a key principle. “Tele-health”, for example, has huge potential to give people much more understanding and control over how their own health is shaped and their care is provided. Technologies significantly affect (and often improve) our ability to understand, protect, control and improve our health and the environmental, social and political causes of health. Sustainable technologies can save money, reduce waste and pollution, and improve the care environment (David Pencheon and Sonia Roschnik, 2015).

o Research and development (R&D): Research is central to understanding the more systematic use of scientific and technological advances to improve prevention, care and outcomes. This includes changing behaviours, more effective forms of governance and use of resources, and better ways of developing future proof policies. This needs to match the stark picture that research has already generated about the unsustainability of the ways in which we define our health, live our lives, protect our families and communities, and organize our care. The traditional model of research in health and care has largely followed a medical model using a predominantly technocratic and problem solving approach: identify the problem and its cause and implement the “technical solution”. A more diverse and integrated set of research approaches will be needed to manage a safe and secure transition to a sustainable future.

The health and care system has never benefitted from so many technological and social opportunities whilst facing so many emerging environmental and financial challenges. The rate of increase in new research and technology is outstripping capacity to implement and innovate to improve health outcomes. We risk over-dependence on historical research, implementation techniques, and attitudes, whilst forgetting that the core values of the health and care system should support better research implementation and innovation that will help address the future fairly, and sustainably. Failing to harness the opportunities of better integrated research and innovation means we also fail to improve the system at the scale and pace that is demanded by service users and the public, needed by the science and required by the law.

The following themes highlight three areas where progress can be made:
(a) Using what we know now: Many effective ways to reduce carbon emissions and improve outcomes already exist. However, these interventions need to be implemented more widely, more ambitiously and more innovatively across the whole system now. For instance, phasing out ineffective, inefficient and inconvenient interventions and models of care, helping improve lifestyles and community resilience, reducing waste, investing in renewables and recycling all add both financial and social value into ways of working. The actions that are evidenced and need to be more widely adopted everywhere now are summarized below:

• Decarbonise estate, energy, and beyond: First we need to reduce demand for energy particularly by designing estate and infrastructure around systems of prevention and care, not vice versa. Secondly, we should ensure the very highest efficiency in the ways we use energy everywhere. Thirdly the health and care system needs to be highly visible investors in renewable energy giving both the energy markets and the public confidence that, this is a crucial action needed for a sustainable energy system.
• Invest in flexible, adaptable and resilient infrastructure: Sustainable and cost effective use of health system resources depends on a much more flexible approach to physical resources. This means using buildings to their maximum potential and not limiting their use to one purpose and for only some of the time. This principle also applies to the human resources within the health system, with a much more flexible approach to skill mix to address needs and develop personal and community assets. For instance, we need to increase resilience across the system by adapting models of care in specific settings.
• Reduce waste: The most effective way to reduce waste is to ensure, where possible, preventable conditions are prevented. This involves using the best research consistently to stop all ineffective, unnecessary and unsustainable interventions (“reducing over diagnosis” and “over treatment”). We should make use of alternative interventions that improve the experience and outcomes for people such as better technology, supported self-care closer to home and better models of care.

(b) Innovative models of care: New technology, new methods of co-operation and novel business models are already exploiting the significant potential to improve health. The power of technology needs to be harnessed to connect people and organizations better in order to protect and improve health. The explosion of new technology is advancing as rapidly in the hands of the public as those of large organizations, enabling different models of health protection, improvement and care. Similarly, better ways of helping people design their own models of care can significantly increase outcomes with fewer environmental consequences with reduced cost. For instance, using multi-disciplinary teams across organizations to design and deliver mental health services in the community can help support people to stay healthy and avoid the need for hospital care. Breaking down barriers between organizations has been recognized as a crucial opportunity to improve care for people using services.

(c) Interdisciplinary research: Integrating research from different disciplines and perspectives can increase its power to improve policy, practice and health outcomes. For example, combining the research that helps us understand climate change, chemical pollution, biodiversity loss and the spread of antibiotic resistance, helps us to re-assess and reshape a more strategic approach to health and care. Evidence and understanding help innovate completely new business, clinical, and partnership models for protecting and improving health. Considering any research or implementation approach in isolation misses the significant advantage of addressing them together. Current mechanisms of assessing health or funding research too often ignore a broad system-wide approach. Interdisciplinary research, implementation and policy needs to work in the following areas:

• Biological and social linkages: Sustainable health and care depends on exploiting the links between the biological and social causes of ill health. This can help drive more personalized healthcare that is tailored to individual needs and focuses on early intervention.
• Use of technology: Technology used by the health system, carers or service users can help shape more sustainable models of care. For instance, people living with bipolar disorder can support themselves with the use of mobile phone technology through earlier and self-identified interactions with professionals.
• Economic factors: Economic mechanisms can help address a more balanced approach to investment over longer time periods, for instance incentivizing outcomes rather than service activity. Historical economic discounting techniques can encourage short term decisions which may be costly to redress in the future. Whole lifecycle assessments also support a more realistic approach by considering costs and impacts from raw products, to manufacture, distribution and disposal.
• Systems: Many interventions that offer long term health and sustainability also add immediate and broader health and social value benefits and help address other major health related issues. For instance ensuring and enabling sustainable food systems also promotes better health at an individual level addressing obesity, diabetes, heart disease and many cancers. The same applies to transport and air quality systems.
• Behavioural/Social: Much health is won or lost outside the formal health care system, hence the importance of collaborative working across the sector, with citizens and community groups. Innovative engagement techniques can help service providers understand the assets, needs and wishes at a local level to help develop more adaptable, flexible and resilient systems and communities.

The following proposals should help support the delivery of sustainable health for all in the decades to come:
o Organizational support: Every organization should have access to sound information on proven innovative technologies and techniques which help reduce the cost and adverse health effects of the system’s environmental impacts. Organizations can use their Sustainable Development Management Plans (SDMPs) or other strategic plans to provide the evidence and data to formulate the business cases for such developments within their organizations and across their local areas.

o Innovative approaches: The development of innovative models of care that consider environmental and social improvements and promote illness prevention, health protection and health improvement needs to be encouraged at all levels. Every organization can align this approach with organizational and strategic plans. Commissioners can develop outcome based commissioning with partner agencies and service users. Regulators can refer to these approaches in their requirements, giving confidence to others, and providers can exploit the multiple environmental, social and financial benefits.

o National group: The health and care system will be supported by regularly convening key research policy, innovation and practice leaders. This national group will help monitor progress, review opportunities and barriers, ensure that key gaps are addressed, implement evidence and stimulate and encourage innovative solutions.

In summary, the following twelve areas of action are proposed to help achieve these measures of success (Sustainable Development Unit, 2015):

• Measuring, monitor and incentivize waste reduction in products and processes;
• Improve cleaner and more efficient energy use;
• Increase the use of less environmentally damaging products;
• Increase the use of data about patient preferences and outcomes to improve sustainable models of care;
• Reduce travel related pollution from the health system;
• Radically decarbonize the energy use of the health and care sector;
• Make more sustainable and flexible use of health service estate;
• Innovate new models of care by embedding sustainability into commissioning;
• Exploit every opportunity to empower service users with technology;
• Exploit every opportunity to empower the system with technology;
• Use innovative low carbon technologies to improve access to timely care; and
• Ensure interdisciplinary research on health and sustainability shapes better policy.

7. Concluding Remarks:
Building a sustainable global response to the demand both for innovations in medical technology and for effective and equitable access to needed technologies is a complex and constantly evolving challenge. While it is often expressed in abstract or political terms, the effort fundamentally concerns how to deliver improved health outcomes. Creating new medical technologies, assessing these technologies, providing for their effective distribution and ensuring that they are used rationally are, ultimately, practical processes. These processes range from the work of laboratory research scientists to the care provided by nurses in a field clinic. However, key measures for success in long-term sustainable public health programs are:
a) Recognized and tested technologies that provide innovative low carbon solutions, helping mitigate the sector’s environmental impacts, are readily identified and organizations are incentivized to adopt them.
b) Gaps in research and barriers to innovation and implementation are addressed systematically and in a multi-disciplinary way to ensure that progress is based on a sound and growing body of evidence.
c) Innovation to reduce environmental impact, enhance social value, reduce cost and improve quality of care is an integral part of the planning, development and delivery of services. It is visible in all elements of the system including the models of care, illness prevention, facilities management, financial mechanisms, and workforce development.

To sum up, one important part of developing a health care system that is fit for the future means using what we already know to shape better policy. It is also important to develop a belief among staff and patients locally that they have the ability to bring about transformational change.

Bibliography and References

1. John Helliwell, Richard Layard and Jeffrey Sachs (2012). World Happiness Report. New York: Sustainable Development Solutions Network.
2. World Organization of the Scout Movement (2016). Goal 3: Ensure healthy lives and promote well-being for all at all ages. Kuala Lumpur: World Organization of the Scout Movement.
3. Karten Taylor (2015). Connected Health: How digital technology is transforming health and social care. London: Deloitte Centre for Health Solutions.
4. Sustainable Development Unit (2015). Module: Innovation, research and technology for a sustainable health and care system. Fulbourn, Cambridge: Sustainable Development Unit.
5. Vincent K. Omachonu and Norman G. Einspruch (2010). Innovation in Healthcare Delivery Systems: A Conceptual Framework. The Public Sector Innovation Journal, Volume 15(1).
6. Preetinder Singh Gill (2013). Technological innovation and its effect on public health in the United States. Journal of Multidisciplinary Healthcare.
7. Mary Whisner (2015). Health & Human Rights Research. Seattle: University of Washington School of Law.
8. World Health Organization, World Intellectual Property Organization and World Trade Organization (2013). Promoting Access to Medical Technologies and Innovation: Intersections between public health, intellectual property and trade. Geneva, Switzerland: World Health Organization, World Intellectual Property Organization and World Trade Organization.
9. David Pencheon and Sonia Roschnik (2015). Saving Carbon, Improving Health. Fulbourn, Cambridge: Sustainable Development Unit.

Richard Laing and Margaret Ewen, Boston University

Name of Lead Authors: Richard Laing and Margaret Ewen
Organizations: Boston University, School of Public Health; Health Action International
Country: USA and the Netherlands

Abstract

This submission argues that the focus of the High Level Panel should be on access to existing essential medicines and that governments need to take action (as listed in Section 2) to ensure medicine availability and to bring prices down. New medicines don’t necessarily equate to better health outcomes; more attention is needed to improve access to those essential medicines that do have proven health impacts.

The authors present evidence that nearly all essential medicines are not patent protected. They identify two TRIPS Plus devices, namely patent linkage and data exclusivity, as potentially serious threats to the entry of generics into a national market once patent protection expires.

By providing summary data from WHO/HAI medicine availability and price surveys, the authors make the case that in low- and middle-income countries’ (LMICs) public sector availability is generally low and patients are forced to seek care in the private sector where prices are high. Availability is worse for chronic NCD medicines compared to medicines for acute conditions. When patients receive care in the public sector they may be obliged to pay high prices as well, with the governments profiting from the sale. High prices often lead to catastrophic health expenditures which can cause families to fall below poverty lines. A frequent reason for these high prices is the failure to use generic medicines.

The authors argue that national governments should promote generic medicines, reduce prices by not charging tariffs and taxes on medicines, remove markups on medicines in government facilities and ensure transparency in medicine pricing. Initiatives such as Zero Mark Up in China, Single Exit Prices in South Africa and the Pharmacia Populares program in Brazil are quoted as examples where governments have taken action to ensure universal access to essential medicines. Such approaches convert the right to health into a practical reality that can be evaluated. 

Submission

While many advocates focus on the affordability of new, extremely high priced, patent-protected medicines, the reality is that existing medicines to treat the global burden of disease often are unavailable in the public sector and are unaffordable in the private sector. Prices of existing essential medicines rarely get attention, particularly from the media. But they matter to millions of patients needing treatment, especially in LMICs, and little is being done to address these concerns. Therefore, this submission focuses on the broad range of obstacles that restrict access to existing medicines and health technologies for people living in LMICs and for poor people living in high-income countries.

Patents are not the primary or most important barrier to accessing these medicines. Many other factors, nearly all of which are under the control of national governments, are far more important in adversely impacting access to essential medicines and technologies. We believe that governments’ fail patients by: applying duties and taxes to medicines; charging excessive markups to patients in public facilities; underfunding medicine purchases which forces patients to seek medicines in the private sector where prices are not controlled; and not promoting generics. The lack of transparency in the medicines supply system leaves patients powerless to confront the situation where many people, including governments, private doctors, pharmacists, wholesalers, distributors and manufacturers profit at their expense. Some LMIC countries, including Brazil and South Africa, have confronted these pressures to some extent.

Patents

In reviews of the WHO Model List of Essential Medicines published since 1991 [i],[ii],[iii] patented medicines have only occupied 5-10% of the items. This reflects the reality that Prescrire[iv] has been documenting for decades that very little true pharmaceutical innovation has been occurring. When innovation with immediate public health impact has occurred, as with antiretrovirals for HIV/AIDS, antivirals for avian influenza and Hepatitis C antivirals, the existing flexibilities within TRIPS and voluntary licensing have worked to ensure access.

Other international regulatory barriers to access: patent linkage and data exclusivity.

While most attention has focused on patents as a barrier to access, there has been far less attention on what the authors believe are far greater threats to access i.e. patent linkage and data exclusivity. Unlike patents, these two barriers are enforced by the national Medicines Regulatory Authority (MRA). These institutions are often understaffed, underfunded and are already challenged to prevent falsified or substandard medicines entering or being produced in the country. Pharmaceutical companies and exporting countries frequently argue for these TRIPS + provisions to be included within bilateral or multilateral trade agreements as patent enforcement, through civil law action, can be slow and depend on companies taking action. By placing the responsibility on national MRAs, companies are likely to gain greater exclusivity and monopoly power to charge exorbitant prices.

Patent linkage occurs when a MRA is required to consider the patent status of a medicine when evaluating an application for market authorization. Conventionally the MRA considers only the quality, safety and efficacy of a product seeking marketing authorization. But some countries, such as the US, require the MRA to consider the patent status when evaluating whether a generic product should be allowed on a national market. MRA staff are unlikely to be competent to assess patent status, and when required to provide this scrutiny less time is available for the vital tasks of ensuring the efficacy, safety and quality of medicines. Some LMICs which joined WTO after the 1995 deadline have been forced to accept such TRIPS Plus requirements and are enforcing completely unnecessary regulations.

Data exclusivity is an even more egregious misuse of trade regulations to create protection for exclusive monopoly marketing. When a patent is granted, the patent owner places in the public domain information about the product and is granted a 20 year exclusive patent protection period. During this time of patent protection, the pharmaceutical company is required to demonstrate to the MRA that the product is of assured quality, is safe to use and is efficacious. Demonstrating efficacy is relatively easy as placebo controlled trials can be undertaken. Such information is submitted to the MRA to receive marketing authorization. With this permission the company has an exclusive right to market their product while they have patent protection. Once the patent has expired, other companies can produce the same medicine and compete once they have received marketing authorization from the MRA. For this they need to demonstrate equivalent quality, safety and efficacy. But to demonstrate efficacy, it would no longer be ethical to undertake a placebo controlled trial as the originator product has already been shown to be more efficacious than a placebo. So the generic company has to undertake a far larger clinical trial to demonstrate that their product is not inferior to the originator product, despite the fact that the efficacy of the now off patent molecule has been proven. Data exclusivity protagonists say such data cannot be used which effectively extends their monopoly and keeps prices high. Many high-income countries do not accept data exclusivity. We urge the High Level Panel to clearly state that data exclusivity should not be used as a barrier to generics entering the market. Patents should determine the period on monopoly market exclusivity not regulatory manipulations.

Availability and price barriers to access in public and private sectors

This section of our submission shows the real access barriers faced by individuals living in LMICs. The vast majority of people in these countries pay out-of-pocket for their medicines[v] and the percentage of people receiving medicines from public sector outlets has fallen between 1995 and 2006. In a series of papers published by Cameron and others the dire situation of people in LMICs has been clearly documented.[vi],[vii],[viii],[ix]

The following figure, published in The Lancet in 20096, shows how availability varies for a core set of essential medicines across 36 LMICs. In the public sector, across all income levels, generic availability averaged about 35% in public facilities.

Figure 1: Average of country-level mean percentage availability of medicines, by World Bank income group. Data are mean (maximum/minimum).

In the private sector, generic availability was about 65% and the availability of originator products increased as the wealth of the countries increased. In 2011, Cameron and others in a  WHO Bulletin7 article showed that acute medicines were far more available than chronic medicines in both the public and private sectors (see table below). So what does a patient in a LMIC do when they need treatment for a chronic NCD?

They are likely to firstly go to the public health facility in the hope that the product is available and affordable. As shown in The Lancet 2009 article, governments usually procure at prices close to the international reference price with some notable outliers. But if the medicine is not provided free-of-charge, the patient will be paying from 3 to 11 times the reference price in the public sector. In the private sector, the patient would pay from 8 to 21 times the reference price for the lowest price generic medicine and far more for originator products. The reasons for high prices of medicines, particularly in the private sector in LMICs, is due to a combination of government actions and inactions and the willingness by the private sector to maximize returns without considering the needs of patients.

Price and affordability

While it may appear intuitive that the price paid for a medicine directly relates to affordability and poverty, it is difficult to demonstrate a direct relationship. Based on prices found in outlets, the WHO/HAI survey method expresses affordability as the number of days’ wages needed by the lowest paid unskilled government worker to buy a standard course of therapy and uses one days’ wages as the cut off for affordability. While this is easy to understand, one Indian survey manager pointed out that 72% of individuals in her state earned less than the lowest paid government worker. Laurens Niens et al9 used two other measurements of affordability, impoverishment and catastrophic expenditure, and showed that for many poor people in Indonesia and elsewhere buying medicines frequently pushed them below poverty levels. A key finding of this groups work was that purchasing originator products, rather than generics, would have a dramatic negative effect on the level of poverty.[i] They quote a finding from the Philippines where purchasing originator brand atenolol (for hypertension) would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift would only be 7%.

Promoting generic medicines

In the World Health Report 2010, WHO identified the promotion of generic medicines as a key action that could be taken to improve access by making medicines more affordable. They quoted a recent study of 18 medicines in 17 largely middle-income countries that revealed costs to patients could be reduced by an average of 60% by switching from originator brands to lowest priced generic equivalents.[ii],[iii] Some countries, such as the US, have very high rates of generic uptake (86%) but many other high, middle- and low-income countries have very low rates of generic medicine usage. There are many reasons for this finding but concern about quality is an often quoted issue. However, even in countries such as Austria where medicine quality is assured to EU standards, generic use may be very low due to government inaction. In the US and some other countries, actions are taken to speed the entry of generics into the market when the patent expires, and generic substitution is compulsory.

Government’s involvement in the relatively high price of essential medicines in LMICs

Governments frequently apply duties and taxes on medicines.[iv],[v] This is clearly bad public policy. Governments impose taxes for two purposes; firstly to generate revenue and secondly to achieve social purposes. Thus taxing alcohol or cigarettes aims to reduce harmful health effects. Charging an income tax aims to reduce income inequality, but charging a tax on medicines is clearly regressive as the sick are likely to be poor, elderly and suffering from an illness that may prevent them earning. As mentioned above, governments frequently procure efficiently and then sell to their people at considerable profits. As part of national health reform China introduced a policy of Zero Mark Up in public health institutions to prevent this abuse.[vi]

Governments shirk their responsibilities to protect consumers in other ways, including providing information, to both consumers and health care providers, about the equivalence of generic and originator medicines. The Lancet 2009 article showed that using generics, rather than high priced originator brands, would shave about two thirds off the price and hence improve affordability. Monitoring and controlling medicine prices can protect the consumer. This has been successfully done in South Africa with a Single Exit Price with the banning of discounts and rebates for “good” customers.[vii] Brazil has established Pharmacia Populares which provide a limited basket of mainly NCD medicines for patients who register for access to these schemes through the public and private sector facilities.[viii] The provincial administration in the Western Cape province of South Africa have established a Chronic Diseases Unit which centrally pack and distribute each month individually packed chronic disease medicines for nearly 300,000 patients in more than 216 distribution or dispensing points. This is done with a very low stock out rate and at an affordable cost to the province and no cost to the patient.[ix]

Conclusion

This submission aims to persuade the High Level Panel on Access to Medicines to focus on access rather than innovation. While it may appear that having new medicines available would improve public health, the empirical evidence is that this is generally not the case. We have many good medicines that could effectively treat the vast majority of illnesses but these medicines are not universally accessible. Either they are not available or are priced at a level that makes them unaffordable. The global pharmaceutical market is estimated by IMS Health to be worth $1.4 trillion dollars in 2020. Many people and companies in both high- and lower-income countries profit from these sales. Patients need the protection of their governments against being exploited especially when they lack the necessary information to make informed choices. Governments have obligations to their citizens to ensure that safe, effective medicines are universally available at a cost that will not impoverish the patient or their family when they need treatment. The Right to Health is a meaningless slogan if it does not include guaranteed access to effective essential medicines. If the level of universal access to essential medicines is used as a measure of how well a country ensures the right to health, this right will become measurable in a stable comparable way so progress to achieving it can be tracked.

Bibliography and References

[1] Howard, N.J., Laing, R.O., "Changes in the World Health Organization Essential Drug List," The Lancet, Vol. 338, pp. 743-745, Sept. 21, 1991

[2]Laing R, t’Hoen E, Waning B, Ford N Twenty Five years of the WHO Essential Medicines List Lancet 361 1723-1729 2003

[3] The World Medicines Situation 2011 - Selection of Essential Medicines available at http://apps.who.int/medicinedocs/en/m/abstract/Js18770en/

[4] Prescrire available in English at http://english.prescrire.org/

[5] The World Medicines Situation 2011 - Medicine Expenditures
(2011) available at http://apps.who.int/medicinedocs/en/m/abstract/Js18767en/ See Figure 1.9 page 15

[6]Cameron A, Ewen M, Ross.Degnan D, Ball D, Laing R Medicine Prices, availability and affordability in 36 developing and middle income countries: a secondary analysis Lancet published on line December 1, 2008 DOI+10.1016/S1040-6736(08)61762-6 Print version Lancet. 2009 Jan 17;9659:240-249 available at http://apps.who.int/medicinedocs/documents/s17061e/s17061e.pdf

[7] Cameron A, Roubos I, Ewen M, Mantel-Teeuwisse AK, Leufkens HGM & Laing RO,  Differences in the availability of medicines for chronic and acute conditions in the public and private sectors of developing countries Bulletin of the World Health Organization 2011; 89:412-421. doi: 10.2471/BLT.10.084327 available at http://apps.who.int/medicinedocs/documents/s18066en/s18066en.pdf

[8] van Mourik MSM, Cameron A, Ewen M and Laing RO Availability, price and affordability of cardiovascular medicines: A comparison across 36 countries using WHO/HAI dataBMC Cardiovascular Disorders 2010, 10:25doi:10.1186/1471-2261-10-25

[9] Niëns LM, Cameron A, Van de Poel E, Ewen M, Brouwer WBF, Laing RO. (2010) Quantifying the Impoverishing Effects of Purchasing Medicines: A Cross-Country Comparison of the Affordability of Medicines in the Developing World. PLoS Med 7(8): e1000333. doi:10.1371/journal.pmed.1000333

[10] Niëns, L. M., Cameron, A., Van de Poel, E., Ewen, M., Brouwer, W. B., & Laing, R. (2010). Quantifying the impoverishing effects of purchasing medicines: a cross-country comparison of the affordability of medicines in the developing world. PLoS Med, 7(8), e1000333. Available at http://apps.who.int/medicinedocs/documents/s17402e/s17402e.pdf

[11] WHO World Health report 2010 Chapter 4 Available at http://www.who.int/whr/2010/10_chap04_en.pdf?ua=1

[12] Cameron, A., Mantel-Teeuwisse, A. K., Leufkens, H. G., & Laing, R. O. (2012). Switching from originator brand medicines to generic equivalents in selected developing countries: how much could be saved?. Value in Health, 15(5), 664-673.Available at http://apps.who.int/medicinedocs/documents/s19556en/s19556en.pdf

[13] Olcay M and Laing R. Pharmaceutical Tariffs: What is their effect on prices, protection of local industry and revenue generation? 2005. Available: http://www.who.int/intellectualproperty/studies/tariffs/en/index.html

[14] Sales taxes on medicines by Andrew Creese (2011) WHO/HAI Review Series on Pharmaceutical Pricing Policies and Interventions. Working paper 5: available at http://www.haiweb.org/medicineprices/05062011/Taxes%20final%20May2011.pdf

[15] Mao Wenhui, Chen Wen (2015) The Zero Mark-up Policy for essential medicines at primary level facilities  China case study WHO reference number: WHO/HIS/HGF/CaseStudy/15.2 WHO Available at http://www.who.int/health_financing/documents/Efficiency_health_systems_China/en/

[16] South Africa Medicine Price Registry Available at http://www.mpr.gov.za/

[17] Bertoldi, A. D., Helfer, A. P., Camargo, A. L., Tavares, N. U., & Kanavos, P. (2012). Is the Brazilian pharmaceutical policy ensuring population access to essential medicines?. Globalization and health, 8(1), 1.

[18] Magadzire, B. P., Marchal, B., & Ward, K. (2015). Improving access to medicines through centralised dispensing in the public sector: a case study of the Chronic Dispensing Unit in the Western Cape Province, South Africa. BMC health services research, 15(1), 1.Available at http://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-015-1164-x

Thomas Pogge, Incentives for Global Health - Yale University

Submission From: Incentives for Global Health, Yale University
Prepared by: Thomas Pogge
Country: USA

Abstract

We propose the Health Impact Fund (HIF) as a new way to incentivize and pay for pharmaceutical innovation. The HIF is meant to address the inherent deficiencies of the existing patent monopoly system for pharmaceuticals by providing a complementary, pay-for-performance mechanism. By more closely aligning the economic incentives for innovators with global public health needs, the HIF aims to draw to market badly needed health technologies that are not sufficiently profitable under TRIPS. Pharmaceutical innovators worldwide would have the option of registering new medicines with the HIF. By registering, an innovator would agree to provide its drug at or below cost anywhere it is needed and, in exchange for foregoing normal sales profits, would be rewarded based on the HIF’s assessment of the drug’s health impact. The HIF would have a fixed pool of money to pay out annually. Every year, any HIF-registered product would receive a share of the pool equal to its share of the health impact achieved by all registered products. The HIF would be an international fund, financed by willing governments according to national income. The costs to governments and taxpayers would be largely offset by lower prices on drug purchases and insurance premiums.

The HIF model has been refined over ten years, incorporating important contributions from prominent members of government, industry and civil society. It is now ready to be tested experimentally. Owing to the financial and technical ambition of the HIF, we propose a smaller pilot (the “miniHIF”) to demonstrate feasibility as well as to illuminate potential challenges. The miniHIF would be a time-limited competition among several pharmaceutical innovators willing to register new health technologies, with rewards allocated on the basis of measured health impact.

Submission

The Health Impact Fund (HIF)
The proposed Health Impact Fund would be a permanent mechanism to support biopharmaceutical innovation. By registering a new product with the HIF with the commitment to make it widely available at cost, any pharmaceutical innovator would become entitled to participate in HIF reward payments. Funded mainly by willing governments, the HIF would distribute fixed annual reward pools. Each annual pool would be divided according among the registered products according to the health gains each product had achieved in the relevant year, with products eligible to receive payments for ten years.

The HIF is designed to address three critical failings in our current system.

First, it would help address the significant gap in incentives for innovation in pharmaceuticals. In particular, the HIF would create effective rewards for innovators that invest in therapeutically important innovations that are commercially unattractive in our current system. For example, diseases concentrated among the poor, for which the commercial returns are too small to justify investment in needed therapies, could become attractive targets given the existence of the HIF.

Second, the price of HIF-registered drugs would be capped at the cost of manufacture and distribution. Registered medicines would therefore have much greater reach, especially among poorer patients, than has been typical for high-priced modern drugs.

Third, the HIF is designed so that the registrant has an incentive to ensure that the product is available. Many schemes that rely on low prices alone to enable wide distribution do not create a commercial incentive to extend availability to poor people in remote areas, since there is no profit in selling low-margin products to them. The HIF, by making rewards dependent on health impact, will make it profitable for innovators to invest in reaching poor, rural patients. These incentives would stimulate innovators to make greater efforts to collaborate with local health authorities and clinics, and to increase investment in distribution.

Collectively, these changes to the way important drugs are developed, priced, and distributed would have substantial impacts on public health.

*Technical feasibility*
The key technical challenge for the HIF is to develop a system of health impact measurement. Such a system needs to be cost-effective, credible, and, as much as possible, consistent across diseases and countries. While the specific assessment plans to be worked into the various registration contracts must take account of each medicine’s specific characteristics, such variations must be grounded in a coherent overall framework for the fair and efficient assessment of health gains.

Although the idea of basing rewards on health impact sounds ambitious, the HIF would operate much like many national insurance systems, such as the UK’s NHS. In the NHS, reimbursed prices are typically related to expected health impact, where the analysis of health impact is based on clinical trial data. The HIF could do the same: estimate health impact on the basis of pre-approval clinical trials. Of course, it would be attractive to improve on this to the extent that it was feasible and cost-effective to collect additional post-marketing information. There has been a substantial growth in pay-for-performance pricing schemes in recent years, with many products, for example, offering money-back guarantees if the patient does not respond (Garrison 2013).

Many countries do not have the administrative structures in place to facilitate data collection. We therefore anticipate that the HIF may spend up to 10% of its total budget on the assessment process. While costly, the assessments would yield much data with independent clinical value, data that could be shared with local health authorities to improve the delivery of health care. We also anticipate that the incentive associated with registration would encourage innovators wishing to register drugs with the HIF to design clinical trials that enable clearer assessment of the incremental health impact of the drugs. The same incentive would encourage innovators to collect information demonstrating product effectiveness, further supplementing the data available to the HIF.

The miniHIF discussed below would serve as an excellent test of the technical feasibility of the HIF.

*Financial feasibility*
*Funding*
We have estimated that the optimal minimum efficient scale for the HIF is roughly $6bn per year – enough to sustain meaningful rewards for approximately 20 new drugs at a time. The HIF would therefore depend on substantial annual funding from governments/taxpayers. However, the HIF would also create commensurate savings through lower prices for registered products, since all products must be sold at a low price during the reward period. That is, although the proposed annual rewards sound imposing, the net cost to taxpayers would be much less and could even be negative. The main effect of the HIF is to reorganize the way we pay for some medicines, rather than to increase the amount of funding for them. Since current global pharmaceutical expenditures are approaching $1 trillion, the proposed scale of the HIF would represent a small fraction of the market.

*Cost-effectiveness*
The HIF can be seen as the logical extension of the move towards value-based pricing by national drug insurers. There are a number of ways in which the HIF is particularly well suited to delivering a cost-effective solution.

First, the HIF is designed so that it pays only for success. There are no payments if a product is not ultimately developed; no payment if a product is developed but not appropriately used; and no payment if a product is developed, delivered, appropriately used but no better than the therapy it replaces.

Second, the HIF is designed so that registered drugs are cost-effective. Any drug that can generate more profits outside the HIF will not be registered. But that means that the cost to payers per unit of health impact must be lower for products registered in the HIF. In other words, registered products will have a lower cost-benefit ratio than those that are not registered.

Third, the HIF is cost-effective in that it creates competition among drugs of different therapeutic classes for the same stream of rewards. This means that payers don’t spend too much in one area while starving others because of political decisions about trying to target “fashionable”diseases rather than those that can most effectively be addressed.

Fourth, the HIF is cost-effective in that it doesn’t constrain the ways that innovators can generate health benefits. Not only are there no constraints on therapeutic class, there are no artificial constraints on the (legal) activities innovators can engage in. For example, an innovator might earn profits by focusing on developing a better product; or it might earn profits by investing more heavily in distribution or in price-cutting to increase sales to marginal populations. The HIF doesn’t favor any one of these activities over any other. Instead, it enables innovators to do whatever will most cost-effectively deliver health impact through new pharmaceuticals.

Finally, the HIF is cost-effective because it would create incentives to invest exactly in the areas that are most underserved. The least appealing investments, today, of course, are those for which potential payers are poor and unable to pay high prices. The HIF would therefore target exactly those investments with the best mix of likely health gains and smallest profitability under the current system.

*Intellectual property management issues*
The HIF is designed to complement existing intellectual property systems. It leaves unaltered the patent system and addresses any deficiencies by creating an alternative payment system

One of the key HIF design issues is to specify the contractual requirement that will ensure that registered drugs are available at low prices. Possible models include open licensing of registered drugs, as in the Medicines Patent Pool; tendering production by a small number of generic manufacturers; or price regulation based on estimated cost (Hollis 2009). The optimal design will likely depend on the individual drug, given variation in the competitiveness of manufacturers in different drug markets and the distribution systems. In all cases the innovator would retain IP, but would be required to give up certain rights in exchange for HIF rewards. In all cases, at the end of the reward period, the innovator would be required to offer open licenses for production of the registered product.

*De-linking*
The HIF is a “de-linking” proposal since it separates the reward for innovation from the price (Love and Hubbard 2007). This kind of approach has several benefits. First, it enables low prices for registered products, to enhance access. Second, it improves incentives for innovation for products having high therapeutic value, but poor commercial prospects. Third, it increases the incentives for innovators to supply products even when prices are low, thus increasing availability.

*Equity*
Two key principles of the HIF relate to equity and distribution. The first is that all human lives should be valued equally, regardless of ability to pay or other factors. The second is that the distribution of the cost of innovation among countries should be progressive, and thus based on income rather than need.


*Accountability*
The HIF must generate reliable and high quality health impact data in order to fairly allocate rewards among registered medicines. Innovators will be competing to obtain rewards, and this competition for fixed annual pools ensures that the HIF has to be responsive and will be accountable to the registrants for having a fair process. At the same time, governments that are funding the HIF will be interested in knowing that their contributions are being used appropriately. Therefore, the HIF must be explicitly accountable both to governments and to participating innovators, and have their confidence in executing its role in a fair and independent manner

Preliminary proposals for governance of the HIF are described in Chapter 4 of Hollis and Pogge (2008). The board would likely be composed of contributing countries, representatives of agencies with a public health interest such as the WHO, and representatives of NGOs and patient groups. The internal organization could consist of a technical branch, which would establish general rules for assessing health impact; an assessment branch, which would apply those rules to determine the health impact of individual products; an audit branch; and support branches for finance, IT, and human resources.

*Synergy with Product-Development Partnerships (PDPs)*
The HIF is structured to work with other mechanisms such as PDPs and open source science. The HIF offers three key benefits to PDPs. First, if the PDP were structured so that the product is required to be registered with the HIF, then there would be a mechanism to control price. Second, despite the pricing limitations, there would be commercial incentives to increase availability of the product in developing countries. Third, the HIF would create a funding system for successful PDPs: they could presumably share rewards with the commercial partner, and these rewards would in turn provide ongoing funding to the public partner. See Hollis and Pogge (2010).

*********
*Piloting the HIF: miniHIF*
A frequent comment on the HIF is that it is an ambitious project that needs to be tested out at a smaller scale. There are already many tests of pay-for-performance mechanisms being used in pharmaceutical markets. However, it would be helpful to see a competitive pay-for-performance arrangement mainly in low- and middle-income countries. We therefore propose the “miniHIF”.

The miniHIF would be a competition for pharmaceutical firms and PDPs to achieve health impact through an innovative drug, vaccine, delivery mechanism or formulation used mainly in low- and middle-income countries (a “project”). Pharmaceutical innovators would be invited to bid through a Request for Proposals; successful proposals would become eligible for rewards based on health impact achieved through the initiative. Proposals would be screened on the basis of expected health impact; a commitment to extending access to poorer populations; and measurability.

The available reward pool would be divided among the accepted projects in proportion to the health impact achieved by each during a defined period of time (e.g. 3 years). The miniHIF could be structured to operate within an existing institution, in the same way, for example that the AMFm was managed by the Global Fund.

We propose the miniHIF to be funded in the range of $60m - $200m; a larger amount would allow more proposals to be funded, and would draw in more ambitious proposals. The amount must be sufficient to pay for the administration of the competition, as well as the assessment of health impact. The Institute for Health Metrics and Evaluation has agreed in principle to perform the assessment function for the miniHIF. The average amount awarded per proposal should be enough to attract serious proposals, i.e. at least $25m.

Starting from the miniHIF, it would be possible to increase the scale of pilots, ultimately concluding in a fully competitive, permanent HIF.

For more details on the miniHIF, please see http://healthimpactfund.org/wp-content/uploads/2016/02/mini-HIF-proposal-2016-Feb.pdf


*Evidence*
1. A key piece of evidence in favor of the HIF approach is the explosive growth in cost-effectiveness and comparative-effectiveness studies and the use of such data by national insurers. While the HIF would not engage in cost-effectiveness analysis, it would engage in effectiveness analysis. More recently there is an increasing use of performance-based reimbursement agreements between pharmaceutical manufacturers and insurers. The rapid growth in this approach indicates that it is a useful tool and that it has validity in practice.
2. A second key piece of evidence is that there are gaps in the set of innovative drugs that are commercially attractive. While PDPs are effectively addressing some of those needs, areas of need remain. (See, Moran et al 2011, p. 85.) The HIF would rely on the ingenuity of pharmaceutical innovators to identify and take full advantage of the most compelling opportunities for realizing cost-effective health gains.
3. Price remains an important barrier to access to drugs, even given price discrimination and donation programs. (See, e.g. Chauduri et al 2003 and Saul 2008 for examples in very different settings). Part of the problem is high retail mark-ups that are not effectively controlled by suppliers. (See, e.g. WHO 2008).
4. Even aside from issues of price, availability is sometimes an important barrier when there are inadequate commercial incentives to ensure effective supply (See, WHO 2006, p. 99). Barriers to availability may include inadequate diagnostic resources (including health care personnel) and incomplete distribution systems. (See, e.g. Kotwani 2007). An appropriately motivated supplier could contribute to overcoming these barriers to availability.

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Summary

*Impact on policy coherence: The HIF offers a mechanism that recognizes (1) the central role of the pharmaceutical industry in developing and bringing new medicines to market within our existing system of intellectual property; (2) the importance of price as a condition for access; and (3) the importance of incentives for improving human health through medicines. The HIF would reward pharmaceutical innovators according to how well they serve public health goals.

*Impact on public health: The HIF, by design, would create incentives to expand the set of medicines, by creating commercial incentives where none now exist and spurring need-based pharmaceutical innovations. In addition, by delinking price from the reward for innovation, the HIF would enable wider access of essential drugs to those in need.

*Advancing human rights: The fundamental feature of the HIF is that all lives are valued equally, regardless of ability to pay. As such, the HIF offers a practical way of realizing the human right to health.

*Implementation: The HIF is an ambitious proposal. The miniHIF offers a path to test the feasibility and effectiveness of this system of competitive rewards based on actual health impact. It would also offer a starting point for countries to work together to fund this first-of-its-kind project.


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Expressions of Support

***Janssen Pharmaceuticals (letter, Aug 12 2015)

“The purpose of this letter is to express the support of Janssen, the Pharmaceutical
Companies of Johnson & Johnson, for the proposed Health Impact Fund and miniHIF. …

“With sufficient funding, the HIF could be an effective way of stimulating investment from small and large bio-pharmaceutical companies to address the needs of low-income populations. It would align commercial incentives with social goals of reducing excess morbidity and mortality. It could support companies, including Janssen, in their efforts to develop innovative products within a competitive, market-based framework that rewards outcomes.

“It would be sensible to test the viability of the HIF approach at a smaller scale. A timelimited ‘miniHIF’ could demonstrate the responsiveness of firms to competitive
performance-based rewards, and could provide a live example of measuring performance in challenging environments.
…
“We hope to see the miniHIF funded, and would certainly make an effort to participate. We will also be pleased to provide our views on the structure and design details of the miniHIF and to help propagate the project among our peers within industry associations and beyond.”


***German Social Democratic Party, Motion (16 June 2010)
“The German Bundestag calls on the Federal Government … to actively support the pilot phase of the HIF under the auspices of the Global Fund, and to financially and actively support and promote the establishment of a HIF, tested through evidenced efficacy.”

Renewed with Bilateral Support in the Bundestag, 19 May 2015

***Liberal (Venstre) Party of Norway (June 2015)
An international Health Impact Fund (HIF) should be established as a supplement to the current patent system. Through HIF pharmaceutical companies can voluntarily register their drugs and commit to making them available at the lowest price against payment of support over ten years from the Fund on the basis of major health impact their drugs have. This gives companies incentives to develop medicines for those with the greatest health needs and not only those with the greatest purchasing power.

Bibliography and References

References
Chaudhuri S, Goldberg P, Jia P, 2003. Estimating the Effects of Global Patent Protection in Pharmaceuticals: A Case Study of Quinolones in India. NBER Working Paper No. W10159, December.
Garrison, Louis P., Adrian Towse, Andrew Briggs, Gerard de Pouvourville, Jens Grueger, Penny E. Mohr, JL Hans Severens, Paolo Siviero, and Miguel Sleeper. "Performance-based risk-sharing arrangements—good practices for design, implementation, and evaluation: report of the ISPOR good practices for performance-based risk-sharing arrangements task force." Value in Health 16, no. 5 (2013): 703-719.
Hollis A, 2009. The Health Impact Fund and Price Determination. Incentives for Global Health Discussion Paper #1, available at http://healthimpactfund.org/wp-content/uploads/2015/12/DP1_Hollis.pdf
Hollis A, Pogge T, 2010. Product-Development Partnerships and the Health Impact Fund. Incentives for Global Health Discussion Paper #9, available at http://healthimpactfund.org/wp-content/uploads/2015/12/DP9_Hollis-Pogge_PDPs.pdf
Kotwani A et al, 2007. Prices & availability of common medicines at six sites in India using a standard methodology. Indian Journal of Medical Research 125: 645-654.
Love, James, and Tim Hubbard. "The Big Idea: Prizes to Stimulate R&D for New Medicines." Chicago-Kent Law Review 82 (2007): 1519.
Moran M et al, 2011. Neglected disease research and development: Is the global financial crisis changing R&D? Policy Cures G-Finder report for 2010.
Saul S, 2008. In Sour Economy, Some Scale Back on Medications. New York Times, October 21: A1.
WHO, 2006. Report of the Commission on Intellectual Property Rights, Innovation and Public Health. WHO, 2008. "Medicine Prices in Kenya" available http://www.who.int/medicines/areas/technical_cooperation/MedicinepricesKenya.pdf


A Bibliography of the HIF
For more on the HIF generally, see
Hollis A, Pogge T, 2008. The Health Impact Fund: Making New Medicines Accessible for All. Incentives for Global Health.

Extensive materials on the HIF are available at the HIF website: www.healthimpactfund.org
For a short summary of the HIF proposal, see
Banerjee A, Hollis A, Pogge T, 2010. The health impact fund. Lancet. 375(9727):1693

For a discussion of how the HIF might be used to assist in the development of antibiotics, see
Outterson K, Pogge T, Hollis A, 2011. Combating antibiotic resistance through the Health Impact Fund. In Glenn Cohen, ed. The Globalization of Healthcare. Oxford University Press 2012.

For a discussion of the ethical foundations of the HIF approach, see
Pogge T, 2009. The Health Impact Fund and Its Justification by Appeal to Human Rights. Journal of Social Philosophy 40, no. 4, 542–569.

For independent analyses of the HIF, see
Amisano F, Cassone A, 2011. Economic sustainability of an alternative form of incentives to pharmaceutical innovation. POLIS Working Papers n. 181.
Grootendorst P, 2009. How Should We Support Pharmaceutical Innovation? Expert. Rev. Pharmacoeconomics Outcomes Res. 9(4): 313-320.
Lexchin J, 2010. One step forward, one step sideways? Expanding research capacity for neglected diseases. BMC International Health and Human Rights 10:20.
Longo, CJ, 2011. Encouraging pharmaceutical innovation to meet the needs of both developed and developing countries. International Journal of Development Issues, 10(1): 92-101.
Pekarsky B, 2010. Should Financial Incentives be Used to Differentially Reward ‘Me-Too’ and Innovative Drugs? Pharmacoeconomics 28(1): 1-17.
Rubio JC, 2015. Ebola, R&D on Neglected Diseases and the Health Impact Fund. http://ssrn.com/abstract=2663616.
Timmermann C. 2012. "The Health Impact Fund and the right to participate in the advancement of science." European journal of applied ethics 1, no. 1 (2012).

Chandni Raina, Centre for WTO Studies, Indian Institute of Foreign Trade_A

Submission From: The Centre for WTO Studies, Indian Institute of Foreign Trade
Prepared by: Chandni Raina
Country: India

Abstract

Access to medicines has become a critical issue with most developing countries being pressurized to move far beyond TRIPS- whether it is as part of their compliance with the WTO Agreement or as part of the bilateral FTAs / RTAs being entered into with developed countries. Important policy space provided by TRIPS such as the ability to define patentability criteria, interpretation of Article 39.3 on undisclosed information submitted to the regulator, circumstance that would call for issue of compulsory license are sought to be progressively reduced or controlled. In this scenario, it is important to import the concept of ‘standard essential patents’ used in the telecom sector and also in environment technologies (in some countries) to allow for mandatory licensing as long as the treatment protocol includes that patented drug.

Submission

Submission by Centre for WTO Studies, Indian Institute of Foreign Trade to the UN Secretary General’s High Level Panel on Access to Medicine

A. Rationale of the Submission

Most patented medicines are priced out of reach of the patients in developing countries and LDCs . Sofosbuvir for treatment of Hepatitis C priced at US$84000 in the US market for a three month treatment and the case of Nexavor, a renal cancer drug, priced at Rs. 280,000 for a month’s treatment in India are a case in point. Predatory pricing of patented drugs and the resultant impact on access is also well documented in the decision of the Indian Controller General of Patents, Designs and Trademarks in the Natco Pharma Ltd Vs Bayer Corporation (Nexavar) . The fact that at that price Bayer could only meet 2% of the total demand for that medicine in the country indicates complete policy incoherence between protection of IP, promoting access to public health and trade. It also buttresses the view that developing countries and the LDC are not the relevant market for the patented medicines. While safeguards in the TRIPS Agreement such as the issue of compulsory license exist, it has become increasingly difficult to take recourse to it. The extent of concern among the developed countries on the issue of a single compulsory license by India or the cases of compulsory license granted in Thailand makes it quite clear that the probability of use of the measure is likely to be very low. This makes it an unviable option if access to medicine has to be addressed in a substantive and comprehensive manner. The measure also creates inherent uncertainties and is liable to be challenged making it difficult for generic producers to use this option. We should therefore institutionalize the concept of standard essential patents in the same manner as it is done in the telecom sector to address a more important public need.

B. Model to Address this Policy Incoherence

The model developed is based on the concept of “standard essential patents” used in the telecom sector with a few modifications to address the distinctiveness of pharma over telecom. In fact a 'standard essential patent' type of model has also been applied in making environment technologies accessible in the US. The Environment Protection Agency (EPA) in the US can apply to the Attorney General for a mandatory license for a patent covering a technology necessary to enable compliance with the hazardous air pollutants standards, or motor vehicle emission standards of the Clean Air Act. Under section 308 of the Clean Air Act, the United States may require the owner of the patented technology to grant the non-complying party a patent license in exchange for a reasonable royalty if the patented technology is necessary to meet the requirements in certain sections of the Clean Air Act. Treatment of most diseases has a clear protocol- whether it concerns prevention through vaccines or treatment after onset of the disease. This is true for lifestyle diseases such as diabetes, hypertension, mental illnesses and cancer and also in respect of HIV or communicable diseases such as Tuberculosis, Malaria, or other vector borne diseases. The proposal is that once a protocol of treatment is decided upon, all patents that are set down as critical for the treatment of the disease should be called “standard essential patents”. Such patents that are critical to implement the protocol should then be available to be manufactured by a pharmaceutical company that is prequalified by WHO to do so (after due application) on payment of reasonable and non discriminatory (RAND) royalty. The royalty to be paid could be decided by the concerned companies i.e. the originator and the applicant on mutual consent or could be fixed in case of a dispute by a judicial authority. Country jurisdictions would have the freedom to decide whether interim injunctions could be applied in such cases. It may be highlighted that interim injunction seriously compromises the possibility of negotiating on RAND terms and is therefore best avoided. Besides, given the impact medicines have on public health it is advisable that other means such as directing the alleged infringer to maintain all the transactions related to the medicine in a separate bank account could be considered.

C. Mechanism of Implementation

The mechanism of implementation could be as follows: Step 1: WHO sets up an expert group involving medical specialists, innovator and generic companies, concerned experts and representative group of member States to set down the protocol for treatment of major diseases whether lifestyle related or vector borne. WHO has considerable experience in this area. Given the vast public safety and health angle of the impact it is important that the exercise be conducted under the aegis of this body unlike SEPs in the context of telecom where it is primarily the research based companies that have come together. Moreover involvement of generic companies is essential because these organizations have considerable expertise in developing improved versions of the drug such as pediatric dosage, fixed dose combinations etc which in turn may further refine and improve the treatment protocol. This group could deliberate upon the new proprietary technologies and the appropriate stages when these could be applied in the treatment of a disease. The committee could also discuss problems, if any, in the treatment and deliberate upon future treatment course or options. Step 2: The patents that get included in the treatment protocol would be called the standard essential patents. These technologies could be used by any company other than the originator on payment of royalty on RAND terms in markets where the product is already patented. It is understood that in territories where the drug is not patented, the generic manufacturers would be free to manufacture the product without requiring to pay any royalty. Further improvements such as fixed dose combinations, paediatric dosage forms, and sustained release molecules of the same product when developed by a company could be used by another on payment of royalty, if there is a patent on that form in the country in which it is proposed to be marketed. Step 3: While royalties could be determined by the two parties to the deal, guidelines could also be drawn up by the WHO which would guide the process of fixation. Disputes if any will be resolved as per judicial decisions in the country where the generic company is incorporated or where the product is to be licensed. Interim injunctions could be avoided given the impact they are likely to have on public health matters. Who may also be required to come out with a statement on the undesirability of interim injunctions in case of medicines.

D. Manner in which the Suggestion impacts Innovation, Public health, Human Rights and Trade

i) Impact on Innovation a. The discussions in the ‘expert body’ comprising of originator companies, generic producers and medical experts could bring in greater synergy in developing improved drugs for treatment of specific diseases. The telecom standards body such as the International Telecom Union and European Telecom Standard Institute have helped in development of new standards in the telecom arena and one may not be amiss in reckoning a similar impact on treatment protocol for diseases. b. Involvement of Generic producers could help in pushing them into R&D through collaborations and cooperation. In any case licensing on non exclusive basis will unleash competition which in turn will promote innovation in product delivery, improvements in the drug such as fixed dose combinations and extension to new patient groups through paediatric dosage and better compliance with sustained release forms of the molecules. c. Payment of royalty, expansion of the markets for medicines due to competition and reduced prices will generate revenue for the innovator companies. This will not only extend their reach but also allow them to utilize the distribution network of the generic companies to their advantage. d. Transfer and dissemination of technology will impact social and economic welfare and facilitate the realization of Article 7 (Objective) and Article 8 (Principles) of the TRIPS Agreement. e. Despite the average success rate of three in 10 drugs , the extent of expenditure incurred by innovator pharma companies in R&D is not without reservation. Many question the extent of expenses incurred by these companies in marketing as against Research and Development. Moreover, research also shows that that public sector research institutes have had an extensive role in the discovery of drugs and vaccines especially in medicines that are expected to have disproportionately higher clinical effect. This is also corroborated with findings that public sector has both direct and indirect impact on overall research. Innovation by Pharma companies may therefore not be adversely affected. In fact the synergies achieved and the expansion in the market due to non exclusive license may have an overall beneficent impact. ii) Impact on Access to Medicine and Public Health a. One of the crucial reasons for the inability of people and countries to get medicines is its price. Technology transfer in a non exclusive basis will bring in competition and help to reduce the prices of medicines. Better distribution networks of the generic companies coupled with lower prices will also extend the reach to new markets. The role generic companies have played in enabling access to HIV Medicines in the world is evidence that this model can indeed work. b. With lower prices, the mechanism will also reinforce the work of various aid giving humanitarian organizations which procure life saving drugs by enabling them to extend their services to more people and countries. c. More significantly the model being proposed will have a profound impact on prices and access because under this, license would be given for manufacture of the medicine with no territorial restriction on its application-as long as a country is a middle income or a low income country. The economies of scale and the competition unleashed will be precursors to reduced prices, improved products and improved access. iii) Impact on Human Rights The model seeks to enhance competition, create economies of scale and incentivize innovation by generic companies while compensating innovative efforts of the originator companies through payment of royalty. The measure will improve availability and affordability of life saving drugs in low income and middle income countries. It would therefore impact the Sustainable Development Goal No. 3 on promoting health for all positively. The proposal will directly impact two targets set to be achieved by 2030 - ie- a.To end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases b.To reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being while also impacting the others indirectly. iv) Impact on Trade According to the WHO, “although trade in medicines is increasing rapidly, most of it takes place between wealthy countries, with developing countries accounting for just 17% of imports and 6% of exports. It is estimated that one-third of the developing world's people are unable to receive or purchase essential medicines on a regular basis.” The measure being suggested will address this and promote trade in medicine among the Developing and the Least Developed Countries by removing the barriers to technology transfer and dissemination.

Bibliography and References

1. Ellen F. M. ’t Hoen “TRIPS, Pharmaceutical Patents and Access to Essential Medicines: Seattle, Doha and Beyond”
2. Natco Pharma Limited v. Bayer Corporation, Compulsory License Application No. 1 of 2011
3. Telecommunication Standardization Bureau: “Understanding patents, competition and standardization in an interconnected world”
4. Shrybman Steven, Canadian Centre for Policy Alternative “The WTO: A Citizen’s Guide”
5. Pharmaceutical Industry gets high on Fat Profits http://www.bbc.com/news/business-28212223
6. Stevens. Ashley, Jensen JJ et al “The role of Public Sector Research in the Discovery of drugs and Vaccines” The New England Journal of Medicine (2011);364:535-41
7. Lichtenberg. F, and Sampat B, Assistant Professor in the Department of Health Policy and Management at the Mailman School of Public Health of Columbia University (2011) http://www.news-medical.net/news/20111216/Research-reveals-role-of-government-funding-in-pharmaceutical-RD.aspx
8. http://www.who.int/trade/glossary/story002/en/

Xavier Seuba, Global Health Law Committee of the International Law Association

Submission From: Global Health Law Committee of the International Law Association
Prepared by: Xavier Seuba, CEIPI, University of Strasbourg*

Abstract

The Global Health Law Committee of the International Law Association proposes the adoption of a Framework Convention on Pharmaceutical Innovation, followed by four optional protocols touching upon intellectual property management, funding for innovation, administrative and regulatory tools relating to pharmaceutical approval processes, and international cooperation in science and technology. It builds upon previous projects, and identifies a broad material scope and comprehensive institutional setting.

Health innovation is produced by combination of national and international policies and regulations in a wide array of areas, including health, trade, tax, science and industrial development. Trade-related fields include intellectual property, tariffs, technical standards, regulatory systems, investment, services and subsidies. We propose addressing these aspects in the context of a single regime, composed of an umbrella treaty and four protocols. The Framework Convention on Pharmaceutical Innovation would enshrine the principles informing the technical responses adopted in the protocols, and would identify the relevant stakeholders, the coordination mechanism and the areas of further normative action in additional protocols.

The proposed international regime on pharmaceutical innovation would respond to the multifaceted aspects of medicines’ innovation and access. It would also enhance policy coherence and spur synergies by treating the ‘innovation elements’ in light of the same values and legal principles, including a sound human rights basis. The outline and normative technique implemented would facilitate overcoming technical, scientific and legal difficulties and would ease reaching concrete solutions, as demonstrated in international areas of similar complexity, such as environment, human rights and the law of the seas.

The proposal defines pharmaceutical innovation and portrays it as a common interest of mankind. It also identifies the international legal basis for action in the area of pharmaceutical innovation and access, targets key areas of intervention, and identifies and organizes numerous options to address current deficits in the pharmaceutical innovation system.

Submission

The Framework Convention on Pharmaceutical Innovation and its Related Protocols

Introduction

The Global Health Law Committee of the International Law Association is pleased to submit to the United Nations Secretary-General's High-Level Panel on Access to Medicines a proposal for international normative action to ‘promote research, development, innovation and increase access to medicines, vaccines, diagnostics and related health technologies to improve the health and wellbeing for all’ (UNSG, 2015). It proposes the adoption of a Framework Convention on Pharmaceutical Innovation, followed by optional protocols touching upon intellectual property management, funding for innovation, administrative and regulatory tools relating to pharmaceutical approval processes, and international cooperation in science and technology. It builds, therefore, upon projects put forward by scholars, civil society and states during the last fifteen years (WHO, 2011; WHO, 2012) and proposes a different and broader institutional setting and material scope.

The changing landscape for pharmaceutical innovation

As technological and social changes take place in a rapidly evolving global society, it is necessary to update existing innovation policies, processes and structures. The old linear innovation model has been replaced by a more complex framework, where many actors intervene at several different stages of the innovation chain. Scientific and technological advances, pressing social needs, increased competition and the ever-evolving role of the state, among other factors, have prompted the emergence of innovation models pulling together competences and talents of very diverse stakeholders. More than ever, innovation is highly cumulative and frequently requires collaboration in open, inclusive and enabling environments. As such, innovation reaches unprecedented levels of sophistication. However, contradictory as it may seem, the needs of large segments of the population remain unmet and the overall sustainability of the pharmaceutical innovation system is at stake.

Reflections on the strengths and weaknesses of the pharmaceutical innovation system have been enriched enormously in the last twenty years. The same can be said with respect to the tools that enable innovation. More is known about the complexity of innovation and the need to finely combine many policy, legal and scientific instruments in order to produce innovation. The analysis of these aspects goes beyond this proposal, and the next paragraphs just set the scene of the project proposed to the High Level Panel.

Pharmaceutical innovation refers to the introduction of new products and processes that create value for health. While it is difficult to measure, this definition is a useful starting point. The so-called ‘innovation elements’ encompass varied inputs, processes, legal instruments, finance and economic drivers, policy choices and cultural approaches. Presently, networks of innovators, often of a global nature, have recourse to a wide range of legal and managerial tools of a rapidly evolving innovation toolbox, which must be also observed in the background of specific policy, economic, legal, regulatory and cultural settings. States are sovereign to regulate these elements as they think best. However, there are at least two reasons for international cooperation. First, health is recognized as a legal interest protected by the international community and states benefit from joint action in this respect. Second, innovation is often factually and legally determined by international elements. In this last respect, numerous international treaties pertaining to very different areas are nowadays distal determinants of innovation. 

Numerous tools have been deployed to promote pharmaceutical innovation, mention commonly being made to patents, trade secrets, public funding, pharmaceutical regulatory processes, availability of venture capital, ownership of innovation ‘platforms’ and ‘infrastructure’, science and engineering education, technology transfer, competition, prizes, ‘open’ strategies and liability rules (S. M. Benjamin, A. K. Rai, 2008). This enumeration makes it clear that while pharmaceutical innovation relies on patents, it does not necessarily coincide with what is patentable, a quality which has an autonomous meaning and legal consequences. The multifaceted relationship between patents and innovation, as well as the impact of patents on prices and access to health, has spurred debate on the ‘patent-driven model for pharmaceutical innovation’ (E. Torreele, M. Mazzucato, 2015), a model that may result in undersupply or even in inaccessibility of life-saving pharmaceutical products.

The range of actors in the production of innovative goods mirrors that of stakeholders involved in the policy aspects of innovation. International organizations, states, companies and researchers pursue complementary goals, including the provision of public goods, the maximization of social welfare, the enhancement of firms’ competitiveness and the advancement of science. The promotion of policy options that strengthen such interaction and complementarity is crucial both at the national and international levels.

Framework Convention

Health innovation is governed and produced by combination of national and international policies and regulations in a wide array of areas, including health, trade, tax, science, educational and industrial development. The provision of public goods such as health spans across several legal regimes, notably international health law, human rights law and international economic law. Just to give a measure of the complexity, the concerned trade-related fields include intellectual property, tariffs, technical standards, regulatory systems, investment, services and subsidies.

Previous proposals to set up a treaty on pharmaceutical innovation have been of varying scope and have targeted a wide array of topics, including clinical trials, medical ethics, transparency, open innovation, funding for research and international cooperation on science and technology. Global common values and objectives cut across these proposals and could be enshrined in the Framework Convention on Pharmaceutical Innovation. This general umbrella convention would be inspired by core values and fundamental principles, and would identify the problems, relevant stakeholders and areas of further normative action by means of the adoption of additional protocols. The latter could relate to i) intellectual property management; ii) administrative and complementary tools to foster innovation; iii) funding; iv) international cooperation in science and technology.

The model of a framework convention followed by protocols is frequently pursued in contexts of technical complexity and uncertainty, such as international environmental regimes, or with respect to subjects of high sensitivity, such as human rights. Moreover, it has been implemented in other intrícate contexts, such as climate change and maritime law.

The development of an international regime to foster pharmaceutical innovation would facilitate reaching an initial consensus on a number of central points, such as the portrayal of pharmaceutical innovation as a common interest of mankind and the identification of the areas of relevance to pharmaceutical innovation. Specific and complex areas would then be approached independently, thus facilitating technical discussion on topics of different nature, complexity and constituencies.

A public health and human rights-based global instrument

The proposed instrument would be based on some fundamental principles. First and foremost, innovation in the area of pharmaceuticals is a common interest of mankind. Compelling humanitarian reasons, international human rights compromises, or just self-interest in view of the global health interdependence support that holding.  

A foundation based on human rights is of relevance in this context. Even though some countries have not ratified or accessed to the International Covenant on Economic, Social and Cultural Rights (ICESCR), 164 states are parties to it. It is therefore almost universal in scope, and the work of the Committee on Economic, Social and Cultural Rights, which is in charge of its monitoring, gives it particular global relevance. The right of everyone to the enjoyment of the highest attainable standard of physical and mental health in Article 12 ICESCR provides a useful analytical framework to address practices, regulations and policies with an impact on health. This framework, which has been elaborated further in General Comment 14, builds on two pillars, namely the ‘interrelated and essential elements’ and the legal obligations arising from the right to health. In a nutshell, and in relation to the specific interest of the Framework Convention proposal, states have the obligation to cooperate –including by means of normative action– and to act locally to enhance meaningful and accessible health innovation to prevent, treat and control epidemic and endemic diseases.

            The legal basis for international normative action in the area of pharmaceutical innovation is broader, and includes at least the international fundamental principle of respect and protection of human dignity, which materializes in international compromises to the benefit of public health; Article 55(b) of the Charter of the United Nations and the compromise therein to promote solutions to health-related problems; Articles 25(1), 27(1) and 28 of the Universal Declaration of Human Rights, which recognize the right to health, the right to share in scientific advancement and its benefits, and the right to a global social order where the rights enshrined in the Declaration can be fully realized; Article 15.1(b) of the ICESCR, laying down the right to access to the benefits of science; and Articles 7 and 8 of the Agreement on Trade-Related Aspects of Intellectual Property Rights. Other soft-law texts, in particular the 2030 Agenda for Sustainable Development and the World Health Organization Pandemic Influenza Preparedness Framework are also of relevance.

Protocol on intellectual property management

Fulfillment of the instrumental purpose of the intellectual property system depends on its actual design. Data shows that intellectual property is a tool to stimulate innovation, and proves as well that social norms, government intervention and competition are also vital to enable that function. Accordingly, development of measures relating to intellectual property management could support such a framework.

Patent statutes have commonly adopted broad language with respect to patentability. The room to maneuver needs to be preserved, since it is ultimately related to innovation output, which is both product and country-contextual. In this regard, even if it is implausible to reach international consensus on precise patentability standards and the regulation of infrastructural innovation, it may be worth merely recognizing the lack of consensus.

Next, a reminder of the flexibility existing with respect to post-grant measures of relevance to innovation would be also meaningful. The measures include, among many others, the research exception, patent opposition procedures and non-voluntary licenses in cases of patent dependency, each of which has national contextual aspects. In the Framework Convention these references may be broad and merely quote the Doha Declaration on the TRIPS Agreement and Public Health, whereas more detail could be provided in the suggested protocol on intellectual property management. In this same context, patent approval processes may also be enriched, for instance by giving special status to patents relating to priority health needs.

Open innovation models, based on cooperation to foster the development of knowledge and economic growth, rely heavily on intellectual property management and balancing of stakeholder incentives. In this sense, new approaches to intellectual property sharing and management, and some arrangements previously considered anticompetitive, such as patent pools, are currently instrumental to promote efficiency and cooperation. Successful international models include the Medicines Patent Pool which could be supplemented by a number of key principles to adjust intellectual property management to contemporary values and needs, in particular transparency with respect to patent status and licensing conditions. Likewise, the impact of other intellectual property categories on innovation, as well as the relationship between intellectual property rights and subsidies, should be addressed in the context of the negotiations.

Protocol on pharmaceutical innovation financing

            In 2012, the Consultative Expert Working Group on Research and Development developed detailed ambitious proposals for financing innovation, in particular the identification of a sustainable source of funding. The proposals of the Working Group, and the discussions that followed, could be the starting point for the ‘financing protocol’ of the Framework Convention on Pharmaceutical Innovation. They included discussion on a ‘governmental agreement to contribute to the global cost of R&D, considering each nation’s level of development, size of economy and capacity to pay’ and delinkage between the costs of innovation and the price of pharmaceuticals, a key concept bridging access and innovation.

Whether the funds collected would be devoted to prizes, grants or directly publicly-funded research should be addressed in the protocol. In that regard, direct subsidization has been identified as the most effective response to inadequate innovation incentives and costly adaptation (K. Maskus, 2015). In this regard, international norms on subsidies (the WTO Agreement of Subsidies and Countervailing Measures) may be relevant. Likewise, the protocol should set up the requirement that major changes in innovation-related policies are subjected to cost-benefit analyses and the collection of robust data supporting the recommendations. While economic and analytical outputs cannot replace public policy priorities, they are instrumental in identifying and designing the best tools to stimulate innovation.

Protocol on administrative and technical measures

Medicines’ regulatory agencies and entities responsible for financing drugs play a relevant role in innovation policies. Because of their specificities and the topics of regulation (technical standards, medicines purchasing) they deserve independent attention.

On the one hand, there are policy, governance and normative aspects relating to international quality, safety and efficacy of medicines that need to be addressed. In particular, the inclusiveness and openness of some international standard-setting processes and the way certain standards may impact the development of new drugs must be addressed.

On the other hand, a range of instruments and measures normally implemented at the national level could gain additional recognition in an international treaty. These instruments and measures include procurement agreements, advanced market commitments, conditions of access to government funded research, priority review vouchers, and free access to test data information.

Protocol on science and technology cooperation

International scientific cooperation is key to fulfill the potential of pharmaceutical research. Proposals on the adoption of an international treaty to facilitate and promote the development of science and technology have been on the table for the last two decades (J. H. Barton, 2002; J. Love, T. Hubbard, 2004). Numerous bilateral agreements and scientific programs like the European Union Horizon 2020 already promote scientific and technological international cooperation, and may be a source of inspiration and funding.

The relevant protocol could address i) rules on research subsidies in areas of public health interest; ii) an agreement to place ‘into access pools the patented results of publicly funded research that develops knowledge capable of supporting applied science and R&D, especially in areas of common global concern’ (K. Maskus, K. Saggi, 2015); iii) measures enabling cooperation between research centers; iii) compromises to facilitate international mobility of scientists, for instance by expanded Mode 4 commitments in the General Agreement on Trade in Services; iv) design of agendas of common interests and priority setting in accordance with public health priorities; v) measures to stimulate technology transfer between developed and developing countries; vi) criteria to support publicly funded research; vii) regulation of conditions for accessing publicly funded research or tax advantages; viii) facilitating access to scientific resources; ix) development of co-funding and joint-funding mechanisms.

Which international structure and adoption process

An instrument of this caliber needs broad international support, including states with research-based economies, emerging economies, as well as countries with pressing health needs. It also requires involvement of numerous international organizations, companies supplying different segments of the pharmaceutical market, scientists, and health organizations.

Prior complex international normative processes were materialized through a range of conferences over a considerable number of years. In the case of pharmaceutical innovation, discussion has advanced since the nineties. On the one hand, discussions relating to the adoption of a treaty have taken place for the last 15 years and have progressed in many respects. The proposal put forward aims at providing the structure and mechanisms, and some update, to proposals previously made. On the other hand, numerous already existing initiatives, developed by multiple stakeholders in international organizations, civil society, the private sector and academia, could fall under the scope of the new regime. The task would be twofold: coordinating and going further when necessary, while constructing broad-ranging stakeholder incentives to participate.

International organizations and organisms that must be involved in this process include the World Health Organization, World Trade Organization, World Intellectual Property Organization, United Nations Industrial Development Organization, United Nations Conference on Trade and Development, United Nations Children’s Fund, the Office of the United Nations High Commissioner for Human Rights, and United Nations Development Programme. In addition, perspectives from global health stakeholders including NGOs, private sector researchers, developers, and manufacturers, donors, member countries and medicines procurement agencies will play a critical role to inform these discussions.

The Framework Convention, negotiated in the context of international conferences, could establish a light coordination mechanism or authority in charge of coordinating or monitoring the action of concerned stakeholders. The coordination mechanism could be based on the recommendations put forward by the Consultative Expert Working Group on Research and Development and stakeholders described herein, and could also benefit from the experience of small and functional international authorities and normative processes, such as the International Seabed Authority or, provided necessary changes are made in order to ensure representativeness, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, or similar technical or regulatory groups. 

Notes, Bibliography and References

* The perspectives in this submission may not necessarily reflect the totality of views of each member of the GHLC. It is intended to further public dialogue and the development of needed options. Peter Beyer, as current staff at WHO, has recused himself from this submission. Frederick Abbott, co-chair of the GHLC, is a member of the Expert Advisory Group. For the Members of the Committee, see http://www.ila-hq.org/en/committees/index.cfm/cid/1053/member/1)

J. H. Barton, ‘Integrating IPR Policies in Development Strategies’, Stanford University ICTSD-UNCTAD Dialogue, The Rockefeller Foundation’s Bellagio Conference Center, 30 Oct.-2 Nov. 02, p. 3

S. M. Benjamin, A. K. Rai, ‘Fixing Innovation Policy: A Structural Perspective’, The George Washington Law Review, vol. 77, 2008, p. 2

T. Hubbard T, J. Love, ‘A new trade framework for global healthcare R&D’, PLoS Biol 2004: 2(2): e52. doi:10.1371/journal.pbio.0020052

K. Maskus, Research and Development Subsidies: A Need for WTO Disciplines?, E15Initiative. Geneva: ICTSD&WEF, 2015.

K. Maskus, K. Saggi, Global Innovation Networks and their Implications for the Multilateral Trading System, E15Initiative, Geneva: ICTSD&WEF, 2015.

E. Torreele, M. Mazzucato, ‘Ensuring needs-driven R&D that Maximizes Health Impact in a Cost-Effective Way’, in Rethinking the Economics of Pharmaceutical Innovation. Background Reading, OSF, October 27 & 28, 2015, pp. 3-6.

UNSG High-Level Panel on Access to Medicines, Terms of Reference, 2015, point 6.1.

WHO, Global Strategy and Plan of Action on Public Health, Innovation and Intellectual Property, 2011, 28 (2.3) (c)

WHO, Research and Development to Meet Health Needs in Developing Countries: Strengthening Global Financing and Coordination, Report of the Consultative Expert Working Group on Research and Development: Financing and Coordination, 2012.

Nthabiseng Meriam Mabokang Sekokotoana, Lesotho Ministry of Law

Name of Lead Author: Nthabiseng Meriam Mabokang Sekokotoana
Organization: Attorney-General's Chambers: Office of Parliamentary Counsel, Ministry of Law
Country: Lesotho

Abstract

Lesotho, like most countries, recognizes the need for protection of health and appreciates its obligation to ensure that access to medical services and improvement of public health is provided for all.1 It is through this recognition that Lesotho formulated a Health Policy which ensured that its citizens would get access to public health. The question however is how effective is the policy, how harmonized is it with other sectors which may influence and affect the effectiveness of its objective and how coherent is its regulatory framework in addressing challenges such inadequate innovation of successful health technologies which may be hampered by research and development, affordable national capacity to develop appropriate policy and regulatory framework.
Lesotho has further developed a regulatory framework which envisages addressing the need to protect public and ensure access to health by developing a draft Bill on Medicines and Medical Devices. Further questions arise, how coherent is this framework with other sectors of government and how complaint is it with the recognition of intellectual property rights, such as Patents as envisaged under international treaties to which Lesotho is a party to, such as the Trips Agreement 2.

Contributions made against this background are conducted from a perspective of Parliamentary Counsel (PC). PC’s core function is to translate and transform government policies into law by drafting government legislation. The author is currently charged with the responsibility of drafting the Medicines and Medical devices Bill and is also responsible for drafting intellectual property legislation in the country.
In performing this function, the author seeks to contribute by indicating how if properly engaged Parliamentary Counsels play a pivotal role in ensuring coherence among various government policies. The author thus envisages addressing how the misalignment encountered or existing between rights of inventors, human rights, law, trade rules and public health can be overcome.

A brief explanation of Parliamentary Counsels role of transforming government policies into law will be discussed in line with how it can assist in reducing incoherence in rules between rights of investors, international human rights laws, trade rules and public health objectives by outlining processes and procedures that need to be strictly followed by countries amended.Secondly, a case study of Lesotho’s current status and some of the initiatives taken will be looked at. Lastly, a conclusion will be drawn and recommendations will be made. 1. Lesotho Constitution 1993 as amended.

Submission

Countries recognize the importance of public health related innovations and inventions and the need for citizens it access to them. To attain this, countries need to develop policies and laws that establish regulatory frameworks which will effectively address the recognized objective. Various sectors are involved in such initiatives like health, law, trade, environment, human rights or agriculture, universities and science and technology departments to name just a few. As a result when formulating policies and laws it is imperative to have a well outlined coordination among these sectors to enable coherent and effective functioning. Truth be told, such coordination is difficult to realize and it creates a huge hurdle for the better functioning of government to enable it to meets its objectives. PCl can, through the skills imparted on them, be entrusted to remove such hurdles of policy incoherence.

During formulation of legislative and regulatory frameworks, which for the purpose of this contribution is earmarked as one of the important pillars of addressing challenges encountered to improve and provide access to public health and promoting research and development and innovation for related health technologies, PC is mandated to ensure that there is a well coordinated and thoroughly thought out policy in place.

2. Trade Related Aspects of Intellectual Property Rights Agreement1994.
Parliamentary counsels’ fundamental role is to ensure that government policies are transformed into law and are given legal effect so as to enable successful implementation of the legislation. In order to effectively perform this function, it is worth to note that Parliamentary counsel possess the unique drafting and legal skills which enable extensive experience in offering advice during policy formulation. One of the most important skills PC possesses relevant for the purposes of addresses incoherences in policies is that of having the ability to ensure compatibility with other legislation. This means that PC interacts with various stakeholders and deals with a wide range of issues and areas of national importance. PC then is one of the key people who can identify relevant stakeholders both who are in the health sector and those who are either directly or indirectly affected or related to health issues such as trade, agriculture, environment, law and human rights to name but just a few.

On this background, PC highly appreciates the need for thorough consultations during policy formulation because she knows that through such consultations, clarity is attained and conflicts avoided. Suggestions are made that maybe to overcome this hurdle, governments should provide time. A requirement mostly overlooked because political objectives often come with flag tags of “urgent” formulations of policies which are either incomplete, “copy and pasted” from other jurisdictions or are non-existent and yet proposals are put forward for developing legal or regulatory frameworks. The resulting effect is always unharmonised policies which makes it difficult for implementation.

Such consultations if properly conducted, they can avoid incoherences because it is at this stage where thorough understanding of and the extensive analysis of the policy proposal is dealt with. PC, with the expertise and specialist skills acquired through training is able to advice on the best approach to be chosen which would eventually give the policies the legal effect it envisages. It is also at this juncture that the author believes countries should deeply consider utilizing the Regulatory Impact Assessment (RIA) tool. Lesotho is in the process of considering requesting this tool to be a compulsory requisite from ministries to prove that during policy formulation they conducted the RIA. This tool assists in governments deciding which option is best suited to address the problem faced and ensures efficiency and practicability in implementation because in most cases wrong approaches for problems are sought out. For instance in a case of access to medicine, when we discuss the issues of affordability, one would argue that is pricing and patent a case protection the significant problem that requires to be solved and is legislation the appropriate solution or is the problem more of careless administration of medicines where incorrect dosages are given may lead to resistance of those medicines? So would the problem not be that of health services provider’s attitudes or ignorance which now would be more of in-depth training of such which may not necessarily be addressed through regulation? RIA therefore helps identify the actual problem that needs to be attended and the correct solution to the actual problem. Maybe another example to illustrate this point would be the case of medicines containers where it was believed that children were dying due to the easy caps attached to medicine bottles. To address this problem a policy was put in place to obligate manufactures to produce caps which would be hard for children to open and came up with the press-push and twist caps. A child upon realizing that she could not open the bottle started out of frustration banging the bottle and to her satisfaction the bottle opened and she gladly took her dosage of the medicine. So in this scenario, it is realized that the real problem here was not the caps but accessibility of medicines where parent left them within the visibility and reach of children. The real solution to this problem was therefore a matter of public outreach than It is therefore imperative to involve PC as a strategy to avoid policy incoherences because PC is, “ an architect of social structures, an expert in the design of frameworks of collaboration of all kinds of purposes ,a specialist in the high art of speaking to the future, knowing when and how to try and bind it and when not to try at all. The difference between a mechanic and a legal draftsman turns largely on an awareness of this point ”3.

Some of the mechanisms and initiatives made by the author’s jurisdiction in an effort to minimize and try to overcome hurdles of incoherent policies are amongst others the attendance of an African Regional Meeting held in Ethiopia on Promoting Policy Coherence for Health Technologies-Access and Innovation Consultative Forum with particular emphasis on policy coherence and coordination within the national, regional and international level for laws and policymaking affecting access to and innovation of health. In this meeting a presenter from the EU5 shared with us the Pharmaceutical manufacturing Plan for Africa which recognized the need for local production on pharmaceutical products throughout Africa and also that the “production of quality medicines and the development of an international GMP compliant industry in Africa is possible, desirable and eminently doable”. This plan further recognized that countries in the region should align themselves with the African Medicines Regulatory Harmonization Program so as to ensure quality, safety and efficacy and most importantly, create harmonization of medicines frameworks. The author is proud to mention that Lesotho has aligne herself wi.th the framework during the development of the Lesotho Medicines and Medical Devise Bill, 2016. Furthermore TRIPs flexibilities were also discussed and Lesotho regards such opportunities as highly useful in improving access to health technologies and is in the process of incorporating such flexibilities for the benefit of its nation.

Another strategy that was discussed at the meeting which the author believes is worth sharing is the the Zambian case study, and which Lesotho also seeks to adopt and is the preliminary stages, where Zambia established a national Multi-Stakeholder Working Group and a Ministerial Working Group. This strategy is seen as an effort that would also assist with improving policy coherence. Lesotho has since C established the Inter-Ministerial Committee which is currently developing its terms of reference. Its is hoped to be a success story which will help improve and promote access to health while at the same time complying with, recognizing and protecting international obligations, the right to health and intellectual property rights.

Lesotho through a private mobile network company, Vodacom Lesotho, in collaboration with the Ministry of Health, has initiated a project known as Mojo. The main objective of this project is to identify and provide treatment for children between the ages of 0-14 who are infected with HIV. To achieve this objective, the project uses a mobile application given to nurses across the country to enable them to capture data and link the patient’s data to health care such as village health workers so as to enable patients to get referrals to appropriate facilities as and when need arises. The applications are technology based and are said to assist with monitoring and managing patients data which will enable access to the required treatment because accurate patient data will have been captured. Through this strategy, mobile outreach programs were made where they facilitate mobile money services that enable and access health. Furthermore through the Mojo project, patients are given transport vouchers to assist them to travel to clinics. An observation made however is patients sometimes even when they are given transport vouchers, they do not go to clinics as expected. A major observation made , which is believed may hamper access to and improve health care is lack of a competent management health system. It is believed this is the area of concern which needs major creativity in terms of how it will be addressed because evidence has indicated that even where services are free, access is still a challenge. Maybe extensive training should be provided and more payment given to the nurses and other health providers among other solutions. Furthermore, it has been suggested that the public needs fully intergrated health care because it is more patient focus than being disease based.

Another initiated strategy which may address the challenges of inadequate research and development and innovation is an establishment of a centralized focal point for science and technology for all those relevant ministries and stakeholders. In Lesotho, the Department of Science and Technology in in the process f facilitating enactment of the Science and Technology Bill, 2016 into law which seek to establish a Science and Technology Commission as such a focal point and coordinating body on science and technology issues for all sectors. Within the proposed law, there is a provision which also establishes an innovation fund whose objective is to encourage people to innovate by assisting with funding potential innovators. The potential innovators will submit proposals to the Commission for assessment and determine which proposals have the potential to solve problems encountered by society and then award small grants to the potential innovator to pursue further research and development because funding is seen as a major hindrance for promoting research and development. The proposed law further establishes an Appropriate Technology Centre which serves more as an implementation where new technologies are tested and validations made. This would also seek to address the challenge of lack of resources, especially laboratories to enable local innovation to take place. A proposal is also encouraged of establishing a Cabinet Committee on Science and Technology which would ensure coherence at the level of the executive which would facilitate acknowledgement and promotion of access to services like health through promoting, research and development and innovation.

Another challenge the department felt hinders innovation is the fact most institutes seem to be more teaching based than research based. For instance, our national University does offer any PHD programs at institutes because it seems to be diverted elsewhere to other commitments. It is also indicated that initiatives such as the Horizon 2020 which through it the department was able to send a scientist from Lesotho to South Africa to take samples of traditional medicines to be tested and validated for the treatment other HIV//AIDS infections. Those samples were also taken to Switzerland for further analysis and the results are said to be promising because there has been a certain percentage of the samples which have shown a direct impact on the actual virus than just improving the immune system. Further test and analysis of the traditional medicine are yet to follow. This occurrence is very interesting because it also raises issues of intellectual property law of the growing concern of protection of traditional knowledge. Another initiative known as SANBIO is seen as another strategy to be utilized for promotion of research and development in that it encourages proposals to be submitted for assistance in funding and facilitating further research. As a result health Committee was established which meets monthly to discuss health issues related to innovation. The committee has formulated a spreadsheet which they say is sent to institutes and requests them to submit lists of areas of interest.

Establishment of a central coordinating body was a sentiment shared by a lecture from one institute . He believes such a strategy would be the most viable solution to address the challenge of inadequate research and development because he also says funding and lack of resources greatly hampers learning and of students to research because teaching is concentrated more on theory than practical’s. The lecturer further indicated that as an effort to enhance research and development at the institute there is a proposed development plan that the institute envisages to utilize. He also proposed that maybe if the institute could merge engineering programs offered at the institute which are electrical and mechanical tand detailed.

Students consulted also felt lack of resource hampers their learning and innovation capabilities . The student indicated that they feel less motivated because of a seemingly ignorance of their innovation which leaves their efforts made during their learning years unacknowledged. They suggested that maybe if after completion of their studies they could placed at incubation centres like the one currently established by the mobile company Vodacom Lesotho known as Innovation Park. This they said hinders them from engaging in further research. The further reiterated that because of lack of resources they fund their own projects and as a result, even if they have a certain idea and it appears to be costly, they feel it is better to abandon their preferred idea and opt instead for something less costly for fear that if they pursue their preferred idea they will fail. So clearly students feel less encouraged to research and invent innovations that rare more useful for the benefit of the nation and this says focus for students are more survival based than passion and talent based. An worrying perception which requires urgent attention.

If a country does not have a healthy productive nation, then the economy will wither too. Policy coherence and a well coordinated legal and regulatory framework needs to be put in place to ensure that they harmonized by having a committed nation and leadership which seek to address reasons anticipated are contributing to the existence of challenges identified. 

Recommendations
Although Parliamentary Counsel does not initiate policy, it is highly recommended that it is imperative to involve the because of the specialist expertise they posses which would extensively assist in ensuring policy coherence due to their vast knowledge of existing laws. As a result, they interact with various sectors and are therefore have the potential of being able to identify relevant stakeholders who would be affected by health issues raised. The need for adoption of pharmaceutical manufacturing plans and harmonization regulatory frameworks cannot be emphasized enough. Furthermore the Zambian case study should be followed of establishing a National Health Multi Stakeholders Working Group and lastly, the author thinks the use of mobile application to improve access is a phenomenal strategy to be adopted.

Bibliography and References

1. Constitution of Lesotho 1993 as amended.
2. Dee Harlow, Head of Lesotho Pediatric HIV Program, Vodacom Foundation, Maseru, Lesotho.
3. Janet Byaruhanga,AUC:The African Union Pharmaceutical Manufacturing Strategies for initiating and sustaining local production capacity in Africa.
4.Rasekeiti Mohlomi, Keneuoe Morake, Ramabusa Thabo Nkoho Rethabile all who are 6th Semester final year Electrical Engineering Students.
5.Tladi Manosa, Lecturer of science and maths at Lerotholi Polytechnic Institute, Maseru, Lesotho. . Trade Related Aspects of Intellectual Property Rights Agreement1994.
6. Ts’epo Ntho, Senior Research Officer, Department of Science and Technology Lesotho.
7. V.C.R.A.C.CRABBE:Legislative Drafting 1st Ed P21,1993 London.

Ellen 't Hoen, Global Health Law Committee of the International Law Association

Submission to the UN High Level Panel on Access to Medicines by the Global Health Law Committee of the International Law Association.

Prepared by: Ellen ‘t Hoen LLM, Prof dr Brigit Toebes, Katrina Perehudoff MSc, LLM, and Prof Frederick M Abbott
 

Abstract

The Global Health Law Committee of the International Law Association appreciates the opportunity to submit proposals to the UN High-Level Panel on Access to Medicines to address the misalignment between the rights of inventors, international human rights law, trade rules and public health where it impedes the innovation of and access to health technologies.*

The right to essential medicines is a key component of the right to health as guaranteed under international human rights law. Essential medicines should be available, accessible, acceptable and of assured quality.

We recognise that addressing IP related challenges to access to medicines is but one aspect of medicines policies that need to be in place to ensure effective medical treatments of assured quality are available.

However, there is an embedded conflict between government obligations under human rights law to ensure access to medicines and obligations under intellectual property law to grant medicines patents.

A global public policy response that rebalances obligations under human rights law with obligations under IP law is needed.

We wish to submit the following proposals that would contribute to realigning rights and obligations under human rights and intellectual property law and contribute to reaching the Sustainable Development Goals (SDGs).

1. Establish an Essential Medicines Patent Pool through which licences are available to guarantee generic production and availability of quality assured essential medicines.

2. Support effectively automatic non-voluntary licensing of patents related to medicines on the WHO Model List of Essential Medicines or their national essential medicines list by national governments.

3. Authorize exemption of essential medicines from patenting through an authoritative interpretation of articles 27 and 30 of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights.

This submission offers a summary of the proposals. We recognise that substantial additional work is required to develop the proposals in detail.

Submission

1. The WHO Essential Medicines Concept and the challenges of ensuring access to new Essential Medicines as a component of the right to health in a post TRIPS era.

The right to essential medicines is a key component of the right to health as guaranteed under international human rights law. The most important treaty is the International Covenant on Economic, Social and Cultural Rights (ICESCR, 1966) enshrining the right to health in Article 12.** This provision is further interpreted in the non-binding yet authoritative General Comment 14 (2000), which defines the State’s legal obligation to provide essential medicines.

According to the WHO, essential medicines are: ‘[T] hose that satisfy the priority health care needs of the population.... selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness… [and] intended to be available within the context of functioning health systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality and adequate information, and at a price the individual and the community can afford’[1].***

The WHO published the first Essential Medicines List (EML) in 1977 and has updated the list every two years. The WHO EML guides countries in the selection and provision of essential medicines. Countries are encouraged to develop their own EML and to implement policies to ensure access to these medicines. Today, more than 150 countries have an EML [2].

Access to essential medicines is a key component of the fulfilment of the human right to health. A study of 186 national constitutions shows that 135 (73%) include provisions on health or the right to health. Some constitutions specifically mention access to medicines [3]. The SDGs include achieving Universal Health Coverage (UHC) and emphasise access to essential medicines and vaccines for all [4].

Essential medicines should be available, accessible, acceptable and of assured quality [5]. Essential medicines policies have traditionally been rooted in policies to encourage the availability of generic medicines. Countries have sought to keep the prices of essential medicines low by excluding them from patentability. The Andean Community, in 1991, adopted a decision providing that “inventions related to pharmaceutical products included in the List of Essential Drugs of the WHO” shall not be patentable [6]. India excluded medicines from patentability until 2005 [7].  This encouraged the development of a generic pharmaceutical industry that has served as the ‘pharmacy of the developing world’ [8]. When the Uruguay Round of trade negotiations was launched in 1986, 49 of the 98 parties to the Paris Convention excluded pharmaceutical products from patent protection [9]. Countries varied in the periods of protection granted and/or set out conditions that restricted patent holders’ rights [10].

Adoption of the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) in 1994 diminished the legal space through which the availability of generic medicines might be assured. TRIPS set out minimum standards for the protection of intellectual property rights. Members of the WTO may no longer exclude entire fields of technology, such as medicines, from patentability,[11] and a minimum 20-year patent term is obligatory [12].

The 19th EML edition (2015) contains several important medicines including for the treatment of cancer, tuberculosis (TB) and hepatitis C (HCV) that are widely patented and highly priced [13]. The high prices of the new essential medicines illustrate the challenges to access in the post-TRIPS era [14]. When WHO labels a medicine as essential governments must act to ensure availability.

Yet, mandatory patenting of new essential medicines has entrenched price-setting power within the commercial industry, reducing the effective authority of governments. Monopoly pricing routinely precludes wide access. There is an embedded conflict between government obligations under human rights law and obligations under IP law.

2. Political coherence of States’ obligations under international intellectual property treaties and obligations to ensure the human right to health.

The introduction of TRIPS coincided with the emergence of the HIV/AIDS pandemic, which fuelled a global campaign for access to medicines [15].

The global mobilization around HIV focussed on a number of flexibilities contained in TRIPS to bring down the price of medicines. These flexibilities include compulsory licensing (CL), parallel importation, delay and/or non-enforcement of medicines patenting and regulatory data protection by least developed countries, defining patentability criteria to reward meaningful innovation and prevent ‘ever-greening’ of patents, and implementing exceptions to patent exclusivity.

In 2001 the WTO adopted the Doha Declaration on TRIPS and Public Health expressly acknowledging these flexibilities and making clear that IP protection must not interfere with the protection of public health [16]. Paragraph 4 reads: “We agree that the TRIPS Agreement does not and should not prevent Members from taking measures to protect public health.  Accordingly, while reiterating our commitment to the TRIPS Agreement, we affirm that the Agreement can and should be interpreted and implemented in a manner supportive of WTO Members' right to protect public health and, in particular, to promote access to medicines for all.”

Consistent with the Doha Declaration, developing countries that had ARV patents have widely used TRIPS flexibilities to procure generic ARVs, mostly from India where these products were not patented. In 2010 the Medicines Patent Pool was created to ensure that generic versions of new ARVs continue to be available. Today, first line ARV regimens are available from generic suppliers for US$ 95 – 158 [17], a steep decrease from US$ 10.000 - 15.000 a decade and a half ago. It is estimated that 80% of the people receiving HIV treatment access generic prequalified ARVs. This progress is the result of unprecedented global mobilisation and the absence of medicines product patents in India until 2005.

The use of flexibilities for non-HIV products seems to be more difficult and politically more sensitive. For example when India issued a CL for a cancer medicine it provoked an out-of-cycle review by the US Trade Representative [18]. The MPP has recently expanded its mandate to include HCV and TB, but challenges remain for countries outside the scope of the MPP agreements. For other new essential medicines such regularized access strategies are lacking.

TRIPS-plus requirements (i.e. standards of IP protection higher than those mandated by TRIPS) in regional and bilateral trade agreements roll back much of the positive momentum represented by the Doha Declaration [19]. Investor to State Dispute Settlement (ISDS) mechanisms, often contained in such agreements, are being used by the pharmaceutical industry to contest decisions by national patent offices and courts [20].

The trend in international norm setting for patents reflects the IP agenda of corporations that seek expansion of their monopoly positions in the market through patents and other market exclusivity mechanism. For example: test data protection rules that prevent the marketing authorisation of generic and biosimilar medicines by a medicines regulatory agency for a certain period of time or marketing exclusivity granted under orphan drug laws.

The progress in access to ARVs has been the result of a unique and unprecedented global mobilisation. Other diseases have not sparked responses at the same scale, which raises the question of how to ensure access to new treatments for hepatitis, tuberculosis (TB), cancer, diabetes and other non-communicable diseases in the face of expanded patent and exclusivity rights.  Affordable essential medicines are crucial to the success of UHC, an important target under the SDGs.

3. The human right to access to essential medicines – who is responsible for the fulfilment of this right?

Obligations of States parties

States are the primary duty holders under the international human rights treaties. Based on Article 12 ICESCR, they are under a legal obligation to take measures necessary for the prevention, treatment and control of diseases and for creating conditions assuring access to medical services [21]. General Comment 14 explains that States should ensure that medical services, including essential medicines, are available, accessible, acceptable and of good quality (‘AAAQ’) [22]. It identifies access to essential medicines as a legal core obligation of the right to health [23]. According to General Comment 14, the legal core obligation to provide essential medicines is 'non-derogable', which means that non-compliance would result in a prima facie violation of the ICESCR [24]. They are also under a legal obligation to ensure that the pharmaceutical industry does not limit people’s access to essential medicines (State’s ‘obligation to protect’) [25].

Obligations of the international community of States

States and the international community of States at large are under an obligation to facilitate access to essential medicines in other countries and to provide the necessary aid when required [26]. They are to assist developing countries in realizing their core obligation to provide access to essential medicines to their population [27]. States should prevent third parties, including the pharmaceutical industry, from violating the right to health in other countries [28]. They should ensure that their actions as members of international organizations take due account of the right to health [29].

Responsibilities of the pharmaceutical industry

The preamble to the Universal Declaration of Human Rights calls on ‘every individual and every organ of society’ to promote and respect human rights. Similarly General Comment 14 recognizes that the private business sector has responsibilities under the right to health [30]. In line with this it is widely recognized that the pharmaceutical industry carries responsibilities under the right to health [31]. Based on the ‘Ruggie Principles’ (2008), endorsed by the Human Rights Council in 2011, pharmaceutical companies have the corporate responsibility to respect human rights. This means that they should avoid infringing on the human rights of others and should address the adverse human rights impacts of the activities in which they – or their business relationships – are involved [32].

Enforcing responsibilities to the human right to health

The tension between IP and human rights is perpetuated by the differences in how these two frameworks are enforced. IP rights enjoy binding enforcement mechanisms at the international level through the WTO Dispute Settlement Mechanism and through ISDS. While both IP and human rights standards are legally enforceable and binding on State parties, the authority of human rights norms is not often recognised within the IP framework. Although WTO dispute settlement no longer insists on a self-contained regime approach, human rights have yet to play a material role. On the other hand, States are held accountable to human rights norms in several authoritative, albeit often non-binding, fora (i.e. CESCR).

Access to medicines as part of the human right to health has been increasingly enforced before domestic courts, with one of the most prominent cases filed by the Treatment Access Campaign seeking access to ARVs in South Africa [33]. Domestic enforcement is highly contingent on a functional national judiciary and patients’ own access to justice - both of which may be lacking in countries where access urgently needs to be scaled up. In successful cases where patients cannot afford their medicines, the courts often shift the financial burden from the patient to the State, which must pay for expensive, sometimes patented, medicines, rather than address the root causes of high prices. For example in Brazil, where unplanned government spending on court-mandated medicines grew by 11 times over 2 years, reaching US$47,8 million in 2009 [34]. In these circumstances, achieving UHC and health system sustainability becomes a major concern.  These shortcomings show that a more equitable solution is needed to address the core issue of how health systems can provide high-priced, essential medicines rather than ease only the symptom of patient affordability through the courts.

A global public policy response that rebalances obligations under human rights law with obligations under IP law is needed to address patent challenges to access to new essential medicines.

4. Proposals to realign obligations under human rights treaties and IP treaties.

Access to essential medicines is a key component of the right to health. Essential medicines should be available “at a price the individual and the community can afford” [35]. The patent status of an essential medicine can be an impediment to achieving an affordable price and to a government’s obligation to fulfil its population’s right to essential medicines. This is the case when the patent holder refuses cooperation through equitable pricing or licensing of the relevant patents.

We recommend realigning obligations under human rights treaties and IP treaties by ensuring that effective mechanisms to overcome patent barriers to access to essential medicines are in place.

We therefore make the following proposals aimed at reconciling access to essential medicines under the right to health and patent rights for consideration by the High-Level Panel:****

1. Establish an Essential Medicines Patent Pool (EMPP) under the auspices of the UN.

The EMPP could be modelled after the MPP and pursue public health focused licence terms and conditions [36, 37]. The unmet need for treatments for both communicable and non-communicable diseases justifies the application of the patent pool model beyond only a few infectious diseases.

Companies should license their patents related to essential medicines to the EMPP, which would align with their responsibility to promote and protect human rights.

Both voluntary licensing and CL (Proposal 2) through an EMPP should be coupled with a tiered royalty system to remunerate the patent holder and contribute to R&D expenditure at levels proportionate to GDP. The WHO and UNDP have provided guidelines for the remuneration of non-voluntary use of medical technologies that could be used or further adapted for that purpose [38].

A patent owner’s refusal to license an essential medicine to the EMPP would satisfy the CL grantee’s requirement under article 31 to have made efforts to obtain authorization from the right holder on reasonable commercial terms and conditions, recognizing that there is no prior negotiation requirement in cases of national emergency, extreme urgency or public non-commercial use.

The right of states to exempt essential medicines from patenting should be authoritatively recognized by the WTO (Proposal 3), including taking into account obstacles that could arise in the implementation of the EMPP. This would assure that the priority needs of individuals, in accordance with basic human rights principles, are given first priority among interests.

2. National governments should establish effectively automatic non-voluntary licensing of patents related to medicines on the WHO EML or their national EML.

The UN and its specialised agencies in collaboration with the WTO should develop guidance for countries including model legislation to implement the effectively automatic provision of CL for essential medicines. This effectively automatic non-voluntary system should be implemented immediately and should be integrated with the EMPP when the latter is established.

Compulsory licensing of patents related to essential medicines is possible under TRIPS. The Doha Declaration specifies: “Each Member has the right to grant compulsory licences and the freedom to determine the grounds upon which such licences are granted.” While Article 31 (a) of the TRIPS Agreement requires that CLs should be considered on their individual merits, a legal mechanism meeting that requirement may employ identification as an essential medicine as the means through which the individual merits of a licence are determined [39] [40]. Export of the predominant part of essential medicines produced under such a CL should be understood to fall within the August 30 2003 ‘waiver’/pending amendment inserting article TRIPS 31bis, satisfying the requirement for authorization of export of medicines produced under a CL.

3. Authorize exemption of essential medicines from patenting.

The WTO Ministerial Conference should provide an authoritative interpretation of articles 27 and 30 of TRIPS to allow Members to exclude essential medicines from patentability. The UN General Assembly should adopt a resolution urging the WTO to take this action.

The priority needs of individuals for access to essential medicines should take precedence over commercial interests, and should be facilitated. The recommended authoritative interpretation would demonstrate unqualified recognition by the international community of the priority of human rights over commercial interests.

5. Conclusion

Impact on policy coherence and advancing human rights

All three proposals will increase policy coherence by strengthening the human rights aspects of access to medicines and by providing effective remedies to patent barriers to generic low-priced essential medicines.

Impact on public health

The impact on public health is expected to be significant. High prices are a serious impediment for providing new essential medicines as is evidenced by the global rationing of new antivirals for the treatment of HCV, challenges of access to new ARVs in countries excluded from voluntary licence agreements and the lack of cancer treatment. While affordability is only one aspect of ensuring access to medicines, lack of affordability is often the single most important barrier.

Implementation

Proposal 1: Establish an Essential Medicines Patent Pool.

An EMPP can be modelled after the MPP, or established in collaboration with the MPP and does not require legislative changes. The MPP has enjoyed the cooperation of the industry, suggesting that stakeholder support could be expected for an EMPP. An EMPP offers the industry a mechanism to honour its human rights responsibilities.

The establishment of an EMPP under the auspices of the UN would give it a sustainable organisational and financial base and ensures involvement of States. This will help create a synergy with the implementation of Proposals 1 and 2, which require the involvement of governments.

Proposal 2: National effectively automatic non-voluntary licensing of patents related to essential medicines.

Proposal 2 can be implemented by national governments without further changes in the international IP legal framework. The fact that some countries have started to grant CLs for cancer and heart disease medication may indicate growing political willingness for broader application of CL. Strong technical, legal and political support from relevant UN and international agencies will enhance uptake of this proposal.

Proposal 3:  Authorize exemption of essential medicines from patenting.

Authoritatively authorizing exemption of essential medicines from patent subject matter coverage provides a global solution, is predictable and long-term. This will not address the potential impact of TRIPS-plus rules, but it will send a persuasive normative message.

Implementing this recommendation will require cooperation at the WTO. Today the political commitment of WTO Members to implement this proposal may be weak. It will therefore be important that the UN make the recommendation to authoritatively authorize exemption of essential medicines from patentability forcefully and demand action from the WTO

Notes, Bibliography and References

Notes

* The perspectives in this submission may not necessarily reflect the totality of views of each member of the GHLC. It is intended to further public dialogue and the development of needed options. Peter Beyer, as current staff at WHO, has recused himself from this submission. Frederick Abbott, co-chair of the GHLC, is a member of the Expert Advisory Group. For the Members of the Committee, seehttp://www.ila-hq.org/en/committees/index.cfm/cid/1053/member/1)

** Other important right to health provisions are contained in the Convention on the Elimination of All Forms of Discrimination Against Women (CEDAW), the Convention on the Rights of the Child (CRC and General Comment 15), and the Convention on Persons with Disabilities (CPD).

*** For the purpose of this submission the term Essential Medicines refers to medicines included in the WHO Model List of Essential Medicines and national Essential Medicines Lists.

**** The Committee wishes to stress that the proposals made in this submission should be seen in the context of proposals for reform of the global pharmaceutical R&D framework to ensure financing for R&D while maintaining prices within reach of the people and communities that need access to the innovations (see for example the recommendation of the WHO Consultative Expert Working Group (2012) to start negotiations on a medical R&D agreement (http://www.who.int/phi/implementation/CEWG_Report_5_April_2012.pdf), proposals for creating an intergovernmental consortium for new antibiotics (http://www.globalhealthdynamics.co.uk/wp-content/uploads/2015/06/AMR2015-June-3.pdf) and the proposal “The Framework Convention on Pharmaceutical Innovation and its Related Protocols” submitted to the UNHLP by the GHLC.)

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7 Indian Patents Act 1970.

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12 TRIPS Article 33.

13http://who.int/mediacentre/news/releases/2015/new-essential-medicines-list/en/

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19 Sell, Susan K. "TRIPS-plus free trade agreements and access to medicines." Liverpool law review 28.1 (2007): 41-75.

20 See: http://www.theglobeandmail.com/report-on-business/international-business/us-business/lilly-ramps-up-nafta-fight-over-loss-of-patents/article13223813/ .Accessed January 2016.

21 Article 12(2) (c) and (d) ICESCR.

22 CESCR General Comment 14, para 12.

23 CESCR General Comment 3, para 10; General Comment 14, para 43(d).

24 CESCR General Comment 14, paras 47 and 48.

25 CESCR General Comment 14, para 35.

26Article 2(1) ICESCR; CESCR General Comment 3, paras 13 & 14, General Comment 14, para 39.

27 Article 2(1) ICESCR; CESCR General Comment 3, paras 13 & 14, General Comment 14, para 45.

28 CESCR General Comment 3, paras 13 & 14; General Comment 14, para 39.

29 CESCR General Comment 3, paras 13 & 14; General Comment 14, para 39.

30 CESCR General Comment 14, para 42.

31 Hunt, Paul., Report of the Special Rapporteur on the Right of Everyone to the Enjoyment of the Highest Attainable Standard of Health, Paul Hunt, Annex: Mission to GlaxoSmithKline, UN Doc. No. A/HRC/11/12/Add.2 (2009). Available at http://www.who.int/medicines/areas/human_rights/A_HRC_11_12_Add_2.pdf  . Accessed February 2016.

32 Ruggie report 2011, para 13.

33 Hogerzeil, Hans V., Samson, Melanie., Vidal Casanovas, Jaume., and Rahmani-Ocora, Ladan. "Is Access to Essential Medicines as Part of the Fulfilment of the Right to Health Enforceable through the Courts?" The Lancet 368.9532 (2006): 305-11. Available at http://www.sciencedirect.com/science/article/pii/S0140673606690764

34 Biehl, João, et al. "Between the court and the clinic: lawsuits for medicines and the right to health in Brazil." Health Hum Rights 14.1 (2012): E36-52.

35 See: WHO definition of Essential Medicines, http://www.who.int/medicines/services/essmedicines_def/en/ . Accessed January 2016.

36 For details see: www.medicinespatentpool.org . Accessed February 2016.

37 Frederick M. Abbott, Intellectual Property and Public Health: Meeting the Challenge of Sustainability. The Graduate Institute. Geneva (2011).

38  http://www.who.int/hiv/amds/WHOTCM2005.1_OMS.pdf . Accessed February 2016.

39 Cf. Reichman, J.H., Hasenzahl, C., Non-voluntary Licensing of Patented Inventions Historical Perspective, Legal Framework under TRIPS, and an Overview of the Practice in Canada and the USA. Issues paper number 5; Geneva: UNCTAD-ICTSD Project on IPRs and Sustainable Development. 2003

40 Correa, Carlos María. Integrating public health concerns into patent legislation in developing countries. Geneva: South Centre, 2000. Available: http://apps.who.int/medicinedocs/pdf/h2963e/h2963e.pdf Accessed February 2016.

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Laura Laughlin, Sanofi Pasteur

Name of Lead Author: Laura Laughlin
Organization: Sanofi Pasteur
Country: France

Please note: The following article is an initial work that was subsequently published as Watson and Faron de Goër, "Are good intentions putting the vaccination ecosystem at risk?" Human Vaccines & Immunotherapeutics, 2016.

Abstract

Vaccination prevents five premature deaths every minute and was pivotal in the 49% decrease in the mortality among children younger than 5, between 1990 and 2013. Increasing access, coverage and sustainability of vaccination has the potential to save even more lives. Vaccination is made possible by an interconnected and interdependent ecosystem of vaccine producers, vaccine procurers, vaccination policy makers and implementers, and vaccine purchasers, whether national governments, donor governments or philanthropic donors. The future of vaccination depends on the continued health of this ecosystem and its ability to produce, purchase, deliver, and innovate. However, over recent years the number of vaccine producers that also do significant research and development (R&D) is decreasing. Many of these R&D‐based producers have been forced to cease production of critical vaccines, such as measles‐containing vaccines, yellow fever, and diphtheria‐tetanus‐polio despite global shortages of these vaccines and in many cases only one global WHO pre‐qualified vaccine available to GAVI and UNICEF. Available data shows a vaccination ecosystem that is overly focused on measuring success through vaccine price and that this focus is asymmetrically impacting global vaccines R&D and heritage vaccine production in the North. If the ecosystem is to remain healthy and sustainable and avoid a tragedy of the commons, akin to antibiotics
then we must refocus on the holistic goals laid out in the Global Vaccination Action Plan (GVAP.) Achieving these goals will require a more inclusive oversight that includes market experts and producers and the development and serial collection of a set of metrics that allows the global health community to truly understand and measure the health and impact of vaccination and the health of future innovation in all aspects of vaccines and vaccination.

Submission

Introduction
Vaccination prevents five premature deaths every minute and has been pivotal to the 49% reduction in under‐five mortality between 1990 and 2013 [1]. Increasing access, coverage and sustainability of vaccination has the potential to save even more live [2]. Delivering this potential requires sustainable ability to innovate and to produce, purchase, and deliver vaccines and vaccination. However, the number of global vaccine producers that are also conducting significant research and development (R&D) has continuously decreased over the last 30 years [3‐5]. In 2002, UNICEF highlighted the fact that between 1998 and 2001, 10 of 14 manufacturers partially or totally stopped production of traditional vaccines and most recently both Baxter and Novartis divested their vaccines divisions [6‐8].Vaccine producers, vaccine purchasers, and philanthropic donors collectively make up the dynamically interconnected and interdependent vaccination ecosystem. We use existing data to consider whether the vaccination ecosystem is healthy and able to adapt to meet global demand for supply and innovation, and whether the most likely evolution of today’s vaccination ecosystem is consistent with the long term goals of the vaccination community. Finally, we suggest ways that the stewardship of the vaccination ecosystem can be more effectively guided, measured, sustained and improved for the present and the future.

The vaccination ecosystem
In 1998 there were14 R&D‐based vaccine producers, today there are just 4 remaining [6]. This contraction has resulted from the inability of producers to absorb the combined cost of the high volumes and low prices demanded by global vaccination programs, the increasing pre‐clinical, clinical, pharmaceutical and quality standards expected by regulators and producers and evolving technology of vaccine production technology [12]. These pressures, and the dramatic industry contraction, have been documented by UNICEF as have the resulting shortages of diphtheria, tetanus, and pertussis (DTP), Bacillus Calmette‐Guérin (BCG) vaccine against tuberculosis and oral polio vaccine (OPV) [6,13]. Many of these shortages persist today [14].

On the positive side, advances in biotechnology in the 1980s and 90s saw the development and licensure of a new generation of innovative vaccines against H. influenza type B (Hib), N. meningitides, S. pneumoniae, human papillomavirus (HPV), rotavirus, zoster, hepatitis B (HepB), as well as new combination vaccines [15,16]. The creation of GAVI, the Vaccine Alliance, in 2000 created a mechanism to address the low income market failure through donor‐funded purchase of vaccines and implementation support in the poorest countries. Today GAVI is the world’s largest vaccine procurer by volume, procuring for 58% of the global birth cohort i.e., ~75 million children and spent US$ 1.7 Billion in 2015 on vaccines [17]. GAVI is funded by philanthropic donations, most notably from BMGF and national donors [18–20]. The GAVI‐led volume of demand and demand certainty, theoretically addresses the pre‐GAVI market‐failure by giving producers the confidence to invest in producing higher volumes at lower costs and to produce better adapted vaccines such as pentavalent DTP‐Hib‐HepB in place of [21]. It therefore accelerates introduction of the innovations of the 1980s and 90s such as pneumococcal conjugate vaccine (PCV), rotavirus and HPV. GAVI therefore focus their market‐shaping on increasing demand and demand certainty in return for reduced vaccine prices. This may address the vaccination gap for which price was the barrier to access. However, one in five of the world’s children still does not receive even the minimum EPI vaccines, including GAVI‐funded, cents‐a‐dose vaccines such as DTP and OPV [22]. For these 20 million children and these vaccines, the barrier is not price but the health
and vaccination systems, as well as political will, fiscal space, awareness, acceptance, education, and physical access. In this situation, low price focused market‐shaping is not solving the underlying problem and risks creating unintended negative consequences because of its asymmetrical impact on the two different types of vaccine producers.

The vaccination ecosystem is supplied by two types of producers: those that produce and significantly self‐ reinvest in research and development (R&D), and those that focus almost entirely on production. R&D‐based producers manufacture vaccines that they have developed. They self‐invest in the R&D of new and improved vaccines. They are headquartered in high income countries and supply globally to almost all private and public markets. Their capital and operating costs are high due to their location, R&D investment, and the diversity and level of the regulatory, quality, and commercial demands of supplying all markets [22]. Non‐research producers manufacture vaccines that were usually developed by others. They invest little in R&D infrastructure and know‐how, and their primary costs are production related [22]. Developments such as MenAfrivac® are partly or fully subsidized [23]. They are based in lower‐middle and middle income countries, sell to domestic procurers or UNICEF/GAVI/PAHO, and focus on high volume and low price [22]. A 2002 GAVI board report confirmed that these producers had significantly enhanced their scale and product breadth but had little experience in developing new products, and had not invested in the R&D infrastructure and know‐how possessed by US and European manufacturers [24]. In 2012 non‐research producers supplied around half of the total volume procured by UNICEF [24]. 

There are also two main types of procurers. Self‐procurers are primarily high and middle-income countries that autonomously define and implement vaccination policy. The higher prices they pay make tiered pricing possible for lower income countries [26‐28]. The pooled procurer GAVI purchases vaccines through UNICEF for countries with gross national income (GNI) per capita of below USD 1570 [29]. Their vaccination policy and regulatory and quality standards are taken primarily from WHO [30‐32]. PAHO countries finance and manage their own vaccination programs but may pool procure through the PAHO revolving fund [33]. Despite relatively high GNI/capita they controversially seek to access the lowest vaccine prices by reference pricing through the Lowest Price Clause (LPC) mechanism [22,28,34]. Since 2001, GAVI and R&D‐based producers have agreed tiered prices for rotavirus, HPV and PCV that are less than one tenth of non‐GAVI prices (Figure 2) [15,36‐40]. The weighted average price (WAP) of the DTP‐based pentavalent vaccine has decreased by 20‐65%, driven by a combination of more suppliers and a shift from single dose presentations to less‐expensive multidose presentations [39]. The prices of MMR (‐45% to ‐59%) and HepB (‐46% to ‐48%) were reduced by about half. Today, however, MMR is supplied by a sole producer and price increased in 2014 by 10%. HepB vaccine is now supplied by two producers, compared to six prior to 2010. The price of the other UNICEF procured vaccines has remained unchanged or has increased. Of concern is the fact that since 2001, the number of vaccines manufactured by a single producer has tripled, from two to six (Table 1), and in 2014 six of eight vaccines
procured by GAVI are in limited or very limited supply [14,41].

Vaccine research and development
Vaccination R&D is long (over 10 years), risky, and expensive, often costing in excess of $1 billion [42,43]. Many vaccines are over 70 years old and require significant periodic reinvestment, as well as continuous reinvestment at a lower level, to meet the evolving technical, regulatory, and quality requirements, and changing market demands. Reinvestment is either self‐generated (i.e., income, or sales minus costs) or externally subsidized. However the two producer species have different sales and costs, and therefore different income profiles.

The largest non‐research producer re‐invests 3.1% of sales in R&D compared to 13.9% for an R&D producer such as Sanofi Pasteur, and whilst a 2005 study found that the emerging manufacturers spent 4‐14% of sales on R&D, the maximum was $6M compared to around
$500M per year by each of the four global R&D‐based producers (GSK, Merck, Pfizer, and Sanofi Pasteur) [44‐49].

Non‐research producers have fewer purchaser and supply points, and fewer product versions with fewer regulatory and release obligations. Manufacturing facilities, labour, and other production costs are also lower in lower income markets. Manufacturing facilities in developed countries cost $200 to $400 million compared to less than $100 million in India [21]. Consequently operating and production costs represent 43% of a non‐research producer’s income, compared with 64% for a typical R&D‐based producer, and the resulting net profit margin can be twice as high for the former (49.5%) compared to the latter (24.5%) [48‐50]. As a consequence of this financial asymmetry, non‐research producers can remain profitable at a price where an R&D‐based producer cannot. It is this loss of profitability that has forced some R&D producers to stop producing some vaccines. For example Crucell withdrew from yellow
fever vaccine, Sanofi Pasteur from measles‐containing vaccines and DTP vaccine, as did CSL limited. This is despite the global supply shortages of all three [21,22,28].

The health and future of the vaccination ecosystem.
Today, the vaccination ecosystem is shaped by a focus of the world’s largest vaccine procurer, GAVI, on the short term, static efficiency goal of increasing demand and lowering prices across all producers. The GAVI price is also increasingly becoming the reference of LMICs and PAHO, revolving fund countries. Focus on price alone does not take explicit account of the asymmetric cost base of the two different producer species that supply them. As prices fall, the profit margins for the same vaccines sold at the same prices become proportionately smaller for the R&D producers compared to the non‐R&D producers. For a given vaccine, when the threshold of acceptable margin is crossed for a producer or when significant reinvestment is required, the R&D‐based producers’ higher cost‐base and break‐even point force them inevitably to exit the market first (figure 2). In other words, R&D producers are more sensitive to price pressure. As producers withdraw from the market there are increasing oligopolies and monopolies of supply. Since scaling up vaccine production takes so much time and investment this inevitably leads to supply shortages. If these shortages are not rapidly corrected, then the impact of demand exceeding supply will cause prices to rise and defeat the initial objectives of GAVI. This is currently happening with DTP, yellow fever and measles‐containing vaccines whose prices have risen 200%, 530% and 25%–150%, respectively, since GAVI's birth in 2001 [21,22,28].

At least as concerning is the potential impact on vaccines R&D in terms of volume of work and targeted diseases. R&D‐based producers rely on R&D to generate higher value vaccines that fund further R&D and tiered pricing, keeping them profitable and competitive, despite higher costs [51‐53]. Lowering prices reduces the incentive to invest in R&D and increases the risk of doing so. Continuous price reductions therefore reduce the overall attractiveness of R&D, especially R&D for lower margin products and markets. This will mean less R&D for GAVI countries and re‐concentration of R&D in the North for the North, leaving donors/philanthropy to take on responsibility for all R&D for the South. Many of the GAVI donor countries (Australia, Canada, Germany, European Commission, France, Italy, Netherlands, Norway, Spain, USA, and UK) are also home to the sites of the few remaining R&D‐based vaccine producers. The irony is that their donations and acceptance of price reduction as a primary goal, may be resulting in the loss of their domestic vaccines R&D capability and capacity. This begs the question of how comfortable the donor countries are that their donations could eventually make them reliant on middle and low income country producers for vaccines such as MMR vaccines in case of supply problems or outbreaks.

In a continuing price‐driven static‐efficiency scenario, the R&D‐based producers would be expected to need to consolidate in order to survive through economies of scale. The absorption of Novartis vaccines by GSK in 2015, leaves only four global R&D‐based producers. Of these four, only two produce HPV, MenB and rotavirus, and are able to supply significant quantities of pentavalent and hexavalent, acellular pertussis‐containing, combination vaccines, and only three (GSK, Sanofi Pasteur, and Merck) have significant ranges of vaccines. Today only four (GSK, Sanofi Pasteur, Merck and Pfizer) have estimated annual vaccine R&D budgets of over $200 million each [44‐46,48]. With development costs of innovative vaccines able to exceed $1billion, this scenario is concerning.

Switching to dynamic efficiency rather than a static efficiency approach would address many of the unintended and well documented consequences of a race‐to‐the‐bottom on price [54,55]. With dynamic efficiency, metrics shift from price alone to a broader set of metrics that recognize quality, supply reliability, vaccination coverage and future innovation. These metrics are aligned with the goals of a healthy vaccination ecosystem, unlike price. With dynamic efficiency, procurement and pricing could be constructed to recognize and reward R&D, the construction and maintenance of production facilities, and the wages of highly skilled personnel involved in production, quality control, and compliance with regulatory requirements. Such an approach is only possible with clear set of shared goals with which to match the companion metrics. The vision already exists in the form of the WHO Global Vaccine Action Plan (GVAP), however the companion metrics do not exist [56]. We argue that a dynamic efficiency strategy, with market‐shaping, procurement, pricing and metrics aligned with the GVAP goals represents a healthier future for the vaccination ecosystem. Unless we are able to shift to a more holistic impact‐aligned set of ecosystem metrics we are at risk that the current ecosystem is not sustainable. There is a real possibility that changing global health priorities, changing political leadership, donor fatigue, or adverse economic
conditions could cause donations from governments and philanthropists to fall. For examples if Ebola had not been contained or if a new HIV were to emerge. In this scenario, there would be a reversion towards the pre‐GAVI era. The lowest income countries would be forced to either raise income or reduce vaccination, leading to less demand certainty and visibility, and probably lower volume demand. In turn, this would lead to price increases. In the absence of third‐party subsidy behind many technology transfers, such transfers to non‐R&D producers would be less attractive and unsubsidized non‐research producers would probably be less viable. This undesirable scenario highlights the implicit risks of over‐dependence on subsidy. It reminds us why GAVI has a graduation policy, whereby countries raise their financial contribution as their GNI/capita increases. It also emphasizes the need to build an ecosystem that is sustainable, incentive‐based, and driven and measured by holisitic public health objectives and metrics, rather than an ecosystem shaped by the belief that that low price will solve all problems [28,57,58]. In reality focus on price alone will create as many problems as it solves.

Conclusion and Proposal
Philanthropic funding over the last decade or so has been pivotal to efforts to provide access to vaccination in the lowest income countries. Removal of these subsidies would have far reaching negative effects on the entire ecosystem and is neither desirable nor in any way suggested here. However we must ensure that the sustainability of the vaccination ecosystem is not compromised to achieve short term goals, and that the ecosystem does not become over dependent on subsidy. Broadening vaccine manufacturing capability and capacity globally is desirable for the vaccination ecosystem, but this should not be achieved at the cost of lost vaccine production capability and capacity in Europe and North America. Not only would this be undesirable for the ecosystem, it would be ironic given their location in the donor nations. As a metric, price is convenient and attractive for donors and politicians, but does not reflect the complex realities of the vaccination ecosystem or the WHO Global Vaccine Action Plan, which calls for improvement in country ownership, shared responsibility, equity, integration of immunization systems, sustainability and innovation [56]. The recent, unintended adverse consequences of this static efficiency on vaccine supply, price, and number of producers can be viewed as warning signs from within the ecosystem. If market failure akin to that seen in antibiotics is to be avoided, then the true interrelationships and dynamics of the vaccination ecosystem must be recognized and the ecosystem stewarded accordingly [61]. In this regard, we make the following recommendations. Public health policy makers, influencers, funders and financers should be made aware of the dynamics, strengths and weaknesses of the vaccination ecosystem. The vaccination community should be refocused on the shared, short‐ and long‐term goals for the ecosystem that should be aligned and consistent with the GVAP goals. These goals should be achieved through aligned actions, incentives and most importantly the development and implementation of a set of metrics that are planned, enacted, and managed by true cross‐partner collaboration. Global oversight bodies such as the WHO’s SAGE should not be restricted to public health experts alone but should also include representatives from vaccine producers, as well as experts in economics and market dynamics. Market‐shaping, procurement and pricing practices all have their place but to be successful and to avoid unintended consequences they must be aligned with best practice, and coherent with the strategic objectives for the ecosystem. The ecosystem will only remain healthy if it is overseen not only by experts in public health, but also by those that understand the functioning of healthy markets and vaccine research, development and production. This oversight must be accompanied by a set of companion metrics that allow us to track the holistic health and impact of the vaccination ecosystem and avoid the unintended consequences of an obsession with price reduction as the only metric of success. 

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Rujitha Shenoy and Madhuri Anand, Inter University for IPR Studies

Name of Lead Author: Rujitha Shenoy and Madhuri Anand
Organization: Inter University Centre for IPR Studies
Country: India

Abstract

Right to health has become a fundamental right, but access to medicine still remains as unreachable to humankind. In this context Intellectual property, Patents as a factor for non availability/un affordability of the medicine , authors attempt to examine the effectiveness of Section 3(d) of Indian patent Act in preventing patenting of incremental innovations and balancing inventors rights. Whether balance can be attained between inventors rights and access to medicine. Also how far  pre-grant opposition helped in maintaining the quality of patent based on the standards. study will be conducted to find out whether  Section 3(d) could be adopted as a model for maintaining a balance of inventors rights with providing access to medicine for the humanity

Submission

Role of Section 3(d) under Indian Patent Act: Balancing inventors rights and access to medicine

Background of the study

Access to essential medicines - as part of the right to the highest attainable standard of health ("the right to health") is well-founded in international law. The right to health first emerged as a social right in the World Health Organization (WHO) Constitution (1946) and in the Universal Declaration of Human Rights (1948).One of the factor which hinders access to medicine is its high cost due to patent protection. While right to health has emerged as human right the attempt is to examine how Indian patent act balances access to medicine and right of the inventor.

The origin of patent law in India can be traced back to 1853 when we were under the dominion of British rule. The Indian law then was similar to the UK patent Act where product and process patents prevailed without difference on all inventions from different industrial sectors. The 1911 Patent Act made Indian pharmaceutical industries really struggle to thrive in this patent regime. After independence, our policy was to bring up industries, mainly pharmaceutical industries, considering the economic conditions of the country as well as social impact of those industries. Justice Rajagopala Ayyangar committee Report[1] resulted in the revamping of the Indian patent regime. One of the major steps was limiting patent protection of pharmaceutical inventions to processes in the pre-TRIPS era. The Patent Act of 1970, contained an express prohibition dealing with patentability of pharmaceutical products; however, it permitted patents on processes for making pharmaceutical compounds, even though the duration of those patents was shorter than other types of patents.[2] This made India emerge as a globally recognized producer of low-priced generic drugs and leading exporter of medicines.[3]

India’s patent law began to take a different course with its accession to the World Trade Organization and signing of TRIPS Agreement in 1995. Changes were made to the Patent Act to make it TRIPS complaint. The amendment inter alia reintroduced patenting of pharmaceutical products which was excluded by 1970 Act along with product patents. Some of the curative measure adopted by India so as to compact with product patent regime were by tightening the  Section 3(d) in 2005 by incorporating the term ‘which does not result in the enhancement of the known efficacy of that substance to lessen the ill effects of product patent for pharmaceuticals’. The objective of this amendment was to prevent incremental innovations, especially in pharmaceuticals, getting property rights. The intention of the Parliament was to prevent the extension of patent life by ever greening,[4] i.e. trying to extend patent protection by obtaining separate patents on multiple attributes of a single product[5] and to ensure that monopoly privileges are not available for new forms without significant evidence of improvement.

In the much debated case of Novartis AG v. Union of India,[6] the Supreme Court of India finally settled the true import of Section 3(d) of Indian Patent Act. The issue before the court was whether the appellant/Novartis is entitled to get the patent for the beta crystalline form of a chemical compound called Imatinib Mesylate which is a therapeutic drug for chronicmyeloid leukemia and certain kinds of tumours and is marketed under the names Glivec. By applying Section 3(d) the court interpreted the term efficacy as“the test of efficacy would depend upon the function, utility or the purpose of the product under consideration in the case of a medicine that claims to cure a disease, the test of efficacy can only be ‘therapeutic efficacy”.[7] The physico-chemical properties cannot even be taken into account for the purpose of the test of Section 3(d) of the Act, since these properties have nothing to do with therapeutic efficacy. Even increased bioavailability alone may not necessarily lead to an enhancement of therapeutic efficacy.[8] Thus court held that beta crystalline form of Imatinib Mesylate is not patentable.

The objective of the research is to make a study on how the Patent Office of India dealt with the patent application relating to pharmaceutical products in the light of the Supreme Court decision on Novartis case and the interpretation given to the term “efficacy” of Section 3(d). This will include the total number of patent applications that dealt with Section 3(d); the number of applications rejected based on Section 3(d) and the number of patent granted. Attempt will also be made to trace whether the pre-grant oppositions were filed against these applications and in such cases what is the impact in implementing section 3(d) by the Patent Office.

Objectives

1. To study the effectiveness of Section 3(d) in preventing patenting of incremental innovations and balancing inventors rights with providing access to medicine
2. To study the pre-grant oppositions if any, to see how patent offices in India handled such oppositions post Novartis case and the contribution of pre-grant opposition in maintaining the quality of patents based on the standards laid down in Novartis case

Research problem

1. How far has Section 3(d) been effective in preventing the ever greening of patents after the Novartis case?
2. Whether Section 3(d) could be adopted as a model for maintaininga balance of inventors rights with providing access to medicine
3. Whether the pre-grant opposition helped in maintaining the quality of patent based on the standards laid down in Novartis case?

Methodology

Collect all the patents issued or rejected relating to pharmaceutical substances based on Section 3(d) after Novartis case by the Indian Patent Office  and study them to find out how the Patent Office interpreted and implemented Section 3(d). To collect all the materials relating to pre-grant opposition filed in cases relating to patent applications for pharmaceutical substances after Novartis case from patent offices of India and find out their influence in deciding the application of Section 3(d). The countries having similar provisions to pre grant oppositions or identical provisions will be identified to study effectiveness of pre grant oppositions in preventing ever greening of patents and there by providing access to medicine and quality patents on drugs. ( Expenses incurred for collecting data from patent offices in Delhi Chennai Mumbai. Time period One Year for the completion of the project.

Out put

Section 3(d) of Indian Patent Act along with pre grant opposition prevents ever greening of patents and ensures quality of patents on pharmaceutical substances tus ensuring balance of inventors rights and access to medicine.

Bibliography and References

1. Philip cullet: Patent and health relationship between human right and health medicine
2. MD NAIR, TRIPS and access to medicine, JIPR vol.17,july2012
3. THE USE OF FLEXIBILITIES IN TRIPS BY DEVELOPING COUNTRIES: CAN THEY PROMOTE ACCESS TO MEDICINES?Sisule F. Musungu & Cecilia South Centre, 2006
4. INTELLECTUAL PROPERTY RIGHTS AND ACCESS TO MEDICINES   
5. GLOBAL COMMISSION ON HIV AND THE LAW
6. Drug Access, Patents and Global Health: 'Chaffed and Waxed Sufficient' Author(s): Mark Heywood Source: Third World Quarterly, Vol. 23, No. 2, Global Health and Governance: HIV/AIDS (Apr.,2002), pp. 217-231
7. Chan Park, Achal Prabhala and Jonathan Berger -Using Law to Accelerate Treatment Accessin South Africa:  AN ANALYSIS OF PATENT, COMPETITION AND MEDICINES LAW United Nations Development Programme, October 2013
8. Trade Policy and the Politics of Access to Drugs Author(s): Caroline Thomas 
9. Source: Third World Quarterly, Vol. 23, No. 2, Global Health and Governance:     HIV/AIDS (Apr.,2002), pp. 251-264

1. FICC’s position on section 3(d) of Indian Patent AcT

[1] Report on Patent the revisions of the patent laws by Justice N Rajagopala Ayyangar, 1959

[2] Patent Act, 1970 section5 (a)-(b) and section 53

[3] Janice M. Mueller, The Tiger Awakens: The Tumultuous Transformation of India’s Patent System

and the Rise of Indian Pharmaceutical Innovation, 68 U. PITT. L. REV. 491, 514 (2007).

[4] “Evergreening” is a term used to label practices that have developed in certain jurisdictions wherein a trifling change is made to an existing product, and claimed as a new invention.

[5] Novartis v UOI, SCC 2013

[6] SCC 2013

[7] Ibid p.90

[8] Id p.93

Seema Rath and Sunitha Srinivas; Rhodes University

Abstract

TRADE RELATED INTELLECTUAL PROPERTY RIGHTS AND ACCESS TO ESSENTIAL MEDICINES FOR NON-COMMUNICABLE DISEASES WITH A FOCUS ON SOUTH AFRICA

Seema Rath1 and Sunitha Srinivas2

ABSTRACT

The access to essential medicines is accorded vital importance in addressing the problem of communicable diseases and the epidemic rise in non-communicable diseases. Access to affordable essential medicines for chronic diseases is necessaryto eradicate poverty and inequity. However, several policy and implementation incoherencies such as, TRIPS-plus agenda of evergreening and data exclusivity have a negative impact on accessibility of  affordable medicines, which are a major  hindrance to advancing human rights and achieving sustainable development. South Africa, despite being an upper middle income country, faces high levels of poverty and inequality, and low life expectancy. Even though, the Constitutional recognition of Health as a Human Right, and access to affordable essential medicines for all, there is lack of availability of essential medicines for non-communciable diseases in its public facilities. South Africa has a depository patent registration system rather than an examination system, leading to liberal grant of patents. This restricts the entry of innovators and generic manufacturers leading monopoly control. Its medicine prices in the private facilities are one of the most expensive ones in the world. Despite adequate policies in South Africa, like many other LMICs, the gap between policy and practices are expanding. Hence, there is a need to modify national patent laws to facilitate access to essential medicines. By proactively incorporating mechanisms such as, the Medicines Patent Pool, Compulsory Licensing and Access to Medicines Index, it can facilitate increased  accessibility of affordable medicines. Adopting the flexibilities allocated by the World Trade Organisation will enable to achieve the universal goal of healthy lives for all and lead to Global Sustainable Development.

Submission

Eradication of extreme poverty and discrimination is the key to progressive realisation of sustainable development with an empowering impact on the population’s health (UN, 2015). The Constitution of World Health Organization (WHO), the Universal Declaration of Human Rights, the International Covenant on Economic, Social and Cultural Rights (ICESCR) and the Alma-Ata Declaration of 1978 (WHO, 1978) are some of the leading evidence based principles that make it obligatory for Member States to take deliberate and concrete steps for full realization of the Right to Health, with emphasis on vulnerable and marginalized groups (WHO et al., 2012). The realization of right to health gets adversely affected due to high prices of essential medicines and lack of equity in their, and need for out-of-pocket payments by the poor and vulnerable (WHO et al., 2012). Hence the Millennium Development Goals (MDG) 8.E and now the Global Sustainable Development Goal (SDG) 3.8 have continued to focus on achieving universal health coverage, including affordable essential medicines and vaccines for all (UN, 2015). Though, health is constitutionally recognised as a fundamental Human Right in 135 nations, only four national constitutions specifically mention universal access to medicines (Perehudoff et al., 2010). The results of an interim assessment of the implementation of the WTO’s Medium-term strategic plan 2008–2013 to achieve a set of health goals, indicates that, of the 11 strategic objectives, progress achieved was maximum under strategic objective 1 for communicable diseases while the least under strategic objective 3 for non-communicable diseases (WHO, 2011; Mendis et al., 2012).

The present paper analyses access to essential medicines, especially for those related to the treatment of non-communicable diseases (NCDs) in light of the Right to Health and the Trade Related Intellectual Property Rights (TRIPS) of the WTO in Low and Middle Income Countries (LMICs), with a special focus on South Africa. 

The first section reviews the provisions of TRIPS and their impact on access to essential medicines in LMICs. The second section focuses on the access to essential medicines in South Africa in light of IPRs, while the third section highlights future course of action needed in patent laws to make the essential medicines for NCDs both affordable and accessible in LMICs.

TRIPS and Essential Medicines

Many studies have highlighted the inaccessibility to affordable essential medicines in public sector health care facilities especially to poor sections of societies in LMICs (Jung and Kwon, 2015; Mendis et al., 2012; WHO 2010a, 2010b). This forces patients to purchase expensive medicines from the private sector, or forgo treatment (WHO, 2010b). Medicine product patents introduced by the WTO and TRIPS has resulted in monopoly control by the patent holders and delayed entry of  lower-cost generic medicines (Jung and Kwon, 2015; WHO and HAI, 2011) leading to exacerbated poor access to essential medicines in LMICs (Jung and Kwon, 2015; Watal, 2000).

Income inequalities produce highly convex demand curves for essential medicines- a normal situation in many developing countries associated with profit-maximizing strategies (Sean Flynn et al., 2009). Several policy and implementation incoherencies such as TRIPS-plus agenda of evergreening and data exclusivity have a negative impact on advancing human rights and achieving sustainable health outcomes (Quigley, 2015). Institutional leaderships have allowed sustainable policy impact in adopting mechanisms such as Medicines Patent Pool (MPP) that enables building partnerships under creative licensing strategies to  accelerate medical innovation (Krattiger, 2013). Apart from encouraging generic manufacture and the development of new formulations benefiting low-cost medicines to LMIC, the development of poly pills advances sustainable health outcomes (MPP, 2016; UNITAID, 2016).

Non-Communicable Diseases: The rapidly growing NCDs epidemic is a major cause of global morbidity and mortality. NCDs accounted for 68% of global deaths, of which 80% occurred in LMICs, with over 40% of these being premature deaths under the age of 70 years (WHO, 2014). The epidemic is predicted to cause approximately 75% of all global deaths by 2030 (WHO, 2015). NCDs are a great danger to sustainable human development, as they result in an increased dependency ratio due to disability and the loss of labour, exorbitant continuous treatment costs, and, thereby, lead to a vicious circle of poverty among the poor (WHO, 2013). Hence, there is a vital need for access to appropriate medicines for treating  NCDs (Abegunde et al., 2007).The WHO’s Global Action Plan includes a voluntary target of 80% availability and affordability of essential medicines for the prevention and treatment of diabetes, cardiovascular disease, and respiratory diseases, both in public and private health facilities (WHO, 2016).  However, access to medicines and vaccines to prevent and treat NCDs is unacceptably low, globally and, more especially, in LMICs (Abegunde et al., 2007; Hans V. Hogerzeil et al., 2013; WHO and HAI, 2011).Various case studies in LMICs, pertaining to NCDs in general and specific ailments have revealed the lack of availability of essential medicines, especially in public health facilities leading to adverse economic consequences (Beran et al., 2015; Jingi et al., 2014; Katende et al., 2015; Robertson et al., 2015). High Price and variations across countries for essential medicines such as  insulin results in various incoherence issues ultimately leading to deprivation of affordable medicines for poor in LMICs (HAI, 2016).Valuable experiences (Kishore et al., 2011) gathered from thelong sustained HIV AIDS programs can be used to identify the way forward to manage the challenges in treating the NCDs (Hans V. Hogerzeil et al., 2013).

Access to Essential Medicines in South Africa

South Africa, an Upper Middle Income Country with a medium human development index, faces a very high incidence of poverty and income inequality (Table 1). The Constitution of South Africa has included the Right to Health as a Human Right and health objectives of the country guarantee the availability, and the accessibility of essential medicines to all of its citizens (Government of South Africa, 1996). However, its Constitution does not specifically commit to access to essential medicines (WHO, 2010b) but describes access to health care, goods and services in more general terms  (Perehudoff et al., 2010).The National Drug Policy (NDP) for South Africa, 1996 aims to provide equal access to medicines for all through the Essential Drugs Programme (DOH, SA, 2016).

Table 1: Development Indicators of South Africa 

Source: Compiled from data of The World Bank 2015; UNDP 2015

The country faces a double burden of both communicable and non-communicable diseases, leading to low life expectancy (Table 2).

Table 2: Proportional Mortality by Causes in South Africa

Source: World Health Organization, 2014a.

The proportion of non-communicable diseases, though lower than when compared to that in advanced and many developing countries, due to higher death rates on account of communicable diseases, is remarkably high, when consideringabsolute numbers due to NCD deaths (Table 3). To make things worse, the toll of NCDs falls mainly on the productive population.

 Table 3: Age-standardised Death Rate due to NCDs by Type per 100,000 in South Africa (2012) 

Source: World Health Organization, 2014b.

Healthcare delivery in South Africa is characterized by a two-tier system of private and public healthcare providers. Until the process of democratisation and universal franchise, the private healthcare was funded by medical schemes, which covered up to 20% of the country’s population, consisting mostly the white section of the population, while the public sector,struggling with poor conditions, catered to the rest of the population (NDP, 1996). The decreasing life expectancy might have proven a cause for concern for health services, resulting in an increase in per capita health expenditure (Table 4) and leading to a nearly twofold increase in per capita health expenditure between 2000 and 2005. This has resulted in a slow increase in life expectancy. The share of the public sector has also been increasing since 2005, although the private sector still makes a higher contribution. This clearly highlights the need for efforts to increase the accessibility of healthcare in a society with a wide income inequality,and high levels of poverty. 

TABLE 4: HEALTH EXPENDITURE AND LIFE EXPECTANCY IN SOUTH AFRICA 

Source: WHO data base

Medicine prices: Even though fast escalation of the prices of medicines is a global phenomenon, private sector medicine prices in South Africa are among the highest in the world. Considering this, the Government of South Africa has developed a National Drug Policy, consisting of the development of an essential drugs programme for public sector primary healthcare facilities (HST). Based on the primary healthcare concept of universal access to healthcare, the essential drugs programme will ensure that drugs for treating the most common ailments are made available, and accessible to the entire population, at an affordable cost to both the government and to consumers (HST).

The economic objective of the National Drug Policy was to lower the cost of medicines in both the private and public sectors, and to promote the cost-effectiveness and the rational use of medicines (NDP for SA). The weak Rand has affected importers of finished medicines and domestic manufacturers using imported raw ingredients by pushing up the cost of production, and thus reducing profit margins. To mitigate the increase in cost, the Health Department of South Africa is planning to allow pharmaceutical companies an additional price increase. However, the step of offering relief to drug companies under margin pressure will adversely affect medical schemes and consumers with further rises in medicine prices. Medicine prices in the private sector are tightly regulated by the Health Department, usually only allowing a one-time annual price increase, based on a weighted formula that includes the consumer price index (70%) and the exchange rate (30%) (Bdlive, 2016). Even then, the prices of medicines in South Africa are on par with some of the highest in the world, making treatments unaffordable to the majority of people, due to limited know-how and a lack of manufacturing capacity by local producers (MSF Access Campaign, 2013). Although the South African medicine pricing system is based on a single exit price, which is in turn based on the manufacturer price decided by the Department of Health, the access to essential medicines for the average South African is limited. It has been observed that some South African based patented medicines, like the Cancer drug Imatinib, fix a higher price in South Africa compared to their pricing in other countries (TAC, MSF and Research and Information System, 2013).

Patent Rights in South Africa

Activist communities believe that patents are barriers to the accessibility to affordable medicines in many developing countries, while the pharmaceutical industry argues that theyare necessary to assure future research, development, and the commercial viability of the industry (Attaran A, 2013). The South African Patents Office operates a formal or depository patent registration system, which is one of the cheapest systems in the world (Pouris and Pouris, 2011). In South Africa, highest proportion of patents applications were granted patents followed by Russia, while the number granted was very low in India, Brazil and Chinaamong BRICS countries in 2011 (Table 5). However, in absolute numbers, China granted the most patents, followed by Russia. All of the BRICS countries follow examination system, with the exception of South Africa (Yu-Fang Wen and Thapi Matsaneng, 2014).

Table 5: Patent applications and grants in BRICS members’ Patent Offices, 2011

Source: WIPO: World Intellectual Property Indicators 2012

In South Africa, the residents’ patent applications and grants formed only around 10% of the total (Table 6).  As the South African patent system does not investigate the merits of each patent based on experiment, multiple patents for a single medicine could easily be granted (TAC, MSF and Research and Information System, 2013) for a 20 year period, and, furthermore, if a secondary patent or follow-up patents (“ever-greening”) are granted, competition would be restricted (European Medicines Association, 2008). The depository patent system probably allows for unjustifiable patents that might restrict competition by discouraging research and development by competitors, and would restrict access by generic manufactures. Substantive patent examination systems could eliminatelow-quality patents that protect inventions of limited novelty, or from providing overly broad protection.

Table 6: Patent applications and grants by the South African Patent Office, 2011

Source: WIPO: World Intellectual Property Indicators 2012 

Competition Policy:Competition policy plays an important role in ensuring that there is sufficient competition amongst manufacturers in making pharmaceuticals more accessible and affordable which can be achieved by competition between manufacturers of different originator medicines and/or competition between originator and generic manufacturers (Yu-Fang Wen and ThapiMatsaneng 2014).

Patent Pool: A pill with a combination of multiple medicines will help treating patients under scarcity of resources. However, this can be obstructed due to patents on individual medicines. The Medicines Patent Pool is suggested as a solution to this problem, and is expected to stimulate competition. This can reduce the uncertainty for generics companies in obtaining the rightsto produce a particular medicine from several patent holders, and can be beneficial to all stakeholdersbymaking these medicines accessible in developing countries (UNITAID).

One of the main arguments put forward by industry with respect to the need for strict protection of IPRs is the high cost of R&D for new medical products. However, it has been observed that expenses incurred on pharmaceutical R&D by the private sector formed less than 8 per cent of global yearly medicine (and other medical tools) sales in 2010 (Love, 2011). American pharmaceutical manufacturers spent almost double their R&D expenses on marketing (Gagnon & Lexchin 2008), and generally take home more in profit than they spend on R&D annually (Tomlinson & Rutter 2014). R&D expenses are not solely borne by pharmaceutical companies, as they are also financed through public funds generated from tax contributions by the general public and other sources (Røttingen, 2013). In South Africa, the Government was the chief funder, contributing 44.4% of the total R&D expensesduring 2009-10 (DST, 2013).

Corporate Social Responsibility:The corporate sector has a responsibility towards the general public,in addition to its responsibility to earn a profit for its shareholders. However, the profit-oriented corporate sector turns a blind eye towards this responsibility to the consumers and general public. This can be clearly observed in the statement of the CEO of Bayer, announcingthat its cancer drug was not developed for poor patients in India, but “for western patients who can afford it,” in response to India’s issuance of a compulsory licence on Sorafenib, allowing generic manufacturing of the medicine in the country (Gokhale, 2014). This medicine, patented in South Africa, is not available to patients in the public sector of the country due to its high price, indicating that development in the pharmaceutical industry is predominantly influenced by the market, rather than the health needs of society ((Tomlinson & Rutter, 2014 ).In South Africa, like in many other developing countries, there is little evidence to support the claim of the industry that the adoption of public health safeguards would weaken the development of future medicines.Hence, campaigns like ‘Fix the Patent Laws’ advocate for a more rational patent regime by considering health, developmental, social, and economic needs of the country, along with relevant evidence, rather than a purely capitalist ideology (Tomlinson & Rutter, 2014).

Draft New Intellectual Property (IP) Policy of South Africa: The draft New Intellectual Property (IP) Policy of South Africarecommendsanamendment of legislation to incorporate the Doha Declaration “flexibilities” and incentive schemes in the areas of IP to achieve developmental goals of poverty alleviation and health.It argues for the necessityof applying competition law to patent lawsunder over-concentration, dominance, or abuse by IP holders. It recommends the use of compulsory licences, and parallel importation,for making medicines affordable, and balancing trade withhealth interests in patent protection. Considering the resource constraintsin the country, it recommends a combination of the depository and examination systems for the registration of patents.

India, while obliging to recognise pharmaceutical product patents in terms of the TRIPs, incorporated a number of important flexibilities, such as compulsory licencing, Parallel Imports, the Bolar Exception in its Patents (Amendment) Act 2005, in order to facilitate access to affordable medicines (Health Review). It has utilised section 3(d) of its Patents Act,which relates to higher standards for patentability, to deny Novartis a patent on the anti-leukaemia drug Imatinib (sold as Glivec). It granted a compulsory licence for a generic version of Bayer’s anti-cancer medicine Sorafenib (sold as Nexavar), on the basis that the local generic manufacturer Natco Pharma was able to supply the drug at 3% of Bayer’s price, which was exorbitant (WIPO 2014). These indicate how developing countries can utilise TRIPs provisions to make essential medicines affordable to their populations.

Way forward

Using SDG 3 as a pivotal point, it is essential to drive the process of promoting affordability of medicines for NCDs, by using a public health approach and by utilizing the flexibilities of TRIPs. The short term gains of the corporate sector act as a hindrance to achieving the universal goal of a healthy life for all and of sustainable development. The WTO, which advocates for free trade, and for the elimination of restrictions and monopoly power, requires a review of TRIPs in light of the broader goals of health, to facilitate sustainable development globally. In the era of globalisation, developed member states of WTO should place global human interests ahead of the financial interests of their corporate sectors.

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Vanina Laurent-Ledru, Sanofi Pasteur

Name of Lead Author: Vanina Laurent-Ledru
Organization: Sanofi Pasteur
Country: France

Abstract

In the recent past, innovation in vaccines has been driven by the medical needs of markets that can afford the launch prices necessary to fund and incentivize innovation and production scale up. As a result, vaccines are launched first in developed countries at a small volume and competitive price, before being made available 8 to 10 years later in low and middle income countries (LMICs) at a reduced price. In this conventional model, access in poorer countries tends to be delayed and diseases endemic to these countries only are often neglected. Since the traditional vaccine introduction model does not allow LMICs´ timely access to innovative vaccines, alternative solutions and models are needed. Dengue fever, for which half the world is at risk, but which is endemic mainly in LMICs, provided an opportunity for Sanofi to flip the access model. Sanofi is accelerating access to its dengue vaccine by ensuring priority access to this innovation first in endemic countries where it can have the greatest impact on global dengue burden. A successful launch of the dengue vaccine may chart a new course for private sector investment in LMICs, demonstrating an attractive business model for vaccine manufacturers. It may also promote continued investment in healthcare innovations for LMICs that address their specific medical needs while contributing to development of in-country infrastructure, skills and capacity for managing infectious diseases.

Submission

Communicable diseases such as malaria, leishmaniasis, Chagas disease, tuberculosis, dengue fever, and African trypanosomiasis and more recently Zika extract a heavy toll in lower income countries. Zika´s spread to more than twenty countries mainly in tropical and sub-tropical regions and the anxiety it has fueled among the general public has reopened the debate on the development of new vaccines for diseases affecting mostly low (LICs) and middle income countries (MICs). In fact, 26 years after the Global Forum for Health Research warned against the “10/90 gap” (referring to the Commission on Health Research for Development´s finding that less than 10% of the world’s research & development (R&D) was spent on diseases affecting developing countries where 90% of all preventable deaths worldwide occurred), the gap very much remains.1-2

In the recent past, innovation in vaccines has been driven by the medical needs of markets that can afford the launch prices necessary to fund and incentivize innovation and production scale up. As a result, vaccines are launched first in developed countries at a small volume and competitive price, before being made available 8 to 10 years later in low and middle income countries (LMICs) at a reduced price.3 In this conventional model, access in poorer countries tends to be delayed and diseases endemic to these countries only are often neglected.

This imbalance in disease burden between developed and LMICs raises the following questions: How can we secure LMICs´ timely access to new vaccines at high volume and acceptable cost? How can we encourage manufacturers to invest in R&D and in health solutions tailored to LMICs´ specific needs, in accordance with SDG3?

Since the traditional vaccine introduction model does not favor LMICs´ timely access to innovative vaccines (I), a new more business model, where an innovative vaccine is introduced first in LMICs, is being explored (II).

I. The traditional vaccine introduction model does not allow LMICs´ timely access to innovative vaccines

In the traditional vaccine introduction model, a vaccine manufacturer releases a new vaccine to wealthier countries first. These countries get priority access since they are able to pay a price that enables the producer to continue investing in innovation as well as in increased production volumes. This increased production volume will allow access for lower income countries at a reduced cost, but several years later as it requires 3-5 years and $200-400 million to build a new production facility. This model has been viewed as essential to allow continued investment in innovation and to increasing production volumes.

The combination of this model and the arrival of a significant number of innovative new vaccines in the 90s and 2000s, led to an important gap between vaccines available to developed countries and those available to developing countries, in particular for vaccines such as hepatitis B, Haemophilus influenza type b (Hib), HPV, rotavirus, PCV, influenza etc.4  

Vaccines have proven to be one of the most cost-effective and inexpensive tools for improving health.5 They therefore represent a crucial investment for LMICs whose timely access to this decisive medical intervention is essential.  LMICs´ delayed access to innovative vaccines comes with a cost: medical care cost associated with the disease, outbreak control cost, loss of revenue from tourism, cost of lost productivity etc. while vaccination provides high returns on investment.5 As emphasized by Bloom et al, “Immunization provides a large return on a small investment—higher than most other health interventions” (Bloom et al. 2005). In 2005 for example, a study estimated that a GAVI immunization program´s return on investment was 12% in 2005, reaching 18% in 2020.5

When considering investments, private firms evaluate the market potential: the cost and risks associated with investments and the return to be generated by future sales.6 LMICs tend to be viewed as more unpredictable and less likely to provide the returns necessary to fund innovation than higher income countries. Batson has described how developing markets have been perceived as characterized by inaccurate demand forecasts, constrained and unpredictable government budgets, downward pressure on price and slow market penetration.6 This situation has made it challenging for shareholder-held vaccine manufacturers to address LMICs´ specific needs; launching a vaccine first in wealthier countries allows them on the other hand to pay for innovation and thus to provide later access to LMICs. Despite delayed access, this appeared as a sustainable model to fund necessary innovation and introduce innovative vaccines.

The incentives inherent to the classical vaccine introduction model therefore partly explain the lack of innovative solutions for many infectious diseases specific to LMICs. Acknowledging this situation, global public health institutions and the pharmaceutical industry have come up with solutions based on “push” mechanisms that lower the cost of producing new vaccines and “pull” mechanisms that increase the market for them.7 Several promising and innovative approaches such as Public-Private Partnerships (PPPs) or Advance Market Commitments (AMCs) have been explored to increase incentives to develop new vaccines for LMICs.

Public-Private Partnerships (PPPs) for new vaccines

Covering a wide range of ventures and involving a variety of arrangements, Public Private Partnerships can be described as agreements between government(s), non-profit organizations and one or more private partners which objective is to accelerate vaccine development so as to meet the specific health needs of developing countries. The Bill and Melinda Gates Foundation (BMGF) and the Rockefeller Foundation have been catalysts in the development of PPPs such as Medicines for Malaria or the International AIDS Vaccine Initiative; other well-known PPPs include the TB Alliance and the Meningitis Vaccine Project.8 According to the World Health Summit, PDPs now manage two-thirds of the identified drug development projects for neglected diseases.9

GAVI and the Global Fund were born as PPPs and are now playing a key role in giving access to new vaccines to populations in developing countries. GAVI in particular is bringing together UN agencies, governments, civil society and the private sector to increase equitable use of vaccines in poorer countries.10

Advance Market Commitments (AMCs)

The Advance Market Commitment (AMC) model is a “pull” mechanism devised to stimulate R&D on vaccines for developing countries while guaranteeing a subsidized market for the resulting product.  Under this scheme, donors or governments make binding commitment to pay a specified price for a predetermined number of doses of the vaccine to a vaccine manufacturer so as to incentivize the manufacturer to develop vaccines for neglected diseases. Though “well-designed AMCs could play a role in mid-stage development, they are unlikely to be a practical way to drive R&D for challenging early-stage vaccines that face substantial scientific obstacles” (Keith et al. 2013).11

A handful of emerging countries –India, Brazil, China in particular- are also becoming leaders in the manufacturing of vaccines produced in high volumes for the South.12-13 Emerging suppliers, which include state-owned firms as well as privately-owned manufacturers, provide 86% of traditional vaccines procured at global level.14 These emerging suppliers tend however to manufacture mature and off-patent vaccines which have been available for decades, leveraging cost advantages to produce high volumes at low prices, rather than truly focusing on innovation. They lag behind multinational firms when it comes to technology and know-how, and while “many are quite proficient at scaling up manufacturing processes for mass production (…) they are still quite weak in earlier stages of R&D” (Wilson 2010).15 New generation vaccines thus continue to be produced by a limited number of multinational firms.

Despite above-mentioned positive developments (PPPs, AMCs, key role played by GAVI), resources for developing new vaccines targeting neglected tropical diseases are still comparatively scarce, and are not sufficient to meet these countries´ needs.

It is also important to underline that vaccination entails much more than just selling a product – in this case a vaccine. Vaccination requires the set-up of an entire ecosystem allowing for the effective vaccine implementation and delivery (eg trained health workers, adequate transportation systems, sufficient storage facilities, efficient cold chain system etc).

This raises the question whether it would be possible to develop a health solution designed for LMICs without seeking donor support. In other words, can a vaccine solution for endemic countries be designed while maintaining R&D incentives for the vaccine industry? There is a need today for a new vaccine introduction model allowing endemic populations to benefit from a timely and sustainable access to innovative vaccines tailored to their specific health needs. 

II. Flipping the traditional introduction paradigm with the dengue vaccine

Sanofi has decided to rise to this challenge and to flip the traditional vaccine introduction model with its dengue vaccine.

Dengue is a serious and complex disease which mainly affects low and middle income sub-tropical and tropical countries and which weighs heavily on affected countries’ health systems and economies. The incidence of dengue has increased 30-fold over the last 50 years, but the true magnitude of the disease burden is highly underestimated.16

The Sanofi dengue vaccine—a live, attenuated, tetravalent vaccine—is the only vaccine that has shown evidence of clinical efficacy against dengue in clinical studies and that has been licensed in four countries as of February 18th 2016 (Mexico, the Philippines, Brazil and in El Salvador).17 Based on dengue´s epidemiology, Sanofi has decided to adopt a novel and bold approach to address the challenges posed by the disease and to focus on countries which need it the most.

Priority given to endemic countries where the need it the greatest and to the public sector

For the first time, an innovative vaccine will have its initial introduction in LMICs where the need is the greatest. In fact, Sanofi committed to flipping the access model with the dengue vaccine by ensuring priority access to this innovation first in endemic countries where it can have the greatest impact on global dengue burden.

Sanofi also committed to focusing on public sector introduction in order to ensure a broad access from registration on, and so as to achieve the largest possible impact on disease through large-scale vaccination campaigns. To do this, the company is valuing the vaccine in a way that balances the cost of innovation against affordability in these LMICs.

An early engagement in the R&D and industrial capacity of a dengue vaccine

The company engaged in an ambitious R&D and industrial strategy, long before the dengue vaccine launch. Indeed Sanofi recognized the scale of the dengue problem at its early stages twenty years ago, and started building public health collaborations as well as industrial resources essential to the dengue vaccine´s development and introduction. Considering dengue was a public health emergency, the company made a bold and unusual decision from the start: it chose to develop the vaccine, set-up the industrial capacity and prepare market launch all in parallel, rather than as a sequence as it is usually done.18

Sanofi committed considerable resources to dengue, investing in R&D and industrial capacity. This included a €350 million upfront investment in dedicated, state-of-the-art, high-quality production facilities.19 With a dedicated production plan in Neuville, France, the company has started producing around 100 million doses per year as of 2016, so as to supply one billion doses over 10 years. This early – and at risk- engagement allows Sanofi to have doses available at the time of licenses, and thus to avoid a time lag between license and implementation.

Paving the way for the introduction of future vaccines while creating social value

A successful launch of the candidate dengue vaccine would demonstrate an attractive business model for private companies and promote continued investment in health solutions for LMICs. Dengue could serve as a model for introducing newer vaccines that will also require large-scale vaccination programs. The wider implications of this novel access approach are that emerging markets can begin to drive sustainable private investment in healthcare innovations that address their specific unmet medical needs while building in-country skills and capacity.

In fact, in endemic countries where the clinical trials took place (40,000 individuals enrolled in 15 countries), Sanofi also built local collaborations, empowered local healthcare providers with dengue and vaccine knowledge, and provided upgraded healthcare facilities as well as education on dengue prevention to communities at risk.

It is important to highlight that the “flipping the model” approach also comes with challenges, associated in particular with the lower maturity of LMICs versus developed countries in terms of regulatory capacity, epidemiological surveillance or economic evaluation. These weaknesses need to be compensated by increased collaboration and support, as they could potentially hinder the successful implementation of the dengue vaccine. In this new business model, it has been essential for Sanofi to go beyond the traditional vaccine manufacturing role and to act as a fully-fledged public health partner, working with National Regulatory Authorities, Ministries of Health and the World Health Organization (WHO) to support partner countries through capacity building and through the mobilization of the global health community in the fight against dengue.

In 2010, the BMGF declared this decade “The Decade of Vaccines”.20 The dengue business model for vaccine development and introduction in LMICs is aiming to make this statement a reality and to bridge the “10/90” gap in accordance with SDG 3. If successful, the dengue vaccine introduction model may chart a new course for private sector investment in LMICs, demonstrating that diseases specific to these countries represent viable commercial opportunities for private industry. Vaccine manufacturers may become more inclined to addressing the unmet medical needs of LMICs as a priority rather than as a secondary issue. On the contrary, if the dengue vaccine introduction fails, this market failure might hinder the development of vaccines targeted at LMICs for the coming years.

Bibliography and References

1.      Commission on Health Research for Development. Health research: essential link to equity in development. New York: Oxford University Press; 1990, 157. Available at: http://www.cohred.org/downloads/open_archive/ComReports_0.pdf

2.      RF Viergever. The mismatch between the health research and development (R&D) that is needed and the R&D that is undertaken: an overview of the problem, the causes, and solutions. Global Health Action. 2013;22450:1-10.

3.      DB Brooks, TA Smith, Don de Savigny, C Lengeler. Implementing new health interventions in developing countries: why do we lose a decade or more? BMC Public Health. 2012;12:683.

4.      J Clemens, L Jodar. Introducing new vaccines into developing countries: obstacles, opportunities, and complexities. Nature Medicine. 2005;11 (Suppl. 4):S12-S15.

5.      DE Bloom, D Canning, M Weston. The Value of Vaccination. World Economics. 2005;6 (3) 15-39.

6.      A Batson. The problems and promise of vaccine markets in developing countries. Health Aff. 2005;24(3):690-3.

7.      R Smith. Vaccines and medicines for the world's poorest: public–private partnerships seem to be essential. Br. Med. J. 2000;320:952–3.

8.      RT Mahoney, A Krattiger, JD Clemens, R Curtiss III. The introduction of new vaccines into developing countries: IV: Global Access Strategies. Vaccine.2007;25(20):4003-11.

9.      World Health Summit. A Call for Action to Strengthen Health Research Capacity in Low and Middle Income Countries. World Health Summit Yearbook 2013.

10.  GAVI. Investing in immunization through the GAVI alliance. The evidence base. 2010. Available at: http://www.gavialliance.org/resources/GAVI_Alliance_Evidence_Base_March_2010.pdf

11.  JA Keith et al. Delivering the promise of the Decade of Vaccines: Opportunities and challenges. Vaccine. 2013;Issue 31:184-193.

12.  CA Gardner, T Acharya, D Yach. Technological And Social Innovation: A Unifying New Paradigm For Global Health. Health Affairs.2007;26(4):1052-1061.

13.  CM Morel, T Acharya, D Broun, A Dangi, C Elias, NK Ganguly, et al. Health innovation networks to help developing countries address neglected diseases. Science. 2005;309 (5733):401–4.

14.  UNICEF. State of the World’s Vaccines: Childhood immunization at record high. 2009. Available at: http://www.unicef.org/immunization/index_51482.html

15.  P Wilson. Giving developing countries the best shot: An overview of vaccines access and R&D. 2010. Campaign for Access to Medicines, Medecins Sans Frontieres. Geneva, Switzerland: Oxfam and Campaign for Access to Essential Medicines. Available at: http://www.msf.org.uk/sites/uk/files/Vaccine_Report_201005111518.pdf,

16.  World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control. 2009. Available at: http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf.

17.  Sanofi Pasteur. Sanofi Pasteur's dengue vaccine candidate successfully completes final landmark phase III clinical efficacy study in Latin America [press release]. Available at: http://www.sanofipasteur.com/en/articles/sanofi-pasteur-s-dengue-vaccine-candidate-successfully-completes-final-landmark-phase-3-clinical-efficacy-study-in-latin-america.aspx.

18.  D Bloom, VK Dangan, V Dessain, E Billaud. SanofiPasteur: The Dengue Vaccine Dilemma. Harvard Business School Case Study. 2014. N9-514-074.

19.  Sanofi Pasteur. Sanofi-aventis builds a new vaccine manufacturing facility in France with an investment of 350 million euros [press release]. Available at: http://www.sanofipasteur.com/en/Documents/PDF/PR/20090512-Sanofi-aventis-builds-a-New-Vaccine-Manufacturing-Facility-in-France-with-an-investment-of-350-million-euros.pdf. Published May 12, 2009.

20.  Bill and Melinda Gates Foundation press release: Bill and Melinda GatesPledge $10 Billion in Call for Decade of Vaccines, January 29, 2010. Available at: at: http://www.gatesfoundation.org/press-releases/Pages/decade-of-vaccineswec-announcement-100129.aspx

Lal Manavado, Norwegian Directorate of Health

Name of Lead Author: Lal Manavado
Organization: Norwegian Directorate of Health
Country: Norway

Abstract

Human rights are meaningful to people, only if they are observed in the society in which they live. Extent to which they are observed in a society, reflects the degree of social harmony there.

Possibility of our living, depends on the possibility of our satisfying four fundamental needs, viz., education, nutrition, health and security in its broadest sense. Possibility of our existence as a species, depends on the possibility of our procreation.

The possibility of our leading a civilised life depends on the possibility of our adequately satisfying certain set of non-material needs like creative and aesthetic enjoyment, entertainment, sports, etc.

Social harmonyis essential to enable the members of a society to adequately meet those six fundamental needs.  Hence, observance of human rights is in everybody’s interest. Its neglect would hinder some from adequately satisfying those needs including health.

As a result, burden of disease of that society would increase, which in turn, would adversely affect its division of labour, reducing the possibility some of its other members may have of satisfying their own needs. This would result in a self-expanding evil circle, where human rights loose theirmeaning to the people.

Enhancing their access to medicines and diagnostic material may help people to satisfy one of their neglected health needs, and may thereby restore theirbelief in human rights to some extent.

Submission

Towards an Enhanced Global Access to Medicines and Diagnostic Material

This submission postulates that while good health in a population promotes the observation of human rights, its ill health exerts the opposite effect by adversely affecting general law enforcement, which is essential for human rights to become an experienceable notion.

Other things being equal, ill health has an adverse impact on most human activities including the development of personal and national resources. Deficiencies in law enforcement and access to the requisite human and material resources are not felicitous  either to innovation, or to the justifiable rights of an inventor or a trader.

Therefore, it would be in everyone’s interest to ascertain how one may accommodate the requirements of trade and patent laws on one hand, and meeting somemedical needs of ill health on the other for our mutual benefit. This submission is an enquiry into a possible means of achieving that objective.

Introduction

Our point of departure is that man must adequately satisfy six fundamental needs, viz., education, nutrition, health, security in its broadest sense, procreation and a set of non-material needs like aesthetic satisfaction, entertainment, etc., in order to continue to exist as a sentient and civilised being.

There is no justifiable way to determine which of the first four needs could be given logical priority, because the failure to satisfy one would inevitably lead to one’s incapacity to satisfy any of the others. Our knowledge of what those needs are, and how we may successfully satisfy them are not givens, and they have to be acquired by education.

Other things being equal, the possibility of satisfying those needs depends on the possibility one has in undertaking some suitable action to do so. The possibility of undertaking such an action depends on having the freedom to do so without hindrance from the other people. When a society embodies this freedom, a social harmony obtains there.

Thus, achieving social harmony is in everybody’s interest. Through a long social evolution, man has developed a system of do’s and don’ts to achieve this objective. Typically, it manifests itself as a system of ethics anchored in a belief system. Now it has grown into the current ethico-legal system which displays certain nominal regional variation.

Now, we need to distinguish between rights and laws. As enforcement of the latter is intended to guarantee the former, we can envision trade laws as a means of guaranteeing innovators’ and traders’ rights, which in turn, are only a sub-set of human rights.

Let us continue with health as our example. Other things being equal, people would be motivated to observe human rights, because it is conducive to their satisfaction of health needs. But should the reverse obtain, the resultant social disharmony will hinder them from achieving that goal. This seems to lead us into a Catch-22 situation.

When historical, political and economic reasons have deprived huge populations the possibility of satisfying their health needs for a long time, it is unreasonable to expect them to observe human rights and strive towards social harmony, for in everyone’s mind, one’s own health has a priority over other people’s rights or well-being.

There is a general agreement on the importance of good health as a major contributor to what enables anyone acquiring the abilities and skills necessary to satisfy one’s fundamental needs. Obviously, their adequate satisfaction is necessary, therefore desirable to all, hence, good health has a universal value.

Data from WHO clearly indicate that the global distribution of good health is very uneven owing to the comparatively high burden of disease borne by the less developed countries, and some of its component diseases like AIDS, Malaria, Tuberculosis, etc., are much less prevalent in affluent countries.

Furthermore, the current economic doctrine has had an adverse impact on people’s eating habits throughout the world. As a result, the so-called NCD’s have become a growing component of the global burden of disease. This seems to represent an exacerbating addition to the already considerable burden of disease observable in less affluent countries.

Other things being equal, this entails that the inhabitants of less developed countries are at a considerable disadvantage with respect to adequately meeting their fundamental needs, or acquiring those abilities and skills necessary to successfully satisfy them.

Meanwhile,  spread of information about human rights and popular political doctrines have raised people’s level of expectations to a comparatively high level. In this environment, their reduced possibility of satisfying their fundamental needs, would increasingly undermine their confidence in rule of law essential for social harmony.

As a consequence, some may react with indifference to rules that might manifest itself in some form of escapism or social lethargy. Response of the others may range frompolitical demagogy to violent anti-social action. Where these predominate, the question of human rights and material progress becomes academic.

Thus, good health seems to be an important factor that imparts a tangible value not only to human rights per se, but also something needed to enhance the social harmony that springs from each member of a social group having the possibility of leading a life of contentment in dignity.  It is their  role in sustaining social harmony that justifies attributing a value to respect for law and human rights.

Meanwhile, lack of an adequate access to health care promotes the evil cycle of ever-growing social deprivation and the associated danger of violent social upheaval. Neither of these can be a part of the ambience where inventions are made and turned into innovations, or human rights are adequately respected.

Researchers, creators and purveyors of medicines and diagnostic materials depend on international sales for their livelihood, As the number of those who have no access to needed health care increases,  the possibility of someone circumventing the justifiable claims of the inventors and innovators and the trade laws will continue to increase.

Production and sale of ‘pirate medicines’ is already a growing problem. However, in spite of their questionable quality,  their sales appear to be lucrative enough to encourage this malpractice, because desperate people will seek whatever means at their disposal to alleviate their sufferings.

To sum up then, inadequate access to medicines and diagnostic material is a hindrance to good health, which in turn adversely affects the possibility of many members of a society satisfying their fundamental needs, which would disrupt its harmony. Its diminution would make human rights, patent and trade laws an irrelevance to the people.

The Problem

The path from undertaking an invention to its practical application is not only expensive, but also requires highly specialised human resources and materials. Most countries with a high burden of disease have neither the financial nor the other resources required to develop and produce the medicines and diagnostic material they need.

Other things being equal, If our respect for human rights is claimed to be global in scope, it implies that we must undertake steps not only to ensure our own respect for those rights an laws, but also initiate actions to enable the deprived billions to experience the desirability of respecting human rights and the rule of law.

Attaining this objective entails helping the deprived to achieve social harmony in their midst. The possibility of doing this, depends on their ability to adequately satisfy their fundamental needs. Their health needs are one of them, which remains inadequately satisfied.

Thus, our problem now is how to enable the deprived to achieve an adequate level of health in a way that takes into account the justifiable claims of those create, develop and sell medicines and diagnostic material. This is not a question of charity or historical guilt, for it benefits all.

The reason is quite simple. Nation states have become increasingly dependent on each other to varying degrees. Violence brought about by desperation can spill across frontiers triggering greater misery. Moreover, it reduces trade  including that in medicines and diagnostic material.

A more serious problem is the unpredictability of pathogen emergence. Nobody can rule out the transformation of currently mild pathogens into virulent ones, or hitherto endemic one becoming a pandemic agent as Ebola and Zika viruses have demonstrated. These events have taken place in areas of relatively high burden of disease and less affluence.

Neither violence nor pathogens are respecters of national frontiers. Transport of people and goods on which all creators, developers and sellers of many kinds of product including medicines and diagnostics depend,  could serve as a vector of disease, and may need to be restricted, which would result in financial loss.

The Criteria a Solution Must Meet

We will call them the criteria of universal adequacy, because they embody the principles on which a solution acceptable to all reasonable people could be based:

1.  It will ensure an adequate reward to those who invent, develop and market medicines and diagnostic material.

2.  It will make medicines and diagnostic material accessible/available to the maximum possible number of those who need them but are unable to afford them.

3.  It will protect one’s justifiable right to intellectual property and patient’s right to product or service of adequate quality, and it will strive to uphold justifiable trade laws.

A Possible Means to the Desired End

Apart from the obvious, i.e., seeking the best means of increasing the global access to medicines and diagnostic material needed, it would be useful to prevent increasing the need for them. This latter requires an effective parallel undertaking to expand national endeavours in prevention.

To improve access to affordable medicines and diagnostic material one may resort to two distinct means, viz., internal and external structural and functional efficiency. We will begin with the internal or the national means.

Irrespective of the political colouration of a government, its implemented policies would have a significant effect on national health, and by implication people’s access to medicines, vaccines and diagnostic material. Funds available for their local production or procurement depend on the degree of congruence among relevant policies, and adequacy of their implementation.

A congruent set of policies can be envisionedas a hierarchical network of them, where those above can logically subsume some of those below them. At their top, stands the intent to enable all the citizens to adequately satisfy their fundamental needs including health.

Since it is unjustifiable to give priority to any one of the fundamental needs, policy on health should be given the same priority as the others. Next, policy makers should identify the policy areas where they overlap health. For instance, health consequences of dietary imbalance are well-known.

Moreover, the role environment plays in making agriculture possible on earth, and in buffering extremes of climate are well established. Likewise, appropriate education is vital to better national health. This analysis can be fruitfully continued to map the important policy areas where their congruence with health policy  would enable us to achieve much even with limited resources. This requires high analytic and synthetic abilities.

An example of policy incongruence relative to health would be a trade policy that permits import/production/sale of inappropriate industrial food and drink known to promote dietary imbalance. This is a serious problem in affluent countries, and thanks to the dictates of ‘free trade agreements’, its ill effects are already visible in poor countries.

The next step is policy implementation. It requires a good deal of technical and administrative competence, whose global distribution appears to be somewhat thin. Now, we may justifiably demand a similar policy congruence and implementation competence from the regional and global institutions concerned with health.

At a minimum, we can begin by looking at the health implications of current GATT without succumbing to the temptation to achieve economic growth at the expense of national health. Other areas that require urgent scrutiny include pollution, disposal of dangerous waste, Law of the Sea, and environmental degradation.

Even after achieving policy congruence with respect to health and an adequate policy implementation, the first principle may seem to offer insurmountable difficulties, because many of those who need medicines and diagnostic material cannot pay what inventors, developers and purveyors of those items collectively consider to be sufficient.

I think it would be worthwhile to establish an impartial international technical panel whose brief would be to ascertain a fair price for most needed medicines and diagnostics. Their expertise should include Pharmacology, needs of surgical and clinical practice, epidemiology, laboratory diagnosis, finance, business practice, and the relevant law.

If international consensus on the decisions of such a panel on prices is obtainable, it would be comparatively easy to proceed.  One wonders whether the UN might be induced to procure political support essential to establish such a panel, and whether it is possible to induce pharmaceutical industry to be guided by its decision.

True, introduction of a new medicine or a diagnostic method is a very expensive undertaking. However, there are many established medicines and diagnostic methods, whose present cost does not always seem to be justifiable. Moreover, their potential increased sales may warrant considerably lower prices.

As an adjunctive means, I strongly advocate a technically and legally unambiguous definition of ‘generic’ medicines and diagnostic material. As sale of such products may already have amply repaid those who made their sale possible, it would be justifiable to display here some bias towards the health of the needy.

Now, I would like to propose two somewhat novel combinations of a few well-established practices. Their novelty lies in that they strive to make gains made by all involved parties commensurable in the absolute sense. The first is cooperative pharmaceutical research, while the secondis concerned with establishment of pharmaceutical cooperatives to make, distribute and sell quality generic medicines and diagnostic material on a non-profit basis.

Research cooperatives may consist of hospitals, universities, medical research institutes, and any other accreditedbody appropriate for the purpose.  It is preferablethat they are publicly funded. Source of their fundingis immaterial as long as all partners of a cooperative are willing to have the same share of the patent, and accept that takeovers are forbidden.

Pharmaceutical cooperatives may be national or multi-national, and in my view, they would be most effective if they are designed to providemedicines and diagnostic material for which its region has the greatest need. It could pool regional technical expertise and financial resources.

My next suggestion is concerned with dealing with the fact that forsome time to come, pharmaceutical cooperatives with the help of cooperative research will not be able to provide some medicines and diagnostic materials at a low cost, and it might not be easy to find the financial resources needed to establish them.

I propose the establishment of a UN Medical Supplies Development and Procurement Agency (UNMSDPA). A transparently run technical body, its purpose is to assist cooperative research and pharmaceutical cooperatives financially up to a point,  and to negotiate the prices of most needed medicines and diagnostic material for purchase, buy them and distribute them at suitably subsidised prices.

I have not described UNMSDPA at length, but the rationale behind its establishment as well as that of research cooperatives and pharmaceutical cooperatives, is to show some regard for human rights in practise. For millions of sick who need medicine, it is already too late, but, there are millions more to whom we can show what regard for human rights may mean in real life.

Limitations and Obstacles

The followingis a non-exhaustive list of limitations the present proposal will have to surmount:

1.  Shortage of people with the requisite analytic and synthetic skills with respect to holistic, hence fully congruent policy formulation.

2.  Availability of persons skilled in implementing congruent policies.

3.  Institutional barriers in place to safeguard institutional autonomy may limit inter-institutional coordination in practice.

4.  Willingness among the relevant organisations to engage in cooperative research as described.

5.  Willingness of national/regional producers to engage in cooperative pharmaceutical production as described, and if they are, their access to required funds.

6.  Great diversity among multi-governmental and NGO’s concerned with health, whose fragmented effort leads to inefficient use of resources, and would limitthe resources available to the proposals made here.

As for the obstacles one needs to overcome, the following are among the most significant:

1.  Tendency to place undue confidence in the so-called evidence-based approach, which practically excludes new ways simply because there cannot be any evidence of their adequacy.

2.  Geometric proliferation of data that blinds the planners and decision-makers precisely in the same way as one does not see the forest for trees.

3.  Difficulty in inducing the decision-makers and planners to adopt a holistic approach to problem solving.

4.  The implicit motivator of modern economy, viz., the possibility of making profit ad libitum, which effectively excludes the human rights considerations from it.

5.  Lack of willingness among international trade and economic organisations to revise their rules in a manner that promotes a more equitable economics.

6.  Sequestration of an undue share of the world’s nett financial resources in comparatively few private hands.

7.  Tendency among those working in global health to use reductive solutions on their favourite fields.

Moving Forward

Eliciting the global political willingness to undertake a collective humanitarian action to meet an obviously urgent need seems to be the only way of countering the limitations and obstacles this proposal would meet. A meeting of political leaders on the issue may be of some use here.

Extensive dissemination of plain information on the extent of actual suffering of millions owing to lack of medicines and diagnostic material may induce the public to demand helpful changes in governmental perception.

In conclusion, vaccination has been excluded because of the existing successful endeavours to promote it. However, some vaccine production may be incorporated into the proposed scheme. I think it is time to admit to ourselves, we fail not for the lack of resources, but for our unwillingness to use them as we ought.

Bibliography and References

On linkages among health, nutrition and environment, please see:

http://www.fao.org/fsnforum/cfs-hlpe/node/992

http://www.fao.org/fsnforum/cfs-hlpe/node/1043

Butoyi Florence, Women's Hope Association

Name of Lead Author: Butoyi Florence
Organization: Women's Hope Association
Country: Burundi

Abstract

My contribution is concerned generally to Burundian women who are contaminated by the viral hepatitis.Those women needs help for the vaccination.they are not able afford medicines of that diseases because of the poverty.Medicines are rarely found and many people died luck of the vaccination and also because they are poorest women for accessing to health care.consequences of that, is that orphans are so many, because their parents have been died.

Submission

For access to medicine, in our country, access to medicine is not fair, more than 80 percent of Burundi's population life in the countryside where there are health centers Scattered where staff is not well trained. Because these health centers are built over a long distance, some resort to traditional medicine. Large hospitals, they are not concentrated in large cities than in cities of provincial capitals but in very small quantities in these hospitals, the services offered are very expensive when compared with the purchasing power of the population that making it a major part of the population access unavailable to seek treatment- As for vaccination, lasts only our country made a lot of effort to fight against diseases but problems abound as no vaccine for viral hepatitis.
- As for diagnosis, our country still lacks laboratory (molecular biology), medical imaging, and so forth to diagnose certain diseases. Patients are transferred abroad or medicine is very advanced.
- As for technology, our country suffers greatly from a lack of modern equipment necessary to satisfy the needs of patients.
Even the staff is not enough, patients are still dissatisfied several diseases are diagnosed.
In general, the field of medicine remains at a very low level if one tries to make an analysis.

My name is Florence , I am Burundian in the Bujumbura province exactly at CARAMA Commune.i have born in Burundi in 1983. I had finished my secondary school in 2010. From 2011 until now, I study at Hope Africa University in Burundi Bujumbura.I am the Women's Hope Association representative from 2011 until now.

N. Hassoun, Binghamton University

Name of Lead Author: N. Hassoun
Organization: Binghamton University
Country: United States

Abstract

Understanding key technologies’ impact on the global burden of disease is essential for policy makers to extend access on important medicines to achieve Sustainable Development Goal 3 and fulfill everyone’s human right to health. This proposal aims to address the misalignment between the rights of inventors, trade rules, international human rights law, and public health in promoting access to important health technologies. It does so by providing a new dynamic model measuring key HIV/AIDS, malaria, and tuberculosis (TB) medicines’ effect on morbidity and mortality.

A comprehensive and accurate model of medicines’ global health impact is important for evaluating performance, setting targets, guiding the distribution of scarce health resources, and advancing access to affordable medicines. The Global Health Impact (GHI) model currently evaluates the global impact of medicines for HIV/AIDS, malaria, and TB and aggregates this information by company, drug, and disease as well as country. It estimates disease impact in the absence of treatment using data on drug effectiveness (or, barring that, efficacy), disease incidence, patient treatment coverage, and the global burden of disease that remains after treatment. We propose to expand this highly accurate, and innovative, metric to advance the measurement and understanding of pharmaceuticals impact in promoting global health. The preliminary version of the GHI model was recently published in PLoS One. The proposed methodology underlying the new version of the model is described in the section on implementation, evidence, and innovation below.

Making the new model and data on medicines’ global health impact available to researchers, policy-makers, consumers, companies, and other key stake-holders will increase their abilities to promote global health. This will provide states, non-governmental organizations, and companies with the means to promote new market strategies as well as innovative health policies that aim to provide worldwide equal access to medicine. 

Submission

Advancing the Sustainable Development Goals and Human Rights to Health:
Evaluating Global Health Impact and Increasing Access to Essential Medicines 

1.      Overview

Understanding key technologies’ impact on the global burden of disease is essential for policy makers to extend access on important medicines to achieve Sustainable Development Goal 3 and fulfill everyone’s human right to health. This proposal aims to address the misalignment between the rights of inventors, trade rules, international human rights law, and public health in promoting access to important health technologies. It does so by providing a new dynamic model measuring key HIV/AIDS, malaria, and tuberculosis (TB) medicines’ effect on morbidity and mortality.

A comprehensive and accurate model of medicines’ global health impact is important for evaluating performance, setting targets, guiding the distribution of scarce health resources, and advancing access to affordable medicines. The Global Health Impact (GHI) model currently evaluates the global impact of medicines for HIV/AIDS, malaria, and TB and aggregates this information by company, drug, and disease as well as country [1-6]. It estimates disease impact in the absence of treatment using data on drug effectiveness (or, barring that, efficacy), disease incidence, patient treatment coverage, and the global burden of disease that remains after treatment [7-97]. We propose to expand this highly accurate, and innovative, metric to advance the understanding of pharmaceuticals’ impact in promoting everyone’s human right to health [65-68]. The preliminary version of the GHI model was recently published in PLoS One [1]. The proposed methodology underlying the new version of the model is described in the section on implementation, evidence, and innovation below. Making the new model and data on medicines’ global health impact available to researchers, policy-makers, consumers, companies, and other key stake-holders will increase their abilities to fulfill individuals’ human rights to health.. The model will also provide states, non-governmental organizations, and companies with the means to promote new market strategies and innovative health policies to help achieve Sustainable Development Goal 3.

2.      Helping to Achieve Sustainable Development and Fulfill the Human Right to Health: Impact on Public Health and Policy Coherence

The GHI model can be used to help achieve Sustainable Development Goal 3 and fulfill individuals’ human rights to health [98-104]. It creates a common framework for judging health impact across a wide variety of interventions for multiple actors including private companies and international health organizations. It can thus help achieve universal access to quality essential health-care services as well as effective and affordable essential technologies. In particular, it can help address the epidemics of HIV/AIDS, malaria and TB. In doing so, it will also help reduce deaths of children under 5 years of age as malaria is a major contributor to these deaths. Moreover, the model can also be expanded to help address neglected tropical diseases as well as other communicable and non-communicable diseases.  

One way the model can be used to help address the epidemics of the diseases it evaluates is by highlighting the importance of paying attention not just to the burden of disease, but also its alleviation. Consider the need vs. impact graphs for HIV/AIDS from a preliminary version of the new model for 2010 (the methodology for the new model is described briefly in the appendix). The “Need” and “Impact” graphs below use Disability Adjusted Life Years (DALYs) as the basis for measuring need and impact. Globally, the data shows that there is a great amount of unmet need in the HIV/AIDS epidemic. Identifying current shortcomings is one step in identifying what can be done differently in order to address such shortcomings.

Need for and Impact of HIV/AIDS Medicines Around the World 

Fig 2. Estimated Global Burden of Disease in the Absence of Treatment (in DALYs) for HIV/AIDS and Estimated Impact (in DALYS) for HIV/AIDS

While inadequate access to medicines for diseases such as HIV/AIDS receives significant media attention, understanding of the access to medicines issue is hampered because there is currently no systematic way to quantify efforts to address this problem. Without the ability to objectively, and accurately, measure and understand access inequality and efforts to improve it, this issue is difficult to prioritize from both the policy and innovation perspective. The proposed work to expand and utilize this model to evaluate the impact of various policies for promoting access to essential medicines will generate both data and a methodology for rating efforts to extend access on essential medicines that quantifies the effectiveness and impact of investments. It will do so using an analytical framework that can be applied to a broad array of other contexts where there are significant positive externalities of industry innovation and a “public goods” component to discovery. This framework can stimulate the access movement in three critical arenas: the market (allowing consumers to easily identify those companies whose products are having a large global health impact), policy creation (providing policy-makers the evidence-base needed to measure, understand, and respond to this issue), and industry (this metric will recognize and encourage investments that address this problem).

Our new model can help illustrate the impact of attempts to fulfill the human right to health and advance the Sustainable Development Goals. This data will provide some transparency into efforts to extend access to essential medicines, allowing policy makers to better target resources [6]. It will also provide useful information for customers (caregivers and patients), investors, pharmaceutical companies, and researchers interested in pharmaceutical research and development (R&D) and promoting global health. The new model can, for instance, help researchers to identify conditions that potentially influence drug impact so as to promote scientific progress through a new monitoring tool. Using the data we provide, researchers might evaluate the value of different investments or policy instruments’ effectiveness in terms of global health impact. They might consider the impact of medicines’ patent status (on or off-patent) on global health. Alternately, they can consider whether open access licensing was used, etc. They can also study the processes and structures that generate innovation and, so, good health outcomes.

Consider how the model can help set targets and monitor countries’ performance in utilizing the flexibilities to protect public health, and provide access to medicines for all, in the Doha Declaration on the World Trade Organization’s Agreement on Trade Related Aspects of Intellectual Property Rights’ (TRIPS’). Researchers can evaluate the impact of countries’ efforts to take advantage of these flexibilities and expand access to important health technologies for these diseases. Insofar as they are successful, these technologies’ impacts should increase in the model helping achieve universal access to quality essential health-care services and access to safe, effective, quality and affordable essential technologies for these diseases. So the model can help set targets and measure performance in fulfilling the human right to health and advancing the Sustainable Development Goals.

In summary, this ground-breaking research will show that it is possible to collect and analyze new and important data on access to essential medicines. It will spur knowledge generation by evaluating the health returns on investments in pharmaceutical research and development. The resulting rating system will provide useful information for evaluating the structures and processes that help create new knowledge and innovation. It will also show how such structures impact an important social outcome – in particular, global health. Although data alone will not solve any of the health problems people face, it can be used to help many people secure essential medicines that save millions of lives every year.

3.      Implementation, Evidence, and Innovation

We have built a team of experts in health outcomes research, econometrics, biostatistics, and computer science and have an advisory board of representatives from academia and civil society from around the world to implement this project (global-health-impact.org). We are also working on outreach and soliciting feedback on the project from a variety of stakeholders. Once the scientific basis is well established, we will work on expanding our network to ensure that the model is used to evaluate policies and create incentives for a variety of agents to have a greater global health impact. Below is some information about our specific aims for developing the scientific basis for the model over the next few years.

The GHI model is currently the “gold standard” for evaluating the impact of key medicines for HIV/AIDS, malaria, and tuberculosis (TB) on disease burden in poor countries around the world [1-6]. Its methodology is significantly different than that embodied in other models as it estimates in a simple, transparent, and consistent way the health consequences of drugs for several leading diseases in global poverty areas [7-11]. Gathering data by company, drug, disease, and country into a single index, the original GHI model is able to estimate disease burden for any one or all conditions. 

While the original GHI model is an excellent first step to understanding the impact of major pharmaceuticals on these diseases, it fails to estimate the burden of disease that occurs in the absence of treatment, the impact of drugs on this burden over time, or consider the contribution of generic firms to alleviating the burden. Here is a diagram illustrating the conceptual basis for the new proposed GHI model:

Fig 1. The New Conceptual Model

We assume that the global burden of disease that remains after treatment (in DALYs lost) is the average impact of an untreated or ineffectively treated case times the number of such cases. We also assume that treatment impact (DALYs saved) equals the number who are effectively treated times the average impact of an untreated or ineffectively treated case. We will use this fact and an estimate we derive of the number untreated or ineffectively treated (from data on treatment percentage and efficacy) to back out an estimate of the average impact of an untreated or ineffectively treated case. The average impact of an untreated or ineffectively treated case = Global Burden of Disease / (number untreated + the number ineffectively treated). Then using our estimate of the number who are effectively treated, we can calculate the impact of treatment. This is the average impact of an untreated or ineffectively treated case * the number of people who need a drug who are treated effectively [see appendix for further information on the model].

We will draw on the expertise of health outcomes researchers, pharmacologists, biostatisticians, and econometricians to construct, analyze, and validate this more sophisticated index that will measure health in the presence and absence of treatment for over time [105-126]. This new index will produce data on worldwide access to essential medicines that can be used to generate strategies for providing more equal access to these medicines and scientific innovation to address important global health problems. More generally, this information can help fulfill individuals’ human rights to health and achieve Sustainable Development Goal 3.

For further information about the preliminary models and the principles on which the contribution is based, see: [1-6, 127]. These contributions also detail important limitations of the models. Our analysis will not, for instance, perfectly capture the volume of each product used in each country. Where data is lacking, an estimate is provided based on the extent to which products are listed as first-line drugs for treating a disease. If 100 patients are treated in a country, and there are two first-line drugs, each drug is given credit for its potential impact on 50 patients. Our approach has the merit of allocating credit for being recognized as a first-line therapy for a given disease. Similarly, we will not attempt to determine what the incremental benefit of a drug is, relative to the next best therapy. Our analysis, in effect, indicates the impact of treatment including drugs in place of no treatment. Even with the inaccuracies that inevitably arise in this exercise, we believe that it is important to understand and illustrate what impact pharmaceuticals are having on global health and that this project can create incentives for promoting sustainable development and the human right to health [128]. Sensitivity analysis of the preliminary version suggest that many of the assumptions have little impact on the model [1].

The GHI model’s methodology is significantly different than that embodied in other models of disease burdens [7-11, 74-75]. The Futures Institute produces several dynamic models focused primarily on HIV/AIDS. Their AIDS Impact Model (AIM), for instance, looks at “the consequences of the HIV epidemic, including the number of people living with HIV, new infections, and AIDS deaths by age and sex; as well as the new cases of tuberculosis and AIDS orphans” [74]. Their Prevention of Mother-to-Child Transmission (PMTCT) model “evaluates the costs and benefits of intervention programs to reduce transmission of HIV from mother to child” including information on seven possible treatment regimens as well as other interventions [74]. Their Lives Saved Tool (LIST) considers the impact of different child health interventions on child mortality. Most models do not use DALYs, but focus on mortality rates, and so leave out a large component of interventions’ impacts.

The Futures Institute’s models rely on different kinds of information and make different assumptions than the new GHI model will employ. AIM assumes information “about the past and future course of adult HIV incidence and treatment coverage” as well as “the survival period from HIV infection to AIDS death, the age and sex distribution of new infections, and the perinatal transmission rate” [74]. Moreover, there are many additional assumptions in the demographic model upon which AIM draws that differ from the assumptions implicit in the new GHI model [74].

The GHI model has several advantages over alternative models. None of the other models combine – in a simple, transparent, consistent way – estimates of the death and disability saved by medicines for HIV/AIDS, malaria, and TB [7-11,74,75]. Because it uses the IHME’s DALY information, the new GHI model includes comparable estimates of the interventions’ impacts on disability as well as death across several diseases. The new model also includes many more interventions than most models and aggregates this information by company, drug, and disease as well as country.

High quality data on health impact will improve global governance for health, making it more transparent and accountable. The AIDS crisis revealed problems with global health structures that posed barriers to reducing infections. To address these problems, recent conceptions of development expressed, for instance, in the Paris Principles have emphasized the importance of achieving “measurable health improvements.” This aim is embodied in relatively recent global public/private partnerships advancing the global health agenda by employing performance-based mechanisms for allocating assistance. The Global Fund reports that it has helped save 17 million lives and the GAVI Alliance reports that it helped save 5.5 million. Comparative evaluation facilitates learning across programs and countries, and induces change: governments are much more likely to improve programs when the shortfalls are known and there are demonstrably better approaches. Other organizations can also use this data to expand access to essential medicines around the world.

Several things are necessary to ensure that the project promotes sustainable health outcomes. A sustainable funding stream would allow us to scale up the model even further and improve the scientific analysis behind the project. Expanding our network to partner with international institutions and governmental and non-governmental agencies working on promoting access to essential medicines would ensure that the data is presented in a way that is most useful for efforts to expand access.

4.Conclusion

The Sustainable Development Goals, in setting the post-2015 development agenda, are refocusing efforts on universal health coverage and access to essential medicines. As in other areas, information is the key to success in improving health outcomes and fulfilling individuals’ rights to health. A broad, accurate picture of what we have achieved in extending access on essential medicines is necessary to guide national and international organizations. The Global Burden of Disease project has, over the past 20 years, been immensely valuable in illuminating areas of need and it has had an undeniable influence on health spending. There is no similarly comprehensive effort to evaluate the impact of funding and interventions to improve global health. According to the WHO-WB framework for measuring UHC “the post-2015 agenda should address the unfinished agenda of the health-related MDGs as well as the emerging burden of chronic conditions and injuries (CCIs)” and this evaluation should eventually be extended to address the global priorities embodied in the Sustainable Development Goals. Ideally the evaluation would include preventative and diagnostic technologies as well as treatments for SDG priority health conditions [129-130].

There would moreover be multiple, important uses for such data among numerous stakeholders—ranging from international institutions like the World Health Organization to bilateral or multilateral health assistance organizations like The President’s Emergency Program on AIDS Relief and philanthropies like the Gates Foundation to national governments. Good data about effectiveness can help international and multilateral institutions (and other stakeholders) prioritize funding across countries, diseases and interventions. Country-level health systems similarly aim to allocate their resources, and secure new resources, to have a greater impact. Comprehensive data is important for evaluating performance, setting targets, and guiding the distribution of resources. Expanded models might complement existing work by global development agencies using tools like LiST to assess the impact of important health interventions [131]. If, for instance, countries can see how drugs impacts would change as they are made more accessible, that would help them decide whether to invest in efforts to lower prices or extend access more broadly in other ways. Moreover, impact assessments may help shape policies linked to broader macroeconomic and trade liberalization aspects of globalization and improve global health governance [132].

The High-Level Panel on the Post-2015 Development Agenda called for “a data revolution” to “help guide decision making, update priorities and ensure accountability” [133]. Good information systems are just as important to fulfilling individuals’ human rights to health as diagnostic tests are for identifying and treating disease. As the world sets its sights on achieving sustainable development with the Sustainable Development Goals, it is important to collect new data that can guide these efforts. Millions of lives hang in the balance.

Appendix, References and Bibliography
 

Appendix

More formally, consider a patient group identified by the IHME’s GBD data [63,77-78], for example, patients affected by a given disease indexed by j in a given country indexed by k. For this group, define  as the average impact per untreated patient of the disease in terms of DALYs lost. Similarly, define the treated impact as

where

In effect, 

is the effectiveness of the treatment, relative to the baseline of no treatment. For example, a drug that reduces DALYs lost by 95% would have

The DALYs observed within the patient group by the IHME’s GBD study are given by (1)

where  

represents the proportion of infected persons who received treatment and n represents number of infected persons (i.e. the prevalence of disease times the population). (We have suppressed subscripts.) Assuming that treated and untreated individuals are similar, except for treatment, the DALYs that would occur in the absence of treatment is simply

(2)

Therefore the impact of treatment is given by

(3)

where this negative number represents a reduction in DALYs. Rearranging (1) we obtain

(1*)

Substituting (1’) into (3), we can write the impact of treatment as

(4)

The contribution of drug m to treatment regimen i with  drugs is assumed to be an equal share of the regimen, and the impact of the drug is therefore simply given by 

(5)

In effect, using this approach, we can identify the impact of treatment with a given regimen using (a) data from the IHME’s GBD study, (b) information on coverage of the patient population with a given regimen and (c) the effectiveness of the regimen compared to no treatment. Current treatments for HIV/AIDS, TB, and malaria are quite effective, and e may therefore typically be expected to be in the range [0.8, 1]. 

Coverage 

is written as a stock, but in many cases treatment takes time, and so coverage should reflect the proportion of the patient population that is completing treatment. We will therefore adjust coverage by dividing it by the average duration of treatment if this number exceeds one year. Further details of the methodology specific to each disease and data sources are below.

Let’s use an example to illustrate how the impact score of a drug for one country can be calculated. Consider Artemether Lumefantrine (AL) in Bangladesh. For Bangladesh, 191,646 DALYs were lost due to malaria in 2010 [78]. About 92% of malaria in Bangladesh is Plasmodium falciparum malaria [79]. So the DALYs lost to Plasmodium falciparum malaria was 92% of 191,646, or 176,314. AL is used as the first-line drug for Plasmodium falciparum malaria in Bangladesh [79]. The treatment coverage for AL is 0.3% [80] and AL is efficacious in about 91.70% of cases [81]. The impact score of AL is calculated using the simplified formula

For Bangladesh, the DALYs saved by AL as a first-line drug is 176,314*0.3%*91.7%/(1-0.3%*91.7%)=515.10. 

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Xavier Prats Monné, European Commission

Name of Lead Author: Xavier Prats Monné
Organization: European Commission
Country: Belgium

Submission

The European Commission welcomes the opportunity to address comments to the High Level Panel on Access to Medicines. Access to medicines is a complex issue with a multitude of factors affecting the accessibility, availability and affordability of safe quality medicines to patients around the worldš The European Commission addresses the access to medicines agenda with a health-in-all-policies approach and through various initiatives, programmes, and policy and financial support.

Currently, European Commission engagement and support for access to medicines addresses a wide range of issues including basic and applied research for neglected and orphan diseases, regulatory capacity building, health systems strengthening, transparent public procurement systems, increased capacities for local production and for detectionof falsified medicines, support for measures to root out corruption and to improving supply and distribution chains for pharmaceuticals. The Commission also supports the work of the WHO, including its normative work, on its lists of Essential Medicines and its guidance on rational use. This includes the implementation of the Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property (GSPOA) adopted by the World Health Assembly in 2008.

Other initiatives put in place in relation to affordability include the elimination of import tariffs for medicines and the encouragement of actions that provide economies of scale such as joint procurement actions for medicines and vaccines both directly at EU Member States level and indirectly though the significant contributions it makes to the Global Fund to Fight AIDS, Tuberculosis and Malaria and to GAVI, The Vaccine Alliance. The EU is a major contributor to health-related aid.

Against this background the Commission wishes to point out the importance of EU support to such projects and initiatives. The EU has also initiated the European and Developing Countries Clinical Trials Partnership to accelerate the development of new or improved drugs, vaccines, microbicides and diagnostics against HIV/AIDS, tuberculosis and malaria as well as other poverty-related and neglected infectious diseases in sub-Saharan Africa.

Within this broad picture, the Commission encourages the Panel to adopt a holistic approach to the problem so that it can make a valuable contribution to the wider debate on access to medicines. In this context, the European Commission does not share the starting assumption of the call for contributions - presented as a definitive conclusion - that there is a "misalignment between the rights of inventors, international human rights law, trade rules and public health where it impedes the innovation of and access to health technologies". Indeed, this assumption that the rights of inventors are the single or even the main impediment to innovation and access to health overlooks a key finding of the 2012 joint WHO-WTO-WIPO study on "Promoting Access to Medical Technologies and Innovation" that the "lack of access to medical technologies is rarely due entirely to a single determinant." As also reflected in the WHO access framework for essential medicines, there are many factors affecting access which are not related to intellectual property, such as lack of access to quality health care, poor infrastructure, lack of distribution and supply systems, and lack of quality control. Such a narrow starting point also ignores all the efforts and verifiable progress that have been made on the link between patents and access to medicines in the last 15 years.

 Intellectual property is a driver of innovation for new medicines and new uses for medicines. The question the Panel will face is how to balance the need for incentives for innovation with ensuring equitable access for patients. There is a significant amount of work going on globally in this area and the Commission urges the Panel to build on the work conducted by international organisations such as the WHO, the WTO, and WIPO on this issue. The Commission also draws the Panel's attention to the ongoing comprehensive evaluation and review of the above-mentioned GSPOA that will take into account relevance, effectiveness, efficiency and sustainability.

The Commission also wishes to recall that the international IP regime foresees a number of exceptions and options that can be used to improve access to medicines, as clarified notably in the 2001 Doha Declaration on TRIPS and public health. Key options include transition periods for least developed countries (LDCs) and a recent example of putting this into practice was the 6 November 2015 decision of the WTO's Council for Trade-Related Aspects of Intellectual Property Rights (TRIPS) that LDCs will be exempt from WTO obligations to provide patent protection for pharmaceutical products to support access to medicines until at least 2033, which was fully supported by the European Union.

Another important step was the decision by WTO members in 2003 to propose amending the TRIPS Agreement to make it easier for countries to import medicines produced under compulsory licensing if they are unable to manufacture the medicines themselves ("Paragraph 6 System"). The Commission would suggest the potential contribution of these measures is taken into account.2

 The Commission would encourage the Panel to assess the increased use of voluntary license agreements (e.g. through the Medicines Patent Pool) as a tool to increase the affordability of medicines, as well as to consider recent initiatives such as the WIPO initiative "Re:Search" - a consortium through which public and private sector organizations share valuable intellectual property and expertise with the global health research community to promote development of new drugs, vaccines, and diagnostics in the fight against neglected tropical diseases, malaria, and tuberculosis.

Finally, the European Commission would like to express its availability to work constructively with the Panel in the coming months as part of the broader debate on access to medicines but would insist that this, like all the work of the Panel, should be done in a transparent manner.