Agnès Binagwaho, Richard Freeman, Kirstin Scott, Anne Badrichani, Sardis Harward, Monique Mulindahabi, Corine Karema

Published April 14, 2015

The procurement of high-quality medicines to combat major causes of avoidable suffering in sub-Saharan Africa—such as HIV/AIDS, malaria, and tuberculosis—is instrumental to a nation’s health system.  Such products are indispensable for national systems to provide the highest attainable standard of health, a fundamental human right. The growth of international aid over the past decade to assist low-income countries in obtaining these life-saving medicines has been critical to such efforts. With this influx of billions of dollars in aid, however, it has been necessary to develop regulatory processes to ensure the safety and effectiveness of the purchased medicines. This is especially pertinent for countries with weak regulatory systems, which are unsurprising targets for the unfortunate market of counterfeit medications. Annual global earnings from the sales of counterfeit and substandard medicines are estimated to exceed US $30 billion.[1]

The United Nations’ (UN) Prequalification of Medicines Program (PQP), which is managed by the World Health Organization (WHO), is making a noteworthy effort to help fill this regulatory gap in low-income settings and ensure effective, safe medications and products for widespread conditions that affect too many lives. Countries that rely on international aid, such as that administered through the Global Fund to Fight AIDS, Tuberculosis and Malaria, are generally required to purchase only those products that have the WHO PQP stamp of approval. These measures are intended to help ensure that the limited aid dollars for diseases such as malaria are not wasted on substandard medications or products.  They are also designed to mitigate harm to vulnerable patients.

Accordingly, the PQP program is well-aligned with the UN’s “Protect, Respect and Remedy” Framework for Business and Human Rights, which aims to ensure respect for human rights in commercial transactions, including those made by public health sectors.[2] Ensuring respect for the Guiding Principles and the integrity of the accompanying regulatory system is therefore of paramount importance to a health system’s goals to fulfill health as a human right.[3] As WHO Director General Margaret Chan has said, “The world needs a global health guardian, a custodian of values, a protector and defender of health, including the right to health.”[4] The PQP program is intended to be, and is marketed as, one such guardian.

But what happens when such regulatory systems do not address all quality issues?  The consequences are likely harshest for the end users of substandard, or worse, unsafe products that have the appropriate approvals but are not efficacious.  Those consequences are not limited to health effects alone; patients may lose trust in a health system that delivers ineffective treatments and services. Furthermore, one should not overlook the time, money, opportunity costs, and investment required of an already resource-limited health system to purchase replacement products, remove the ineffective ones from the market, and then redistribute materials to the population. These all have consequences for the realization of the human right to health. But who is responsible for these costs and health consequences? Is it the manufacturer? The regulatory entities?  The State’s health system that distributed the approved product?  Is it the international donor who requires recipient countries to purchase only those medications and consumables that fall on a particular list of pre-qualified products?

A case study from Rwanda demonstrates that these questions are both highly important and non-hypothetical. In 2012, this low-income country of 12 million people in East Africa witnessed a significant rise in confirmed malaria cases. As it has done effectively in the past, it followed the steps outlined in its national strategic plan for malaria control to combat this disease, including a massive campaign to distribute malaria bed nets to those most vulnerable.[5] When cases did not subside, as they had historically done in response to these efforts, the Ministry of Health (MOH) investigated the issue further with a series of epidemiological studies.

One of the incriminating factors emerging from this investigation was the unfortunate finding that a type of bed net that had been widely distributed across the country, and had the appropriate WHO pre-qualification approvals before shipment, did not meet these standards and thus had low bioefficacy.[6] Rwanda, and every other country relying on this type of pre-qualified bed net, eventually learned from the WHO Pesticide Evaluation Scheme working group that this particular bed net was of substandard quality and should be removed from the prequalified list.[7] There was a concerning 4-month delay between the scientific experts’ recommendation (from which countries like Rwanda are required to select their antimalarial products) and release of the published, publicly available report.[8] Though Rwanda had already started to remove the bed net from circulation prior to the release of the report, remedial action could have been taken much sooner to ensure the bed net was no longer being purchased or distributed in countries with high malaria disease burdens and limited financial resources with which to combat them.[9]

This incident was not unique. It is reminiscent of another case related to malaria diagnostic tests. In October 2010, inspection of a manufacturing facility producing HIV tests and Paracheck, one of the most commonly used malaria rapid tests, was carried out by the WHO Prequalification of In Vitro Diagnostics Programme, which uncovered “critical non-conformities.”[10] WHO made a second inspection a year later and found even more severe violations of quality standards. However, another eight months passed before WHO finally disclosed the information to Member States in July 2012, almost two years after first learning of the problem.[11]

Such delays in notification and alerts simply cannot be ignored. Both instances resulted in real health consequences. They also had real economic costs to Rwanda (and potentially to other countries) as the country had invested its limited financial resources in purchasing these products, only to have to remove them and bear the unnecessary health and related consequences. Moreover, such delayed reactions to the misconduct of manufacturers and failure to disclose this information to Member States in a timely manner erode trust in the regulatory process and compromise States’ ability to protect health as a human right. Knowing that countries and international organizations such as the Global Fund rely upon the prequalified list of drugs and consumables to purchase life-saving products, it is critical that the world better understands the scope of these delays, the reasons behind them, and how they can be remedied in a meaningful way.

The right to health should manifest in the day-to-day work of the WHO, including the business transactions it makes with vendors who develop products used to address major global health priorities. The UN’s Guiding Principles on Business and Human Rights assign States’ an affirmative duty to “protect” human rights, and they assign businesses a duty to “respect” those rights by avoiding harmful conduct.  The Guiding Principles clearly state: “…States should exercise adequate oversight, in order to promote human rights in the business sector and meet their international human rights obligations when they do commercial transactions with, or legislate for, business enterprises to provide services that may impact upon the enjoyment of human rights…”[12]  Given the examples above, however, one must ask how States can fulfill their duty when international normative agencies fail to release timely, actionable, and scientifically based information.

States are not directly responsible for human rights abuses by the private sector, but do breach their international human rights obligations if “they fail to take appropriate steps to prevent, investigate, punish and redress private actors’ abuse…”[13] States also have the obligation to “…facilitate public awareness and understanding.”[14] These statements should also apply to global health organizations because 1) the “duty to protect” is not just a contractual provision, but an ethical norm, and 2) the Guiding Principles make it clear that States do not lose their responsibility to protect human rights when they enter a multilateral institution, and represents a grouping of such States.[15] When the organization fails in its mission and obligations to take timely, appropriate steps that can help States to prevent, investigate, and redress private actors’ negligence or misconduct, however, such activities cannot be ignored or excused as an unfortunate but acceptable byproduct of bureaucracy.

At a minimum, when an international regulatory agency plays a role in the manufacturing process and the supply chain side of vital commodities, it should accept the minimal responsibility of businesses: the “corporate responsibility to respect” human rights.[16] Specifically, UN agencies should not withhold information when such a reporting delay would undermine Member States’ effort to implement programs that protect human rights.

WHO should expedite efforts to facilitate Member States’ awareness and understanding when a human right to health is threatened through materials found to be substandard yet previously approved by its regulatory entities, as occurred in the two aforementioned cases. A first step may involve assessing the scope of notification delays. Greater understanding of the scope and sources of such delays may inform new processes could be put in place to improve communication channels between WHO and Member Countries when scientific working groups come together to assess the effectiveness of life-saving treatments or tools. Second, WHO could implement a policy requiring the Secretariat’s agencies to rapidly disclose to Member States the opening of a product investigation. Such a rapid disclosure would not necessarily reveal all details of the post-market surveillance. It would simply provide transparency, give Member States more reasonable notice, and trust that rational Members will exercise appropriate restraint before a final report is completed. Disclosing an investigation would have the additional benefit of increasing vigilance among Member States (e.g., informing existing or developing pharmacovigilance programs), and could result in the contribution of additional data that would benefit all.[17] Lastly, the Secretariat’s agencies could incorporate criteria for timely reporting requirements into the protocols for agency audits and staff performance reviews. Agencies and individuals should be held accountable by WHO’s internal mechanisms when their work fails to uphold the organization’s mission.

Greater international accountability is needed among all actors—from international organizations to private-sector manufacturers to recipient countries—to ensure that the global health community can fulfill the goal of promoting the highest attainable standard of health as a human right. This goal cannot only represent a verbal commitment, but must also translate into action.


Agnès Binagwaho, MD, M(Ped), PhD, is Minister of Health of the Republic of Rwanda, Kigali, Rwanda, Senior Lecturer at Harvard Medical School, Boston, MA, USA, and Clinical Professor of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.

Richard Freeman is Researcher at Stanford Law School Rule of Law Program, CA, USA.

Kirstin Scott, MPhil, is a PhD Candidate in Harvard’s Health Policy Program, Boston, MA, USA.

Anne Badrichani, PhD, is an independent consultant, USA.

Sardis Harward, MPH, is a Research Fellow with the Dartmouth Center for Health Care Delivery Science, Hanover, NH, USA.

Monique Mulindahabi, MD, MSc FELTP, is member of Malaria and Other Parasitic Diseases Division-Rwanda Biomedical Center, Ministry of Health, Rwanda.

Corine Karema, MD, MSc, is Director of Malaria and Other Parasitic Diseases Division- Rwanda Biomedical Center, Ministry of Health, Rwanda.


References

[1] World Health Organization, Substandard and counterfeit medicines (2003). Available at http://www.who.int/mediacentre/factsheets/2003/fs275/en/.

[2] United Nations, Protect, Respect and Remedy Framework and Guiding Principles. Available at http://business-humanrights.org/en/un-secretary-generals-special-representative-on-business-human-rights/un-protect-respect-and-remedy-framework-and-guiding-principles.

[3] Ibid

[4] World Health Organization, The right to health. Available at http://www.who.int/mediacentre/factsheets/fs323/en/.

[5] C. Karema, M.W. Aregawi, A. Rukundo, et al, “Trends in malaria cases, hospital admissions and deaths following scale-up of anti-malarial interventions, 2000–2010, Rwanda.” Malaria Journal 11/1(2012), p. e236.

[6] Ministry of Health, Rwanda. MOH Reports (2014). Available at http://moh.gov.rw/index.php?id=99.

[7] World Health Organization. Report of the Sixteenth WHOPES Working Group Meeting (July 2013). Available at http://apps.who.int/iris/bitstream/10665/90976/1/9789241506304_eng.pdf.

[8] A. Binagwaho and C. Karema, “A call for international accountability—preserving hope amid false protection.”Lancet Global Health 3/4 (2015), pp. e188–9.

[9] Ibid

[10] Ministry of Health, Rwanda. MOH Reports (2014).  Available at http://moh.gov.rw/index.php?id=99.

[11] World Health Organization. WHO Prequalification of Diagnostics – Notice of Concern – Tulip Group (2012). Available at http://www.who.int/diagnostics_laboratory/procurement/120720_noc_tulip_group.pdf?ua=1.

[12] United Nations (see note 2). p.8.

[13] Ibid., p.3.

[14] Ibid., p.28.

[15] Ibid., p.3.

[16] Ibid., p.13.

[17] World Health Organization. Pharmacovigilance. Available at http://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/.

 

Copyright: © 2015 Binagwaho, Freeman, Scott, Badrichani, Harward, Mulindahabi, Karema. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

 
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