Info Service on Health Issues (Oct14/03)
WHO’s antibiotic resistance draft action plan soft on critical issues
New Delhi, 16 October (K M Gopakumar) – A draft global action plan on antimicrobial resistance is soft on critical issues of innovation, access to new antimicrobial medicines, and regulation of promotion and marketing of such medicines.
Though there are some references in the draft prepared by the World Health Organization (WHO), the details do not affectively address these critical concerns. Crucial concerns especially of developing countries have not been explicitly addressed.
The 67th World Health Assembly (WHA) in May 2014 mandated the WHO Secretariat “to develop a draft global action plan to combat antimicrobial resistance, including antibiotic resistance, which addresses the need to ensure that all countries, especially low and middle income countries, have the capacity to combat antimicrobial resistance and which takes into account existing action plans and all available evidence and best practice as well as the recommendations of WHO’s Strategic Technical Advisory Group on antimicrobial resistance and the WHO policy package to combat antimicrobial resistance”.
The WHA resolution asks Member States (a) to commit to a comprehensive, financed national plan with accountability and civil society engagement; (b) to strengthen surveillance and laboratory capacity; (c) to ensure uninterrupted access to essential medicines of assured quality; (d) to regulate and promote rational use of medicines, including in animal husbandry, and ensure proper patient care; (e) to enhance infection prevention and control; (f) to foster innovation and research and development for new tools.
The resolution requested the WHO Director General “to apply a multisectoral approach to inform the drafting of the global action plan, by consulting Member States, other stakeholders including the international organizations such as Food and Agricultural Organization (FAO) and the World Organization for Animal Health (OIE)”. However, it cautioned the DG to take into account the need to manage potential conflicts of interest (For further details see: http://www.twn.my/title2/health.info/2014/hi140506.htm).
The Global Action Plan (GAP) is to be submitted to the 68th WHA through the 136th Session of the Executive Board meeting which will take place on 26 January to 3 February 2015 in Geneva.
The Secretariat is organizing an informal consultation of Member States on 16October for the further development of GAP. The informal consultation will be followed by the meeting of WHO’s Strategic Technical Advisory Group on Antimicrobial Resistance (STAG) on 17October.
The Secretariat is to take inputs from these two meetings before it firms up the draft for the consideration of the upcoming WHO Executive Board in January 2015.
The draft GAP contains six parts viz. preparation of the draft action plan, background, action plan goals, principles and strategic objectives, actions to achieve the strategic objectives and implementation, monitoring and evaluation.
The first part - preparation of the action plan - provides the process of the preparation of GAP. It lists the past consultations on anti-microbial resistance (AMR) where the Secretariat either organized or participated in order to obtain inputs. This includes the STAG meeting on 14-16 April 2014, regular consultation with FAO and OIE and web-based consultation in July and August. It also lists the two Member States-organized events: Ministerial Conference on Antibiotic Resistance (25-26 June in The Hague), and the Global Health Security Agenda Meeting that included AMR (20-21 August, Jakarta). It also lists the future consultation to be organized by various Member States. These include: meeting to address research gaps and needs to be hosted by Brazil (28-29 October 2014, Brasilia); Responsible Use of Antibiotics to be co-hosted by Brazil, France, Indonesia, Norway, Senegal, South Africa and Thailand (13-14 November 2014, Oslo); and a meeting to promote development of global surveillance capacity, systems and standards to be hosted by Sweden (2- 3 December 2014, Stockholm).
The second part provides the back ground of AMR and its implications for various sectors. This includes patients and families; health care workers; farmers, animal husbandry and the food industry; pharmaceutical sector and economic policy makers, development agencies, research funding organizations and other potential investors. It states that many required actions to address AMR depend on the political will to “adopt controversial policies, including controlling the use of antimicrobial drugs in human health and animal and food production”.
The third part sets out the goals of GAP. The overall goal is “for as long as possible, continuity of treatment and prevention of infectious diseases with effective and safe medicines that are of appropriate quality, used in a responsible way, and accessible to all who need them”.
It also proposes outcomes and impact to monitor the effectiveness of GAP. These are: A reduction in the prevalence of AMR, based on data collected through integrated AMR surveillance program and infectious disease control programs; a reduction in the mortality attributable to AMR; a reduction (to zero) in the number of serious infectious diseases that cannot be prevented or treated; a reduction in the prevalence of selected infectious diseases and in particular preventable infections; an increase in the number of organisms for which specific rapid diagnostic tests are available; the number of new medicines entering phase II clinical trials studies and for which mechanisms are in place to ensure preservation, and access in low- and middle- income countries; a reduction in global human consumption of antibiotics, recognizing the need for improved access in some settings, with specific reporting of the use of critical classes of antibiotics and other antimicrobial medicines; a reduction in the consumption of antibiotics used in food production, progressive reduction (to zero) in the use of medical and veterinary antimicrobial applications other than human and animal health.
The fourth part provides the principles and strategic objectives of GAP. The six guiding principles are: whole –of society engagement; actions based on best available knowledge and evidence; prevention first; access not excess; sustainability and incremental targets for the implementation. This parts also lists the five strategic objectives. These are : improve awareness and understanding of AMR through effective communication, education and training; strengthen the knowledge and evidence base through research and surveillance; reduce the incidence of infection through hygiene and infection prevention measures; optimize the use of antimicrobial medicines in human and animal health; develop the business case for sustainable investment that takes account of the needs of all countries, as well as the need for investment in new medicines, diagnostic tools, vaccines and other interventions.
The fifth part on actions to achieve the strategic objectives provides the details of the required action. The actions are divided among Member States, the Secretariat, and international and national partners. The international and national partners include other intergovernmental organizations such as FAO, OIE, the World Bank etc and non-state actors such as civil society organizations (CSOs), non-governmental organizations (NGOs), and trade and industry bodies.
The draft GAP fails to provide bold solutions especially where the pharmaceutical transnational corporations (TNCs) and their home countries have vested interests.
Some of these areas are mentioned below.
Access and Affordability
One of the important concerns related to AMR is the access to antimicrobial medicines including antibiotics and diagnostics at affordable prices. Often, lack of affordability contributes to resistance because people often do not complete the full course of the treatment due to high prices of the medicines. Generally speaking, there are two concerns related to access viz. access to new antimicrobial medicines and diagnostics, and access to existing antimicrobial medicines that are highly priced.
New antimicrobial medicines and diagnostics often come into the market with patent protection. The patent holder abuses the patent monopoly and charges exorbitant prices and denies access to majority of people in developing countries. Further, patents also prevent market competition through the entry of generic competition.
Gilead Sciences charging an exorbitant price for its new medicine for the treatment of Hepatitis C drug Sofosbuvir. It charges USD 84,000 for a 12-week treatment.Recently Gilead issued a Voluntary Licence to nearly seven Indian manufactures to produce and market the medicine in 92 selected countries excluding 51 middle income countries having about 50 million people infected with Hepatitis C. (According to the WHO itself, 75% of the world’s poorest people live in middle income countries.)
Part three on action plan goals mention access. It states that the monitoring of the effectiveness of the action plan would depend on, among other things, the number of new medicines entering phase II clinical studies, and for mechanisms to be in place to ensure preservation, and access in low and middle income countries as well as the increase in number of diagnostic tests and its use in low and middle income countries. Further, it talks about a reduction in the human consumption of antibiotics while recognizing the need for improved access in some settings. However the draft GAP does not elaborate on “some settings”.
[It is worth noting that WHO is shifting away from the traditional UN classification of developing and least developed countries to low and middle income countries, see WHA 67.25.]
Even though it mentions access in low and middle income countries, it does not explain the mechanism to ensure access to new antimicrobial medicines and diagnostics in developing countries. The most important tool to address the challenge of patent monopoly is the use of TRIPS flexibilities, which includes compulsory license and government use orders. The WHO Member States have adopted the Global Strategy and Plan of Action on Public Health Innovation and Intellectual Property at the 2008 WHA, which provides a mandate to the Secretariat to enhance the capability of member states to use the TRIPS Flexibilities as well as to promote technology transfer. The draft GAP is conspicuously silent on the use of TRIPS flexibilities.
The draft GAP introduces the concept of “access not excess” as a guiding principle. It further explains this guiding principle. It states: “the overall goal is to preserve the ability to treat serious infections. Actions to address AMR need to take into account the need to maintain equitable access to and appropriate use of existing and new antimicrobial medicines”. However, the document does not explain the ways and means to achieve equitable access. The important policy measures which can ensure equitable access is the availability of antimicrobial medicines and diagnostics at affordable price include local production capabilities of antimicrobial medicines and diagnostics, technology transfer and public procurement. The draft GAP is silent on all these three policy measures.
Part five of the draft which mentions concrete actions to achieve strategic objectives do not provide any clear direction on the access question. The strategic objective 4 – optimize the use of antimicrobial medicines in human and animal health – mentions access under proposed actions by Member States and the Secretariat. Under proposed actions by Member States it is proposed that access to antimicrobials should be only through prescription. There are references to access in section 5.4.2 where the Secretariat “undertook the responsibility to develop technical guidelines and norms to support access to, and evidence-based selection and responsible use of, antimicrobial medicines, including follow up treatment”. However no concrete action has been proposed to address access to affordable antimicrobial medicines and diagnostics.
Further section 5.5.2 (new investment and business model) states that the Secretariat would consult with Member States and the pharmaceutical industry on innovative regulatory mechanism for new antimicrobial medicines to address the need for preservation and global access. Affordability and access to new antimicrobial medicines and diagnostics are mentioned in section 5.5 on new investment and business models.
However, the specific actions for the Member States, Secretariat and international and national partners mentioned in subsections 5.5.1, 5.5.2 and 5.5.3 are silent on both affordability and access except for a passing reference in action by Member States. This reads: “Piloting innovative ideas for financing such R&D and for the adoption of new market models to encourage investment and ensure access to new antimicrobial products”. This is without mentioning any concrete ideas like the delinking principle i.e. delinking the cost of R&D from the price of product through new R&D models, including open innovation.
Similarly, there is no reference to access and affordability in Part six, which deals with implementation, monitoring and evaluation, especially in the proposed actions by Member States. Annex 1 of the document that contains the potential measures of the action plan implementation is also silent on access to affordable antimicrobial medicines and diagnostics.
This silence in a way goes against the Member States’ direction to the Secretariat in the resolution WHA 67.25.
Research and Development
Another major area of strategic silence is the research and development (R&D) of new AMR medicines including antibiotics and diagnostics. The draft GAP correctly observes that when it states in Part two that “current low levels of investment in R&D on antibiotics could suggest that the traditional investment model is failing patients in this area”. It further states that new business models are needed to incentivize innovation and promote cooperation between policy makers, researchers and the pharmaceutical industry to ensure that new technologies are available globally to prevent, diagnose and treat resistant infections”.
Part three of the draft GAP on action plan goals identifies the increase in “the number of organisms for which specific rapid diagnostic tests are available including for use in low and middle income countries”. It also talks about the number of new medicines entering into phase II clinical studies. However, the strategic goals are silent on the new R&D models and innovative funding mechanisms.
The strategic Objective mentioned in subsection 5.5 focuses on the need to develop the business case for sustainable investment that take account of the need of all countries, as well as the need for investment in new medicines, diagnostic tools, vaccines and other interventions. It cites the concern of the WHO’s Consultative Expert Working Group (CEWG) Report on R&D financing and coordination on the underinvestment in antibiotic development: “… new market models are therefore needed which will result in renewed investment in R&D, while also ensuring that use of new products is governed by public health needs within the framework of stewardship programs to conserve the products effectiveness and that there is equitable and affordable global access to them”. It also mentions the need for new and affordable diagnostic tests and its availability and use in low and middle income countries.
However, the proposed actions by the Member States are silent on the new R&D models to achieve both objectives of innovation and access. The CEWG Report makes clear references to the principle of delinking the cost of R&D from the price of the product using new R&D models such as open innovation. Instead of that the draft GAP proposes “international collaboration, strengthening of existing and creating new public private partnership for R&D, piloting innovative ideas for financing such R&D and for the adoption of new market models to encourage investment and ensure access to new antimicrobial products”.
Similarly the section on actions by the Secretariat proposes that the Secretariat explore with Member States, intergovernmental organizations, industry associations and other stake holders, options for the establishment of a new partnerships to “establish open collaborative models of R&D in a manner that will both ensure access and also provide incentives for investment”. This proposal in the light of past experience is a non-starter because a number of the developed country Member States and pharmaceutical TNCs do not want to move away from patent oriented R&D models. Therefore the Secretariat’s proposed exploration plan is unlikely to materialize. Instead the Secretariat should have offered its technical assistance to Member States to use new R&D models based on the delinkage principle.
It is also noteworthy that even though the draft GAP mentions the WHO CEWG Report it does not propose any action based on that report. The CEWG Report recommends open approaches to R&D and innovation, and not open collaboration. These two concepts are different. According to the CEWG, open approaches to R&D and innovation include competitive research platforms, open source and open access schemes. The CEWG defines open knowledge innovation as “research and innovation that generate knowledge which is free to use without legal or contractual restrictions and it includes open approaches to research and development and innovation…”
Open collaboration, unlike open knowledge innovation, does not necessarily make the R&D outcomes available to be used freely, and involves protection of intellectual property rights. It is more of a division of labor rather than open innovation.
Further, the draft GAP does not address the building of R&D capability and technology transfer in the context of R&D and innovation. The Global Strategy and Plan of Action on Public Health Innovation and Intellectual Property identifies as a key element the building of capability in developing countries to meet their health R&D needs.
The draft GAP refers three times to the issue of spurious/substandard/falsely- labeled/falsified/counterfeit (SSFFC) medicines and the ongoing Member State Mechanism process. Subsection 5.4.2 states: “implement recommendations of the Working Group of Member States on Substandard/Spurious/Falsely-labeled/Falsified/Counterfeit medical products to ensure oversight of the supply chain and prevent substandard, spurious, falsely-labeled, falsified, or counterfeit medicines reaching patients”. In fact there is no such working group established on this issue. There is a Member State Mechanism (MSM) and this process is yet to reach a shared understanding on the actions and conduct which lead to SSFFC. In the absence of such understanding reference to SSFFC in the draft GAP is equivalent to accommodating the pharmaceutical TNCs’ agenda of intellectual property enforcement in the context of antimicrobial medicines. Further there is no well-established independently verifiable evidence to link AMR with the circulation of SSFFC medicines.
The draft GAP does not use the word “quality” in a uniform manner. In part 3 on the action plan goals the draft uses “appropriate quality”. In subsection 5.2.1 it uses the word “agreed quality”. In subsection 5.4.1 it uses the word “good quality”. According to experts there is such term as good quality. There is only one term which is technically correct i.e. quality. Terms like “good quality” can facilitate the ratcheting up of regulatory standards and harmonization through the back door, which can hamper the local manufacturing capabilities of developing countries’ pharmaceutical industry.
While the draft GAP stresses the enhancement of quality standards one needs to be cautious about the ongoing conflict of interests in the quality and standard setting process of the WHO. WHO sits with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use(ICH), a standard setting platform promoted by pharmaceutical TNCs that critics say brings pro-industry standards through the backdoor as WHO guidelines.
(Set up in 1990, the ICH brings together the regulatory authorities and pharmaceutical industry of Europe, Japan and the United States “to discuss scientific and technical aspects of drug registration”. Its critics note that the ICH in effect is a mechanism for the pharmaceutical industry to influence, even set, standards. "Harmonization" in this context is a code word for industry-led standards setting which favours the interests of pharmaceutical TNCs in order to prevent generic medicines competition. For more details see: http://www.twn.my/title2/health.info/2014/hi140508.htm)
The draft GAP proposes the regulation and control of promotional practices of industry as an action by Member States under Strategic Objective 4 (“Optimize the use of antimicrobial medicines in human and animal health”). Similarly the Secretariat is to provide a leadership role in strengthening medicine regulatory system at national and regional levels, so that appropriate practices for optimizing use of antimicrobials are supported by appropriate and enforceable regulation, and that promotional practices can be adequately regulated. However, there is no reference to adherence to national and international regulation on the promotion of antimicrobial medicines. The WHO Global Strategy on the Containment of Antimicrobial Resistance (http://www.who.int/drugresistance/WHO_Global_Strategy_English.pdf) clearly calls for the adherence to national and international codes of practices on promotional activities. This clear language is missing in the draft GAP.
Another important omission is the explicit mention of promotion of rational use of antimicrobial medicines. Even though the WHA 67.25 explicitly refers to regulation and promotion of rational use of medicines, including in animal husbandry, and ensuring proper patient care, the draft GAP does not state this as a strategic goal or objective.
Lastly the draft GAP maintains a strategic silence on conflict of interests even though it proposes actions in collaboration with non-state actors in many places of the draft GAP.+