Info Service on Health Issues (May14/08)
Geneva, 30 May (K M Gopakumar) – Pharmaceutical influence over medical product regulation at the World Health Organization has been pushed back by governments.
The 67th World Health Assembly (WHA) that took place on 19 – 24 May adopted the resolution on regulatory system strengthening for medical products after dropping reference to regulatory harmonisation and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Set up in 1990, the ICH brings together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US “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 transnational corporations in order to prevent generic medicines competition.
resolution was proposed at the 134th meeting of WHO Executive Board,
which took place 20-25 January 2014 in Geneva. See http://apps.who.int/gb/ebwha/pdf_files/EB134/B134_R17-en.pdf
There was no consensus at the Executive Board due to concerns from some developing countries and the draft resolution was forwarded with bracketed text to the WHA for health ministers to resolve.
Developing countries such as India and China continued to express concern at the WHA on harmonisation and reference to the ICH. India stated that their support for the resolution is based on a common understanding that the development of norms, standards or guidelines as per WHO principles, are free from conflict of interest and excludes the influence from any initiative driven by industry. China stressed national autonomy and independence in regulatory cooperation, and that harmonization should be on a voluntary basis.
The removal of the words “harmonization and convergence” from the text of the resolution that was finally adopted clearly shows that there is a consensus among Member States to accept the concerns over regulatory harmonization. Secondly, Member States clearly expressed concerns with regard to the involvement of industry in the WHO’s regulatory norms and standard setting.
The draft resolution that was brought to the WHA from the Executive Board, in Operational Paragraph 1(f), urged Member States to “implement relevant guidance and science-based outputs of international regulatory harmonization and convergence efforts such as, where applicable, the Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.”
It further urged Member States to promote international cooperation to promote “convergence” (an indirect reference to harmonisation) in Operational Paragraph 1(3).
In Operational Paragraph 2(1) the resolution requested the WHO Director General to develop appropriate norms and standards, “taking into account the standards created by existing regional and international initiatives”. Further, it also asked the WHO DG to promote the greater participation of Member States in existing international and regional initiatives for collaboration, harmonization and convergence in accordance with WHO principles and guidelines.
Four days of informal negotiations at the recently concluded WHA led to the finalisation of the resolution.
The resolution is believed to be an effort to further Global Medicines Regulatory Harmonisation (GMRH), an initiative by the World Bank. The World Bank is administering a multi-donor trust fund, which was established in 2011 with an initial contribution of USD 12.5 million from the Bill & Melinda Gates Foundation (Gates Foundation).
According to the annual report of GMRH published in 2013 the origins of the initiative goes back to 2009. According to this annual report “In 2009, a consortium of partners including the Pan African Parliament, NEPAD Agency, the World Health Organization, Bill & Melinda Gates Foundation, UK Department for International Development, and the Clinton Health Access Initiative came together to establish the African Medicines Regulatory Harmonization (AMRH) Program”. With the help of Gates Foundation funding “it possible for the World Bank to set up GMRH to implement AMRH and to scale up medicines regulatory harmonization activities in Africa and beyond.”
US Food and Drug Administration (USFDA) and International Conference
on Harmonisation of Technical Requirements are believed to be important
partners. See http://www.who.int/medicines/areas/policy/IPC_dec2012_Seiter_reg.pdf
According to a paper by Aylet Berman, a researcher who has worked extensively on the ICH, the ICH standards “have been to the detriment of entities, companies and countries that lack sufficient resources, and have advantaged resourceful companies and countries. In practice, this means that they have benefited larger, privately held, export-oriented companies, and have been to the detriment of smaller, locally oriented, or governmentally funded companies/entities”.
She further states “in certain contexts, they have promoted the commercial interests of the multinational pharmaceutical industry over the interests of patients in receiving much needed medicines or treatments”. According to her “the members are the main beneficiaries, non-members have been subject to distributional effects that are to their detriment”.
WHO’s involvement in ICH activities raises serious concerns on conflict of interest with regard to WHO’s role in the norms and standard setting related to medicines (See TWN Info Service mailing dated 19 May 2014: “WHO alliance with industry raises concerns over medicine regulation”.)
The adopted resolution amended the preamble paragraph of the version from the Executive Board that contained a reference to ICH. The preamble originally stated: “Also noting with appreciation the ongoing collaboration between some national regulatory authorities, including at the global level, in setting standards, including the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use among others, and encouraging a continued emphasis of effort in strengthening regulatory systems in accordance with WHO principles and guidelines”. The amended preamble reads” “noting the ongoing collaboration between national and regional promoting cooperation among authorities at the regional and global level”.
Operational Paragraph 1 (f) was also amended, which originally urges Member States to strengthen national regulatory systems by, as appropriate, “implementing relevant guidance and science-based outputs of international regulatory harmonization and convergence efforts such as, where applicable, the Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use”.
The resolution dropped the words “regulatory harmonization and convergence efforts such as, where applicable, the Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use the reference to harmonisation”. The amended text urges Member States to strengthen national regulatory systems, including through, as appropriate and voluntarily by “facilitating the use of relevant guidelines and science based outputs of WHO Expert Committee and good regulatory practices at the national, regional and international level”.
Similarly the word “convergence” was removed from Operational Paragraph 9 of the Executive Board version that originally stated: “to identify the need to strengthen regulatory system capacity, collaboration and convergence in the technically complex areas where substantial gaps may still exist, such as the regulation of biotherapeutic products, blood products, and in vitro diagnostics”. This is now renumbered in the final resolution as paragraph 10 without the word “convergence”.
In paragraph 2(1) the indirect reference to ICH has been removed. The earlier draft requested the WHO DG to continue to support countries in the area of regulatory system strengthening, including by developing appropriate norms and standards taking into account the standards created by existing regional and international initiatives …” This is now reflected as new text in Operational Paragraph 2 (2) that states: “to continue to develop appropriate norms, standards and guidelines, including taking into account national, regional and international needs and initiatives in accordance with WHO principles”.
The words “harmonisation and convergence” were removed from the draft paragraph 2(4) which originally stated: “to promote the greater participation of Member States in existing international and regional initiatives for collaboration, harmonization and convergence in accordance with WHO principles and guidelines”. The amended text now placed as paragraph 2(5) states: “to promote the greater participation of Member States in existing international and regional initiatives for collaboration, cooperation in accordance with WHO principles and guidelines”.
Similarly, paragraph 2(6) of the Executive Board version was also amended, removing the words “harmonisation and convergence”. The draft text read: “to increase support for and recognition of the significant role of the International Conference of Drug Regulatory Authorities in promoting the exchange of information and collaborative approaches among drug regulatory authorities, and as a resource to guide and facilitate further development of, and regulatory harmonization and convergence among, these authorities …”
The amended version clearly states “to increase support for and recognition of the significant role of the International Conference of Drug Regulatory Authorities in promoting the exchange of information and collaborative approaches among drug regulatory authorities, and as a resource to facilitate further development of, regulatory cooperation and coherence”.
Even though the resolution removed the reference to ICH and harmonization, we have yet to see whether the WHO Secretariat will bring any concrete changes in its approach to regulatory harmonization, taking into consideration the concerns expressed by Member States including India and China.
Skeptics are of the view that without constant monitoring by Member States the Secretariat is not going to change its approach. Even though the Assistant Direct General in charge of medical product regulation stated in a side event that the focus is on convergence and not in harmonization, observers point out that it is different words with the same meaning.
Concerned observers cite the Secretariat report to the WHA on RSS which clearly advocates regulatory harmonization. It states “In order to improve the regulation of medical products globally and ensure that the medical products that patients use are of assured quality, more emphasis needs to be placed on regulatory convergence and harmonization, which offers numerous benefits to both regulatory authorities and the pharmaceutical industry, and which has a positive impact for the protection of public health. Stimulating and/or initiating collaboration between regulators from various countries on regulatory activities based on converging and harmonized technical standards is becoming more and more important”.
Another reason for the Secretariat’s reluctance to move away from the harmonisation is emanating from WHO’s involvement in various harmonisation initiatives including at the international level (ICH and GMRH) and the regional initiatives like the Pan American Network for Drug Regulatory Harmonization and African Medicines Regulatory Harmonization Initiative.
Further, some observers also point out to the fact that even though the words harmonization, convergence and ICH have been removed from the resolution, there are still indirect references to ICH and harmonization efforts. This may be used by the Secretariat to justify its current engagement with ICH and other harmonization initiatives that may be problematic.
For instance paragraph 1(f) asks countries to facilitate, as appropriate and voluntarily, the use of relevant guidance of WHO experts committees along with good practices at the national, regional and international level. The words “international level” may be used to justify the ongoing engagement with ICH and other harmonization initiatives. Similarly, paragraph 2 (2) requests the DG while developing appropriate norms standards and guidelines to take into account international needs and initiatives in accordance with WHO principles. Again the Secretariat can justify its current approach citing the mandate under this paragraph which allows the DG to take into account international initiatives.
Yet again, paragraph 2(5) requests the DG to promote greater participation of Member States in the existing regional or international initiatives. Does this mean that WHO promotes the participation of Member States in various medical product regulatory harmonization initiatives, including the World Bank’s Global Medicines Regulatory Harmonisation?
However, it may not be so easy for the Secretariat to push for harmonization and to continue its current level of engagement with ICH. Operational paragraph 2(2) does not provide a blanket mandate to the Secretariat to engage with ALL international initiatives. The DG is to ensure that while taking into account of international initiatives it should be in accordance with WHO principles. As per the established WHO principles there should not be any engagement with industry in norms and standard setting. The ICH engagement is widely seen as in conflict with WHO principles due to a conflict of interest between industry and the WHO.
Member States who are concerned about the Secretariat’s activities in the area of regulatory system strengthening also have the opportunity of “gate keeping” to a certain extent through the Member State Mechanism. Operational Paragraph 2 (11) of the resolution requests the DG “to ensure that any activities carried out under this resolution does not duplicate or circumvent the work plan and mandate of the Member States Mechanism on SSFFC Medical products”. The Member State Mechanism identified strengthening of drug regulatory authorities as a priority in its work plan.
(SSFFC means “Substandard/spurious/falsely-labelled/falsified/ counterfeit medical products” in WHO parlance.)
The removal of the words “harmonization and convergence” from the resolution clearly reflects the consensus among Member States to accept the concerns over regulatory harmonization and the ICH as well as over the involvement of industry in WHO’s regulatory norms and standard setting. The translation of the resolution into action now depends on the constant vigilance of the Member States.
Further, the resolution also amended Operational Paragraph 1(8) which deals with prequalification of medical products. Prequalification is an evaluation of the WHO to assess the quality of medical products to facilitate the procurement of these products by international agencies such as UNICEF and the Global Fund for the treatment of HIV/AIDS, TB and Malaria. The Executive Board draft resolution stated: “to support WHO in its efforts to strengthen its prequalification programmes, including exploring modalities in consultation with Member States for improved sustainability of this critical programme, while also focusing on supporting national and regional initiatives to improve regulatory capacity for medical products focusing on achieving longer term objectives of developing national regulatory authority capacity among Member States.” This is now split into two separate operational paragraphs.
Operational Paragraph 8 now reads: “National and regional initiatives of regulatory authorities to improve regulatory capacities for review of medical products and to promote WHO’s long term objective of supporting the strengthening of national regulatory authority capacity among Member States.”
An additional Operational Paragraph 9 was added, which states: “to support WHO’s prequalification programmes, including exploring modalities in consultation with Member States for improved sustainability of these critical programmes”.
Similarly, Operational Paragraph 5 of the Executive Board version is amended to strengthen the integration and coherence among WHO’s prequalification programmes as an aid to assuring safe supply of quality medical products, engaging with Member States in the further refinement and improvement of the global prequalification model, while in parallel supporting the development of functional national and regional regulatory bodies and networks, leading to more global participation in the global prequalification programme.
The amended paragraph 5 is renumbered as Operational Paragraph 6 which states: “WHO’s prequalification including their integration and coherence, taking into account the needs and capacities of national and regional regulatory systems to assist in ensuring a supply of quality, safe, efficacious and affordable medical products.”
There are concerns with regard to strengthening and mainstreaming of WHO prequalification programmes without a complementing international procurement mechanism. In the absence of an international procurement mechanism, such mainstreaming of WHO’s prequalification as the stamp for quality assurance would affect local production initiatives and reduces the competition from generic producers. The resolution has thus put speed breakers in mainstreaming of WHO’s prequalification mechanism to assess the quality, safety and efficacy of medical products.
Finally one of the important weaknesses in the resolution is that it focuses only on one aspect of regulation and it is silent on other aspects the regulation viz. controlling the promotion and advertising of medical products; monitoring adverse reactions to medicines and medical products; providing independent information on medicines to professionals and the public. Even though the Secretariat’s report on regulatory system strengthening lists the above aspects as part of the regulatory mechanism, the resolution failed to include them. Similarly, it is also silent on the promotion of rational use of medicines. Thus the narrow focus on only certain aspects of regulation of medical products results in the lack of a holistic approach on regulation.+
(Note: This is an expanded version of the article first published in south-north development monitor SUNS #7814.)