Info Service on Health Issues (May14/02)
20 May 2014
Third World Network
WHO: Alliance with
industry raises concerns over medicine regulation
Published in SUNS #7807 dated 20 May 2014
Geneva, 19 May (K. M. Gopakumar) -- There are concerns that the World
Health Organisation (WHO)'s alliance with an industry-led body facilitates
regulatory capture of medicine regulation by pharmaceutical multinational
A recent news report brought out the conflict of interest involved
in the WHO's norms and standard-setting related to medicines due to
the involvement of the International Conference on Harmonisation of
Technical Requirements for Registration of Pharmaceuticals for Human
The article provides further details of the deep-rooted conflict of
interest and regulatory capture through the WHO-ICH alliance. This
"unholy alliance" with ICH is expected to come up during
the World Health Assembly (WHA), which started its current annual
session in Geneva on Monday.
A draft resolution titled "Regulatory System Strengthening for
the Medical Products" urges Member States to implement the ICH
The resolution refers to "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
The text is currently in brackets, signifying lack of consensus among
WHO member countries, and enjoys the full support of developed countries,
especially the European Union.
However, Third World Network learnt that the United States is negotiating
with the EU to remove the explicit reference to ICH.
The proposal is to remove reference to ICH but to retain words such
as harmonisation and to push for regulatory harmonisation (read as
ratcheting up of regulatory standards suited for pharmaceutical MNCs).
The WHO-ICH alliance also casts doubt on the effectiveness of WHO's
framework for engagement with the private sector.
The current WHA session is expected to take a decision on whether
to adopt the draft framework for Non-State Actors (NSAs), which includes
a draft policy for engagement with the private sector.
The Draft NSA policy states that: "WHO's processes in setting
norms and standards must be protected from any undue influence".
Further, the policy proposes the exclusion of NSAs from participating
in the process of setting policies or norms. It also prevents the
acceptance of resources for normative work.
Thus, the participation of WHO is contrary to the proposed draft policy
on engagement with NSAs, which sets a boundary for such engagement.
However, in order to create room for participation of the private
sector, especially initiatives like ICH norm-setting activities, the
policy divides the norm-setting activities into three phases viz.
Phase 1: Information gathering; Phase 2: Preparation for, elaboration
of and decision on the normative text; and Phase 3: Implementation.
It further states that reference to specific protection of the norms
and standard-setting process refers to the second phase.
Thus, the draft policy creates room for the participation of the private
sector in the early phase of norm-setting activities, in the form
of information gathering.
The very participation of WHO in ICH activities de facto legitimises
guidelines developed by the pharmaceutical multinational industrial
association and developed country regulators together, with a primary
objective of serving the interest of pharmaceutical MNCs.
Apart from this push for formal adoption of ICH guidelines, WHO has
facilitated the backdoor entry of ICH guidelines into WHO's various
guidelines adopted through the WHO's Expert Committee on Specifications
for Pharmaceutical Substances (Expert Committee).
The Regulatory System Strengthening (RSS) resolution is an attempt
to formally legitimise an alliance, which contradicts the neutrality
of norm-setting and allows regulatory capture.
The WHO-ICH alliance is problematic in terms of the process as well
as content. Apart from the concerns on the implication of ICH outcomes
to affordability of medicines, it raises concerns on the neutrality
and evidence-based decision-making, along with issues of participation
and transparency in WHO's decision-making.
The implication on affordability of medicines is discussed below.
The ICH was established in 1990 as a public-private partnership (PPP)
primarily to lower down the norms of registration (marketing approval)
of new chemical entities. However, as shown below, increasingly the
ICH started setting standards to build a set of technical barriers
to prevent competition from the generic industry.
The founding members of ICH are the drug regulatory authorities of
the EU (European Agency for the Evaluation of Medicinal Products,
EMEA), Japan (Ministry of Health, Labour and Welfare, JMHLW), and
the US (Food and Drug Administration, US FDA) and the research-based
pharmaceutical industry associations of those countries (the European
Federation of Pharmaceutical Industries' Associations, EFPIA; the
Japan Pharmaceutical Manufacturers Association, JPMA; and the Pharmaceutical
Research and Manufacturers of America, PhRMA).
These founding members along with the International Federation of
Pharmaceutical Manufacturers Associations (IFPMA), a federation of
national associations of research-based pharmaceutical industry associations,
WHO, Health Canada (Canadian regulatory agency), and the European
Free Trade Area constitute the highest decision-making body of ICH,
the steering committee.
However, only the steering committee members enjoy voting rights and
the other four members including WHO have no voting rights. The ICH
secretariat operates out of the Geneva office of IFPMA.
According to the ICH website, since its establishment in 1990, each
of its six co-sponsors (EMEA, EFPIA, JMHLW, JPMA, US FDA, and PhRMA)
has had two seats on the steering committee. Other parties have a
significant interest in ICH and have been invited to nominate observers
to the committee.
According to researcher Stephanie Dagron: "The steering Committee
oversees all activities. First, it determines the harmonization activities
to be pursued (i. e. initiative for guidelines and other instruments).
Second, it adopts the guidelines and instruments that have been finalized
and accepted by the parties through consensus. Third, it supervises
the implementation and monitoring of ICH commitments. The IFPMA exercises
an important role since it provides the secretariat and participates..."
There is an effort to reach out and co-opt ICH-established Global
Cooperation Groups (GCG).
GCG includes Regional Harmonisation Initiatives (RHIs) namely, APEC,
ASEAN, EAC, GCC, PANDRH and SADC, in addition to eight Drug Regulatory
Authorities/Departments of Health (DRAs/DoH) in Australia, Brazil,
China, Chinese Taipei, India, Republic of Korea, Russia and Singapore
that are invited to the ICH bi-annual meetings.
RHI/DRA/DoH representatives participate in the Global Cooperation
session of the ICH Steering Committee to discuss capacity-building
and share experience/challenges on the implementation of ICH Guidelines.
Dragon notes: "In 1999 the ICH-SC created the Global Cooperation
group as a subcommittee, to allow the ‘participation' of representatives
from non-ICH regions. In 2008, the ICH (steering committee) also created
a structure called the Regulators Forum. But these two structures
do not offer any participation opportunities to their members within
the elaboration process of the ICH guidelines. They only constitute
platforms for discussion, information, and training. Their role is
to allow the dissemination of ICH standards worldwide".
According to the ICH website, representatives also listen to ICH technical
topics discussed by the steering committee during meetings and are
invited to nominate technical experts in Expert Working Groups/Implementation
Working Groups to contribute to the development of ICH Guidelines.
However, participation in the GCG is without any substantial say,
without voting rights.
Industry representatives act as one of the coordinators as well as
in the working group. The role of WHO is not limited merely to an
observer to ICH. It actively participates in the ICH Expert Working
The ICH, during the last 24 years, has worked as a partnership between
the regulatory agencies of industrialised countries and pharmaceutical
industry without any effective participation from developing countries
and generic industries.
However, the important question is how regulatory agencies and WHO
set norms in a body where the industry has a veto power through voting?
Thanks to the alliance with WHO, many ICH guidelines found a place
in the Report of WHO's Expert Committee on Specifications for Pharmaceutical
In other words, the norms and standards set by ICH without the participation
of a substantial majority of Member States got imported to the WHO
Expert Committee process and adopted as norms and standards for the
regulation of medicines.
For instance, the Pharmaceutical Development of Multisource (generic)
Pharmaceutical Products contained in the 46th Report of the Expert
Committee states that "... document provides a structured approach
for industry following the International Conference on Harmonisation
(ICH) common technical document (CTD) format".
The 44th Report of the WHO Expert Committee also contains WHO Good
Manufacturing Practices for Active Pharmaceutical Ingredients (API),
which are based on the ICH guidelines.
It states: "A major change to the analytical procedure, or in
the composition of the product tested, or in the synthesis of the
API, will require re-validation of the analytical procedure. Note:
Further guidance on validation of analytical procedures is available
in the following: Guideline elaborated by the International Conference
on Harmonisation of Technical Requirements for Registration of Pharmaceuticals
for Human Use (ICH)".
The ICH and IFPMA participate at the meetings of the WHO Expert Committee
on Specifications on Pharmaceutical Substances.
Researchers also question the ICH claims that its guidelines are purely
science-based. They point out that commercial and political interests
play an important role in the finalisation of ICH guidelines.
A set of research papers shows that ICH served the pharmaceutical
MNCs' interest in two ways.
First, it set norms to lower the threshold level of technical requirements
for the registration of medicines containing new chemical entities
and new products obtained by biotechnology through harmonising the
drug registration process.
Second, ICH started setting norms and standards for generic products
and pharmaceutical substances (starting materials) and created a new
entry barrier for small brand name and generic companies, especially
those in developing countries.
Health researchers even warn against the drive on harmonisation.
In an article, Karin Timmermans writes: "... increasing the standards
beyond the technological capacity of pharmaceutical companies in developing
countries would effectively exclude their competitive, generic products
from the international market".
Another researcher warns that: "The production of generics but
also of pharmaceutical starting material in developing countries is
endangered. In fact, ICH guidelines have introduced a tightening of
specifications for pharmaceutical starting materials, which is not
always justified by additional safety benefits. Another source of
prohibitive costs for smaller companies is the Good Manufacturing
Practice Guide for active pharmaceutical ingredients adopted by ICH
The same sentiment is expressed by an expert consultation organised
by WHO in 2001.
The experts state: "ICH has relied increasingly on advanced pharmaceutical
technology in its standard setting, on the assumption that this technology
will lead to greater safety of new drugs, while the ICH guidelines
relating to drug quality have introduced a general tightening of specifications
for pharmaceutical starting materials. For example, ICH guideline
Q3A ("Impurities in new drug substances") includes the requirement
that each organic impurity (whether identified or unidentified) present
in a substance in the amount of 0.1% or more (in some cases 0.05%
or more) should be considered as a qualified impurity (i. e. its safety
should be established). This raises the question of the basis for
the selection of the borderline figure, as the additional safety benefits
from these rigorous standards have not been demonstrated but the costs
incurred by manufacturers in meeting the requirements are significant."
Further, the experts warn against making ICH norms as global standards.
The report states: "Setting such norms may have considerable
repercussions on current manufacturing practices, as only pharmaceutical
companies with substantial resources can achieve the necessary standards.
This is a concern if the guidelines are intended for global application.
Smaller pharmaceutical companies, generic companies and many larger
companies responsible for essential drug production in developing
countries may be effectively squeezed out of drug manufacturing if
ICH guidelines start to be interpreted as the only global standard."
However, the experts recommended to continue WHO's engagement with
The report states: "WHO attends meetings of the ICH Steering
Committee and the Global Cooperation Group as an observer. These roles
are important and should be maintained. However, appropriate strategies
for consultation and communication with Member States need to be developed
to ensure that WHO is not seen as de facto automatically endorsing
ICH products, but as providing advice on the potential impact of those
products on non-ICH Member States."
The WHO has continued with the ICH process for more than 24 years
without the close scrutiny of Member States because the issues of
norms and standards are considered as technical subjects; therefore,
the World Health Assembly never deliberates the merits of the Expert
Committee Reports, which contain norms and standards for the regulation
The Report of the Expert Working Group is placed before the WHA Executive
Board to take note of the Report along with many other expert reports.
Normally, the Executive Board takes note of expert reports without
The ICH adopts guidelines with political and economic considerations
and successfully projects these guidelines as science-based and exported
to WHO Expert Committees. The WHO's alliance with ICH facilitates
In the past, Member States had forced WHO to discontinue its engagement
with the International Medical Product Anti-Counterfeit Task Force
(IMPACT) due to its close association with the pharmaceutical industry.
The challenge at this point is for Member States to scrutinise WHO's
alliance with ICH and prevent any further conflict-of-interest situations.