Transcript Overview on Medicines Regulation: regulatory cooperation and harmonization in the focus Dr Samvel Azatyan Manager, Medicines Regulatory Support Programme Quality Assurance and Safety: Medicines Essential Medicines.

Overview on Medicines Regulation:
regulatory cooperation and
harmonization in the focus
Dr Samvel Azatyan
Manager, Medicines Regulatory Support Programme
Quality Assurance and Safety: Medicines
Essential Medicines and Pharmaceutical Policies
World Health Organization
E-mail: [email protected]
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
1 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Why regulation of medicines is needed?
What is special with medicines, compared to other goods /
commodities?
 As a rule, patients are not able to make independent
judgement about of the QUALITY, SAFETY and EFFICACY;
─ Even health professionals have difficulties, unless they are
specially trained;
Medicines regulation is the totality of all measures - legal,
administrative and technical - which governments undertake
to ensure the quality, efficacy and safety of medicines, as
well as the relevance and accuracy of the product
information.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
2 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Why regulation of medicines is needed?
Consequences of under-regulation due
to the weak regulatory capacity
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irrational consumption and prescription;
quality of medicines is not assured - substandard,
counterfeit, harmful, useless medicines on the market.
Consequences of over- or improper regulation
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shortage of needed medicines or delayed access;
increased costs of medicines due to the cost of
regulatory system.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
3 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Rationale for Government's role
 Governments are obliged to intervene in the activities
of the pharmaceutical sector due to public health and
safety concerns;
 In this context, medicines regulation is a public policy
that restricts private sector activities in order to
attain social goals identified by the State;
Medicines regulation in the countries is performed
through National Medicines Regulatory Authorities
(NMRAs)
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
4 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Medicines regulatory authority
In a broad sense medicines regulatory authority means a
network (institution) that administers the full spectrum of
drug regulatory activities, including at least the following functions:
 Marketing authorization for new products and
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variation of existing authorizations;
GMP, GCP, GLP inspections;
Licensing and post-license control of manufacturers,
wholesalers and other distribution channels;
Quality control laboratory testing;
Adverse drug reaction monitoring;
Provision of drug information and promotion of
rational drug use;
Enforcement operations;
Monitoring of Drug Utilization, etc.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
5 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Main principles of medicines regulation –
although, not always observed..
Medicines regulation should:
 Have patient in the focus;
 Be evidence and science based;
 Be risk based;
 Bring added value;
 Respect interests of stakeholders and real possibilities;
 Be transparent but respect confidentiality;
 Be effective and flexible;
 Be part of broader overall pharmaceutical policy of the
country.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
6 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Main principles of medicines regulation –
although, not always observed..
…But also keep in mind, that:
 Regulations must be attuned not to the wishes, but to
available resources (technical, human, financial, etc.);
 Due to the complexity and resource constrains, the
requirements developed and successfully implemented
in one country may not be equally successful in
another country;
 … Attempts to apply more sophisticated requirements
may have (at least, in short term) serious public health
implications.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
7 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Differences in regulatory capacity globally
193 WHO Member States:
The reality is that many
regulatory authorities don't
have the full capacity to 20%
perform all regulatory
functions, due to chronic
shortages of human,
30%
technical, financial and
other resources
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
8 | 31 October - 4 November 2011, WHO Headquarters, Geneva
50%
Developed
Variable
Limited
Differences in regulatory capacity
in African Region
46 WHO Member States:
33%
24%
4%
39%
Source:
Developed
Moderate
Basic
Limited
WHO/AFRO/EDP/04.5: Availability of Drug Regulatory and Quality Assurance
Elements in Member States of the WHO African Region, 2004, Brazzaville.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
9 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Assessments of medicines regulatory systems in
26 sub-Saharan African countries
 Guidelines and assessment procedures are not
up to international standards and are often of an
administrative rather than technical nature;
 Wide-ranging exemption clauses not justified by
a risk assessment, for example for public sector
imports or donations;
 Scarce resources severely limited technical
assessment of dossiers;
 In spite of resource constraints few countries
relied on decisions made by other regulators
(such as stringent NMRAs or by the WHO
Prequalification Programme);
 Regulatory decisions by other competent
authorities were not widely recognized.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
10 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Critical issues in regulation of medicines
 Chronic shortages of resources;
 Different institutional arrangements existing for
the regulation of medicines in different settings;
 Expertise and capacity existing in different
NMRAs are different too..
 Even well-resourced regulatory authorities are not
anymore able and willing to carry the burden alone..
 There is a clear need for a new approaches in the
medicines regulation.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
11 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Main challenges in regulation
 Increasing difficulty for regulators to make fare balance
between potential risks involved with new medicines
and increasing public expectations for the safety of
medicines;
 Greater access to information and
demand for quality information;
 Increasing number of borderline
products with health claims;
 The gaps among regulatory
systems of WHO Member States
are rather increasing than
decreasing.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
12 | 31 October - 4 November 2011, WHO Headquarters, Geneva
"Innovative" approaches to cope with
increasing demands and limited resources
 Avoid doing things that do not give added value;
 Concentrate on things that do give added value;
 Pragmatically and focus on priority issues, which are
most relevant for public health (risk-benefit approach);
 Increase effectiveness of internal operations;
 Co-operate with partners in order to eliminate
duplicated activities;
 Share your work with others – do what you can do
better and let others to do what they can do better
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
13 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Prioritization of the regulatory activities
 Many NMRAs with limited resources may limit their scope
of activities to performance of those "core" regulatory
functions, which could potentially bring maximum added
value to the public health;
 Other regulatory functions could be more and more
shared with the colleagues in other NMRAs (especially in
the frameworks of existing RECs) and relying on the
opinions made and decisions taken by other regulators;
 This will allow WHO and other partners to prioritize the
support efforts and to introduce a system for accreditation
(or prequalification) of NMRAs for performance of specific
regulatory functions, in accordance with specific
international standards.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
14 | 31 October - 4 November 2011, WHO Headquarters, Geneva
More specific "innovative" (or heretic..)
approach
 Introduction of the concept of "levelling" for the
pharmaceutical products (essential medicines), according
to the "quality-related risk", into:
─ Low risk products
─ Medium risk products
─ High risk products
 This will create incentives and motivation for the
development, in case if NMRA wishes to "jump" a level
up, e.g., from regulation of low risk products to medium
risk products.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
15 | 31 October - 4 November 2011, WHO Headquarters, Geneva
What MRS is doing to support regulators
 Developing evidence - assessments of regulatory systems worldwide
(around 50 NMRAs assessed in all 6 regions);
 Providing direct technical support (capacity building, tools and
guidance) to regions and countries (with PQ and IVB);
 Stimulating / initiating collaboration between regulators from various
countries on various regulatory activities (from "North → South" to
"South ↔ South");
 Facilitating the establishment
of "Centres of excellence"
for regulatory affairs;
 Promoting harmonization.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
16 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Collaboration with other Programmes and
Units within EMP and outside
HSS/EMP
FCH/IVB
QSM (PQ, Safety)
QSM (Quality
Assurance)
QSM (Blood products)
MAR (GGM)
QSS
(Regulatory pathways)
Disease-oriented
programmes
HTM/GMP
(Global Malaria
Programme)
Other Programmes
Medicines Regulatory Support
WHO Regional Offices
WHO Country Offices
National Medicines Regulatory Authorities
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
17 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Faster access to medicines through
sharing of regulatory information
 MRS is working with regulators to find out how best to
build confidence in regulatory decisions taken by other
regulators, including:
─ how to facilitate exchange
of consolidated information
about assessments and
inspections;
─ without challenging their
sovereignty.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
18 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Sharing of expertise vs. recognition of
decision
Acceptance of expertise is not equal to acceptance
of decision:
 Acceptance of expertise
– is sovereign and complex regulatory decision of NRA based on
scientific arguments and confidence;
– may be applied case to case;
– is followed by formal independent decision according to national
legislation and mandate of national MRA;
 Acceptance of decision
– is a formal legal act, frequently requiring international treaties;
– may modify liabilities of involved parties and requires legal
specification of acceptance and non-acceptance.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
19 | 31 October - 4 November 2011, WHO Headquarters, Geneva
New regulatory approaches
Smaller or less resourced regulatory authorities more and
more starting to rely on the approvals or opinions issued by the
well-resourced regulatory authorities
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Examples of this type of initiatives include, but are not
limited to:
WHO PQP - HIV/AIDS, TB, malaria, RH, paediatric therapy;
US PEPFAR - HIV/AIDS;
EU Article 58 – assessment of products for use outside the
European Union territory;
Canada's Access to Medicines Regime – assessment of
products according to WHO Model List of Essential Medicines;
Other – orphan medicines, paediatric medicines.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
20 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Regulatory harmonization
In a broad sense harmonization means harmonization
of technical requirements for medicines regulation,
i.e., legislations, guidelines, procedures, etc.
 These requirements relate to the quality, safety and
efficacy of the medicinal products;
 These requirements differ in complexity, from one type
of marketing authorization application to another;
 To start with innovators or with generics? Or both?
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
21 | 31 October - 4 November 2011, WHO Headquarters, Geneva
What we do mean under Harmonization?
 True harmonization goes further than just development
of common documentation;
 It requires effective communication and collaboration
aimed at building capacity and trust (e.g.,
information sharing, recognition and joint working);
 In combination, these activities can lead to similar or
collaborative approaches to drug registration;
 Paving the way for mutual recognition and/or
centralized registration (if desired) in the longer-term
future.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
22 | 31 October - 4 November 2011, WHO Headquarters, Geneva
What we do not mean under Harmonization?
Harmonization doesn't mean a loss of national sovereignty / autonomy
(and certainly not in the early stages)
 Common documentation stipulates the requirements for registration;
 Better communication enables countries to chose which information
they will use;
 Collaborative mechanisms, such as joint assessments or inspections,
does not imply collaborative decision-making!
In all cases the registration decision itself
stays firmly in the hands of sovereign nations
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
23 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Scope and objectives for harmonization
 Objective of drug regulation:
TO IMPROVE AND PROMOTE PUBLIC HEALTH
 In case harmonization is supported by International
Community – main objective should be:
►
MEASURABLE PUBLIC HEALTH GAINS
 There may be other gains, but these should be in the
centre.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
24 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Potential public health gains from
harmonization
 Less risk of being harmed by medicines (safety risks
combined with no treatment effect risks) as gradual
improvement of quality, safety and efficacy of products
on the markets is expected;
 More rapid access to needed medicines (high priority
essential medicines, new medicines…);
 Better value for money (both for out of pocket and
public funds), as no waste on substandard and of poorquality medicines;
 Increasing trust in generic medicines (also better value
for money).
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
25 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Potential gains have to be balanced with…
potential losses
 Increased price level of medicines (quality has its
price);
 Reduced access – not all medicines on the market
may meet new harmonized standards;
 Increasing price for medicines regulation
(harmonization has its price too);
 Local industry may not always win;
 Wholesale and retail businesses may loose many of
the products that were bestsellers for them.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
26 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Potential scope for harmonization in Africa
 Harmonization of technical requirements
– Generic drugs vs NCEs – move from generics to NCEs
– Priorities (CTD, modules for generics, GMP), timeframes and
working methods for creation of guidelines to be determined;
 Implementation of harmonized technical requirements;
 Establishing for priority products a special pathway –
one set of assessments/inspections – access to all
markets
– Either via "centralized procedure" (one application, one
process and one result for all) or "mutual recognition" (same
application for all or some, one MRA does the job and others
recognize without duplication).
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
27 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Regulatory harmonization in Africa
 Africa – a continent of
huge diversity and
complex unity, with
numerous Regional
Economic Communities
(REC);
 … overlaps and
politically complicated
environment.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
28 | 31 October - 4 November 2011, WHO Headquarters, Geneva
African Medicines Registration
Harmonization Initiative (AMRHI)
 Process started with the informal
consultations in ICDRA Meeting,
September 2008, Bern, Switzerland;
 In response to the growing
recognition of the potential benefits of
harmonizing medicines registration in
Africa, a WHO concept paper was
developed to describe a proposed
approach to supporting drug
registration harmonization within and
across African regional groupings.
WHO Drug Information, Volume 22,
Number 3, 2008
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
29 | 31 October - 4 November 2011, WHO Headquarters, Geneva
African Medicines Registration
Harmonization Initiative (AMRHI)
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Further discussions and orientation in the meeting in
Johannesburg, South Africa, 24-26 February 2009, organized
jointly by BMGF, NEPAD, William J. Clinton Foundation and the
WHO.
The purpose of the meeting was:
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to explore the possibilities of supporting medicine registration
harmonization, as an initial first step to broader regulatory
harmonization within African Regional Economic Communities
(RECs) and organizations, and
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to initiate a strategic approach to develop project proposals for
mobilizing the necessary financial and technical resources to
support RECs undertaking medicine registration harmonization.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
30 | 31 October - 4 November 2011, WHO Headquarters, Geneva
African Medicines Registration
Harmonization Initiative (AMRHI)
 Donor partners, NEPAD and WHO confirmed their interest in
supporting the RECs, including necessary actions to support
national implementation, strengthen national regulatory
agencies and promote inter-REC and continental exchange of
information, coordination and technical consistency.
 Their strategic approach was to invite summary project
proposals (SPPs) from committed RECs and seek financial
and technical support for the most sound and promising
proposals among them.
 Several RECs have submitted their SPPs and at this stage one
of them has been approverd – East African Community
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
31 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Conclusions
 Medicines regulation is not anymore a "single-player"
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activity;
Prioritization of regulatory activities, work sharing and
collaboration can help reduce workload and improve
public health by improving overall regulatory
performance.
It can help to direct the expert knowledge and resources
to performance of the functions that can improve public
health and facilitate access to essential medicines;
Formation of effective networks between regulatory
authorities nationally and internationally may facilitate
sharing of scarce resources and eliminate duplicating of
activities.
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
32 | 31 October - 4 November 2011, WHO Headquarters, Geneva
Thank you!
Photo by:
www.buildmyaudience.com
www.who.int/medicines
[email protected]
WHO/UNICEF Technical Briefing Seminar on Essential Medicines Policies,
33 | 31 October - 4 November 2011, WHO Headquarters, Geneva