Dr Samvel Azatyan Manager, Medicines Regulatory Support Programme

Overview on Medicines Regulation: regulatory cooperation and harmonization in the focus Dr Samvel Azatyan Manager, Medicines Regulatory Support Programme Quality Assurance and Safety: MedicinesEssentialMedicines and Pharmaceutical PoliciesWorld Health OrganizationE-mail: azatyans@who.int

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.

Why regulation of medicines is needed? Consequences of under-regulation due to the weak regulatory capacity • irrational consumption and prescription; • quality of medicines is not assured - substandard, counterfeit, harmful, useless medicines on the market. Consequences of over- or improper regulation • shortage of needed medicines or delayed access; • increased costs of medicines due to the cost of regulatory system.

Rationale for Government's role • Governments are obligedto 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 activitiesin order to attain social goals identified by the State; Medicines regulation in the countries is performed through National Medicines Regulatory Authorities (NMRAs)

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 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.

Main principles of medicines regulation Medicines regulation should: • Have patientin the focus; • Be evidence based; • Be risk oriented; • 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.

Main principles of medicines regulation …But also keep in mind, that: • Regulations must be attuned 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; • The application of more sophisticated requirements may have (at least, in short term) serious public health implications.

Differences in regulatory capacity globally 193 WHO Member States: For different reasons, many regulatory authorities do not have the full capacity to perform all regulatory functions.

Differences in regulatory capacity in African Region 46 WHO Member States: Source:WHO/AFRO/EDP/04.5: Availability of Drug Regulatory and Quality Assurance Elements in Member States of the WHO African Region, 2004, Brazzaville.

Critical issues in regulation of medicines • Not all regulatory functions are performed due to chronic shortages of human, technical and financial resources; • Different institutional arrangements exist for the regulation of medicines: Weak regulatory frameworks and lack of enforcement can lead to various bottlenecks limiting access to essential medicines. • Regulators are perceived as an additional "road-block" to access to new therapies..;

Strategies to cope with increasing demands • Avoid doing things that do not give added value; • Concentrate on things that do give added value; • Be pragmatic and focus on priority issues, most relevant for public health (risk-benefit approach); • Increased effectiveness of internal operations • Quality systems, international benchmarking; • Co-operation with partners in order to increase regulatory capacity by elimination of duplicated activities • Facilitated by comparable standards and administrative requirements.

WHO approaches for regulatory support • 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"); • Promoting harmonization.

Collaboration of MRS Programme with other Programmes and Units within EMP and outside HSS/EMP QSM (PQ, Safety) QSM (Quality Assurance) QSM (Blood products) MAR (GGM) FCH/IVB 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

Faster access to medicines throughsharing 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. "You kids share your food and stop being shellfish!"

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.

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 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.

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.

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.

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

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 poor-quality medicines; • Increasing trust in generic medicines (also better value for money).

But… 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.

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).

Regulatory harmonization in Africa • Africa – a continent of huge diversity and complex unity, with numerous Regional Economic Communities (REC); • … overlaps and politically complicated environment.

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

African Medicines Registration Harmonization Initiative (AMRHI) • 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: • 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 • to initiate a strategic approach to develop project proposals for mobilizing the necessary financial and technical resources to support RECs undertaking medicine registration harmonization.

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 from committed RECs and seek financial and technical support for the most sound and promising proposals among them.

African Medicines Registration Harmonization Initiative (AMRHI) next steps for further implementation of the project: • By 31st May 2009 RECs were invited to submit to WHO and NEPAD a summary project proposal in support of regional medicine registration harmonization. A draft format and a suggested scope and outline are available. NEPAD and WHO are willing to give limited technical support to the development of such regional proposals. • April - May 2009: Submission of summary project proposals; • June 2009: Review of proposals and feedback to RECs; • July - October 2009: Selected RECs to submit their full project proposals to NEPAD & WHO; • November-December 2009: Review of full project proposals by Project consortium and submission to interested Donors; • January - June 2010: Expected start of the implementation of first approved projects. • …..

Conclusions • Sharing of information, collaboration and harmonization can help reduce workload and improve 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; • Harmonization may contribute in building regulatory capacity and trust, which is an important achievement in its own right.

Thank you! www.who.int/medicines mrsmail@who.int Photo by: www.buildmyaudience.com

Dr Samvel Azatyan Manager, Medicines Regulatory Support Programme