1 |1 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Dr Samvel Azatyan Group Lead Capacity Building and Harmonization Support Regulatory Systems Strengthening [RSS] Regulation of Medicines and Other Health Technologies [RHT] Department of Essential Medicines and Health Products [EMP] World Health Organization Capacity building and technical assistance to regulators; Regulatory cooperation and harmonization initiatives

2 |2 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Why regulating medicines (1)  In most cases, consumers are not in a position to make decisions about when to use medicines, which medicines to use, how to use them and to weigh potential benefits against risks as, by definition, no medicine is completely safe.  Even healthcare professionals (medical doctors, pharmacists) sometimes have difficulties to take informed decisions about all aspects of medicines, unless they are specially trained.

3 |3 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Why regulating medicines (2)  Consequences of the use of ineffective, poor quality, harmful medicines, public health and safety concerns have obliged governments to intervene in the activities of the pharmaceutical sector by establishing medical products regulation;  In this context, medical products regulation is a public policy that restricts private sector activities in order to attain social goals set by the Government.

4 |4 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva n The overall objective of a National Regulatory Authorities (NRAs) for medical products is to ensure that all medical products (medicines, vaccines, blood products and other biologicals, traditional medicines and medical devices) that are used in a country are of assured quality, safety and efficacy and are accompanied by appropriate information to promote their rational use. n To fulfill this task NRAs need to be competent, capable, independent, with strong political back-up and to have clear authority to enforce established regulations. The role of National Regulatory Authorities

5 |5 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Where we are with national regulatory systems today (1)  ≈30% of NMRAs globally have limited capacity to perform all core regulatory functions  ≈90% of African NMRAs lack capacity to guarantee quality, safety, and efficacy  Manufacturers / applicants face a landscape of disparate regulations, frequent delays, and limited transparency As a result, needed medicines lack availability, affordability in low- and middle income countries  Fewer medicines are available in low-income countries than in the US, EU and other well-regulated markets.  Cost of inefficient regulatory systems drives up medicines prices.

6 |6 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Some summary observations:  Guidelines and assessment procedures are not up to international standards and are often of an administrative rather than technical nature;  Wide-ranging exemption clauses exist which are not justified by a risk assessment, for example for public sector imports or donations;  Inadequate resources severely limit technical assessment of dossiers;  In spite of resource constraints only few countries rely/refer on decisions made by other regulators (such as stringent NMRAs or by the WHO Prequalification Programme), or by other competent authorities. Where we are with national regulatory systems today (2) 26 country study in Africa

7 |7 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva What WHO is doing to support regulators (1) 1.Developing evidence, maintaining knowledge and understanding of situation and needs of regulatory systems worldwide. This is done by: – proactively seeking information on national level, including assessing national regulatory systems upon request from Member States – Internationally, by participation and contribution in regional and sub-regional regulatory networks: International Conference on Harmonization (ICH); Asia-Pacific Economic Cooperation Regulatory Harmonization Steering Committee (APEC RHSC); Organization of Islamic Cooperation; African Medicines Regulatory Harmonization Initiative (AMRH).

8 |8 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva What WHO is doing to support regulators (2) 2.Based on assessed needs, providing direct country support through technical advice, trainings, seminars, and other specific capacity-building activities – in accordance with the Institutional Development Plans (IDPs). 3.Developing and continuously improving tools to assist regulatory work (e.g. standards, guidelines, manuals, databases and other information materials, as well as tools for exchange of regulatory information): – Implementation of WHO Certification scheme on the quality of pharmaceutical products moving in international commerce - update and expansion to include starting materials

9 |9 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva What WHO is doing to support regulators (3) 4.Providing direct support to regional/sub-regional networks through technical advice, training, seminars, and other specific capacity-building activities including establishing subregional/regional centres of excellence and training networks (e.g. through Technical Working Group on Regulatory Capacity Development in Africa). 5.Organizing representation in regional and global regulatory initiatives and facilitating dissemination of information through different relevant platforms. 6.Promoting WHO’s regulatory strengthening work and its output to ensure visibility and accessibility to interested regulatory counterparts:

10 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Map of training activities by area of work and type of training

11 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva  Developing evidence: —Assessments of national regulatory systems conducted in Democratic Republic of Congo (DRC), Kenya and Zambia in 2014;  Providing direct technical support to Regional Economic Communities (REC): —Training provided in March 2014 to UEMOA countries on Common Technical Documentation (CTD) and on technical, scientific and administrative guidelines for registration of generic products;  ACP – African, Caribbean and Pacific. WHO/RSS activities in supporting ACP  regulators (1)

12 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva  Providing direct technical support Countries: —Training provided in July 2014 on Good Manufacturing Practices (GMP): Field work through on-site visit of local manufacturer in DRC; —Technical advice provided to countries on ad-hoc basis on the broad spectrum of pharmaceutical regulation  Promoting WHO Norms and standards: —Development of the revised version of the WHO/RSS Regulatory Technical Package containing relevant guidance for regulators. WHO/RSS activities in supporting ACP regulators (2)

13 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Regulatory Capacity Building for Influenza Vaccines in Global Action Plan (GAP) Countries Regulatory Function Activity Participants Marketing Authorization Training on quality assessment of influenza vaccines, 2013, USA6 countries Lot release & lab access QC training, , NIBSC, UK QC training and manufacturing, , NVI, Netherlands Participation in international proficiency study, , GAP countries 30 regulators 10 regulators 22 NRAs and manufacturers Regulatory Inspections GMP inspection training, 2011, Rep. S. Korea Fundamentals of GMP Influenza Vaccine Manufacturing, 2013, USA Regulatory Inspection Risk Approach, 2013, Brazil 36 regulators Clinical trials Clinical trial design for combination & influenza vaccines workshop, 2008, Switzerland GCP inspection training, 2011, S. Africa Regulatory requirements for the preclinical/non-clinical and clinical evaluation of influenza vaccines workshop, 2014, Thailand 40+ regulators and manufacturers

14 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva International Conference of Drug Regulatory Authorities (ICDRA)  The ICDRA conferences have been held biannually since 1980 with the aim of promoting exchange of regulatory information on medical products and collaborative approaches to issues of common concern;  ICDRA is a platform established to develop international consensus on regulatory matters;  After 30 years of existence ICDRA continues to be an important tool for WHO and medicines regulatory authorities in their efforts to harmonize regulation and improve the safety, efficacy and quality of medicines.

15 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Over the past thirty years, the main objectives of the ICDRAs have remained almost unaltered:  to promote collaboration between national medicines regulatory authorities.  to reach a consensus on the matters of common interest.  to facilitate timely and adequate exchange of information.  to discuss issues of international relevance. 1 st 1980 Annapolis (USA) 2 nd 1982 Rome (Italy) 3 rd 1984 Saltsjobaden (Sweden) 4 th 1986 Tokyo (Japan) 5 th 1989 Paris (France) 6 th 1991 Ottawa (Canada) 7 th 1994 Nordwijkerhout (Netherlands) 8 th 1996 Manama (Bahrain) 9 th 1999 Berlin (Germany) 10 th 2002 Hong Kong (S.A.R. China) 11 th 2004 Madrid (Spain) 12 th 2006 Seoul (Republic of Korea) 13 th 2008 Bern (Switzerland) 14 th 2010 Singapore 15 th 2012 Tallinn (Estonia) 16 th 2014 Rio de Janeiro (Brazil)

16 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva ICDRA is the regulators' "voice" In collaboration with the host country WHO is contributing in organization of ICDRA conferences:  Planning;  Development of the conference programme;  Liaison with the host country's NMRA;  Validation and approval of registrations;  Supporting participation of developing countries' regulators;  Organization of side meetings/events;  Technical and logistic support during the event;  Collation and preparation of the recommendations.

17 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva

18 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva

19 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva

20 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva What is regulatory harmonization? In a broad sense harmonization means harmonization of technical requirements for medicines regulation, i.e., legislations, guidelines, procedures, etc. Different types of the guidelines and other normative documents are available for regulators:  National (Individual counties);  Regional (e.g., EU, ASEAN, PANDRH, EAC, SADC, UEMOA, WAHO, etc.);  International (WHO, ICH, PIC/s). WHO guidelines (international) are available on most of the technical requirements for generic medicines

21 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Why regulatory requirements need to be harmonized? Current (not harmonized) environment Harmonized environment  Individual National Medicines Regulatory Authorities (NMRAs) governing medical products registration  Paperwork, technical requirements, and other registration steps differ across NMRAs  Manufacturers must invest significant time and effort in each registration, so a limited set of countries are targeted  No clear timelines for a drug to clear registration and be ready for the market  Little transparency before or during the process  Regional economic communities (RECs) and other country groupings covering the entire world  Common documentation, procedure, and decision-making framework across all RECs  Low cost to register in each additional country, so coverage is more broad and equitable  Streamlined process that is faster and easier  Clear understanding of the process by all parties involved

22 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Identification of technical documents for harmonization No need to invent a bicycle..  When appropriate guidelines exist elsewhere it is not necessary to develop new documents from scratch;  The simplest and most cost-effective way is to adopt the content and format of already existing guidelines, with, if necessary, modifications to accommodate the local situation.  True harmonization is not just development of common documentation - MOST EFFORTS SHOULD GO FOR THE IMPLEMENTATION! PIC(s)

23 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva African Medicines Registration Harmonization Initiative (AMRH) – Consortium of partners The overall objective of this initiative is to achieve a harmonized medicines registration process in countries belonging to the Regional Economic Communities (RECs), based on common documents, processes and shared information systems at the level of RECs. WHO's main role in this initiative is:  To provide technical assistance in development and implementation of harmonized approaches for registration of medicines; Support Technical Working Groups in 4 areas: Medicines Evaluation and Registration, Good Manufacturing Practices (GMP), Information management systems (IMS) and Quality Management Systems (QMS);  Support regulatory capacity building, training and joint activities. Chairing the Technical Working Group on Regulatory Capacity Development in Africa.

24 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva  Main objective – To facilitate harmonization, sharing of expertise and trust building.  EAC MRH specific objectives - establishment of a framework for: – Joint reviews and inspections of manufacturing sites; – Marketing authorization by EAC NMRAs.  1 st joint assessment series: 2010 – 2011 – Two products – Abacavir Sulphate tablets 60mg and Amikacin injection; – Outcome - Jointly accepted in January, 2011; – Countries’ approval took place after 3 – 7 months from the date of joint acceptance by EAC/WHO. Joint WHO/EAC assessment sessions (1)

25 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva  2 nd joint assessment series (TFDA data) – 4 sessions from July 2013 to April NoReference numberProduct nameCommon name and strength Date received by WHO Date received by TFDA Date of joint acceptance by WHO/EAC Date of registration by TFDA 1TFDA13/HM/0261 (WHO PQP No. RH039) Misoprost 200Misoprostol 200μg26/3/201326/6/20138th April th May TFDA13/HM/0262 (WHO PQP No. RH040) Pill 72Levonorgestrel 0.75mg 1/5/201326/6/20138th April th May TFDA13/HM/0290 WHO PQP No. MAL101 Falcimon 25/67.5 Artesunate 25mg + Amodiaquine 67.5mg 27/3/201316/7/20138th April th May TFDA13/HM/0291 (WHO PQP No. MAL102) Falcimon 100/270 Artesunate 100mg + Amodiaquine 270mg 27/3/201316/7/20138th April th May TFDA13/HM/0292 (WHO PQP No. MAL103) Falcimon 50/135 Artesunate 50mg + Amodiaquine 135mg 27/3/201316/7/20138th April th May 2014 Joint WHO/EAC assessment sessions (2)

26 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Lessons learnt from joint activities  Capacity (knowledge and skills) built for EAC Partner States NMRAs experts;  Quicker access of prequalified and jointly accepted medicines - Reduced timelines for registration ;  NMRAs scarce resources saved – No duplication of work;  Used as a platform for trust building among EAC regulatory experts;  Lays foundation for better cooperation among EAC NMRAs – potential for future mutual recognition of regulatory decisions among EAC Partner States NMRAs.

27 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Conclusions  Medical products regulation is not anymore a "single- player" activity;  Harmonization of regulatory requirements, 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.

28 | WHO Technical Briefing Seminar on Essential Medicines and Health Products, 3-7 November 2014, WHO Headquarters, Geneva Thank you! Graphic: