1. OVERVIEW OF MEDICINES REGULATORY HARMONIZATION BENJAMIN K BOTWE MSc., MPA, FGCP, FPCPharm. CONSULTANT

2. OUTLINE Harmonization Initiatives Background to African Medicines Regulatory Harmonization (AMRH) Pharmaceutical Manufacturing Plan for Africa (PMPA) African Medicines Agency (AMA) African Medicines Registration Harmonization (AMRH) Implementation East African Community (EAC) Communite Economique et Monitaire du L’Afique Centrale (CEMAC) Southern Africa Development Cooperation (SADC) Economic Community of West African States (ECOWAS) Benefits

3. HARMONIZATION INITIATIVES International Conference on harmonization of Technical Requirements for the Registration of Medicines for Human Use (ICH) Pan American Health Organization (PAHO) PANDRH Association of South East Asian Countries (ASEAN) European Medicines Agency (EMA) African Medicines Registration Harmonization Project (AMRH)

4. BACKGOUND Rationale for Harmonization Limited Progress due to insufficient resources for implementation and coordination Preventing duplication of efforts by member states Improve the accessibility and availability of essential medicines Improve on the quality assurance of medicines Effective use of limited human and financial resources Improved sharing of scientific knowledge and expertise between regulators and industry practitioners Easier to mobilize and donor community support structure

5. BACKGROUND As Africa embarks on the trajectory of economic transformation, the pharmaceutical manufacturing industry is promising creation of jobs, economic benefits, improved social and human outcomes as well as stimulating other economic activities across its complex value chain. A vibrant pharmaceutical manufacturing sector in Africa has the potential to contribute to improved access to medicines, better public health outcomes and economic growth.

6. BACKGROUND The 55th Decision of the AU {Assembly / AU/Dec.55(IV)} taken during the Abuja Summit in January 2005 requested the AU Commission to develop a Pharmaceutical Manufacturing Plan for Africa (PMPA) within the framework of the New Partnership for Africa’s Development NEPAD.

7. BACKGROUND Subsequently; the African Union Ministers of Health made a decision in 2007 to develop a PMPA business Plan which was later endorsed by the 19th AU Assembly complemented by AU Roadmap on Shared Responsibility and Global solidarity for the AIDS, TB and Malaria response in Africa {Assembly AU/Dec.442 (XIX)} which among others, emphasizes the need to accelerate and strengthen regional medicines regulatory harmonization initiatives and lay foundations for a single African regulatory agency.

8. BACKGROUND In recognition of the need for a conducive regulatory environment for local production and trade in pharmaceuticals on the continent, the African Medicines Regulatory Harmonization (AMRH) Initiative was established in 2009, under the coordination and leadership of the NEPAD Agency. All these efforts provide a foundation for establishment of the regional and continental medicines regulatory agencies.

9. BACKGROUND While the East African Community has embarked on the process of drafting a bill for establishment of the East Africa Community Medicines and Food Safety Commission (EACMFSC), the West African region is next on the line. Furthermore, at the First African Ministers of Health meeting jointly convened by the African Union and World Health Organization (WHO) held in Luanda, Angola, in April 2014; the milestones towards the establishment of the African Medicines Agency (AMA) were endorsed.

10. PMPA The overall aim of PMPA is to provide a mechanism for improving health outcomes through access to medical products and technologies to the African population strengthening regulatory systems; boosting research and development; promoting intra-African trade and supporting the local pharmaceutical industry.

11. AMA The Council of Ministers requested the African Union Commission (AUC), the NEPAD Agency and the World Health Organization (WHO) in collaboration with other stakeholders to elaborate AMA’s legal and institutional framework including financial implications for its establishment.

12. AMA The Ministers committed themselves to Prioritizing investment for regulatory capacity development; pursue the efforts towards convergence and harmonization of medical products regulation in RECs allocate adequate resources for AMA. They further endorsed the establishment of the AMA Task Team to spearhead the process.

13. AMA More recently in January 2015, the AU Executive Council Decision, { EX.CL/Dec.857(XXVI))} endorsed the Milestones for the establishment of a single medicines regulatory agency in Africa within the context of the African Medicines Regulatory Harmonization Programme, which is part of the framework of the PMPA.

14. AMA The first AMA Task Team meeting held in Addis Ababa, Ethiopia on 25-26 November 2014 brought together more than 30 experts who reviewed among others; the regulatory pathway in the African context and harmonization approaches and the Luanda Decision on AMA. reviewed the key milestones towards AMA establishment, the Terms of Reference of the task team to facilitate the establishment of AMA and adopted a 4-year Plan of Action (2015-2018) for the task team to be supported by AUC, NEPAD Agency and WHO joint Secretariat. NEPAD Agency is supporting the development of the legal and institutional framework for AMA and is responsible for stakeholders’ consultation process as part of the 4 year plan agreed by the AMA Task Team.

15. 1 ST AMA TASK TEAM MEETING

16. AMRH IMPLEMENTATION AMRH Programme is being implemented as a continental initiative aimed at strengthening the continent’s regulatory capacity through medicines regulation harmonisation in the regional economic communities. So far roughly 85% of sub-Saharan Africa has been covered by MRH Proposal frameworks or implementation is in progress. In terms of the pharmaceutical sector development there is need for optimizing the African Market for new medical products and technologies. This will lead to increased access to medical products and technologies.

17. AMRH IMPLEMENTATION The AMRH Programme is focused on three key interventions areas namely: Policy and regulatory reforms; Regulatory Capacity Development and Knowledge Management. Through the AMRH platform, a draft Model Law on Medicines Regulation & Harmonization in Africa has been developed and endorsed by Pan African Parliament (PAP) Committee on Health, Labour & Social Affairs

18. AMRH IMPLEMENTATION Model law has been discussed in all the RECs Model law has so far been wholly adopted by some countries while others have used it to amend existing legislation Regional Centres of Regulatory Excellence (RCOREs) have been appointed across the continent African Pool of regulatory experts created All geared towards the development of a harmonised curricula and regulatory capacity development strategy for Africa.

19. AMRH IMPLEMENTATION Funds mobilization is on going to support MRH in RECs MRH proposals have been supported in EAC, ECOWAS and currently on going in CEMAC and SADC MRH launched in EAC and ECOWAS Pharmacovigilance framework for Africa developed with support from the WHO-CC in Ghana MRH taking lead role in search and trials for medicines for emerging diseases of public health concern (EBOLA etc.)

20. EAC Burundi, Rwanda, Kenya, Tanzania, Uganda and Zanzibar Chapter 21 (Article 118) of the EAC Treaty of 7th July 2000 provides the legal framework on EAC Regional Cooperation on Health. This Treaty provides for the harmonization of drug registration and regulation; harmonization of drug registration

21. EAC procedures; development of common drug policy, the establishment of quality control capacities, good procurement practices; national health policies and regulation to promote the exchange of information on health issues in order to achieve quality health within the EAC. EAC MRH project was launched in March 2012

22. EAC The EAC has developed and approved guidelines in medicines registration, GMP Inspection and Quality Management Systems (QMS). The region has also established a common Information Management Systems (IMS) for the participating NMRAs.

23. EAC EAC Member States have also embarked on exchange programmes with the view to foster peer learning and sharing of available human resources in the region. As a means of building capacity, the EAC MRH project with support from partners hosts training programmes for NMRA staff Undertaken joint dossier assessments and inspections with technical support from WHO

24. CEMAC/OCEAC Cameroon, Congo Brazaville, Gabon, Tchad, Central Africa Republic, Equitorial Guinea, South Sudan*** Progress has been made in the harmonization of Pharmaceutical policies in Economic and Monetary Community of Central Africa (CEMAC)/ Organization for the Coordination of Endemic Disease Control in Central Africa (OCEAC) Region. Capacity development programs are on going legal deficiencies in legislative and regulatory framework are being review using the AU Model law as a starting point.

25. CEMAC/OCEAC Harmonization efforts are being made in the areas of medicines registration, pharmaceutical inspection and pharmacovigilance systems strengthening QC laboratories are also being supported Consultations on the AU Model law has already taken place in the region Yet to launch the CEMAC/OCEAC Medicines harmonization project

26. SADC South Africa, Lesotho, Swaziland, Botswana, Zambia, Zimbabwe, DR Congo, Malawi, Namibia, Madagascar, Angola etc. Harmonization proposals developed and funding being sought for ZaZiBoNa Initiative on going – 8 joint dossier assessments held already Now opened to other members to join

27. ECOWAS Benin, Burkina Faso, Cape Verde, Cote D’Ivoire, Gambia, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone, Togo March 2011, WA-MRH project proposal was submitted to NEPAD for support August, 2012 NEPAD visit to WAHO Head quarter to strengthen collaboration between WAHO and UEMOA November, 2012 meeting in Pretoria to outline the MOU between WAHO and UEMOA, and implementing framework

28. ECOWAS In April, 2013, WAHO and UEMOA, reviewed and developed an Agreement alligned to the 2009 MOU Follow up meeting between DG of WAHO and UEMOA Commissionner and team to discuss an approach for an effective collaboration of the MRH project and other health issues From 17-18 April, 2014 WAHO/UEMOA met to discuss and sign the shared regional mechanism for MRH activities in West Africa- roadmap was developed

29. Efforts made so far Towards MRH in ECOWAS Project Proposal on Medicines Registration Harmonization (MRH) finalized and sent to NEPAD for support Common Technical Documents (CTDs) and training manual developed for the MRH implementation by member states Communication and meetings with NEPAD and 7 Member States initiate working together Training of Regulators on CTDs MRH Steering Committee, Technical Working Groups March 2011 2010-2011 2011-2012 Q2 2013 Q2 2013-2014 2008- 2009 PRSAO/ WAHO

30. ECOWAS Terms of Reference developed and adopted for the Steering Committee and the Technical Working Groups TWGs 1.Dossier Evaluation 2. Inspections 3. Quality Management System, 4. Quality Control 5. Medicines Safety 6. Information Management System, 7. Policy, Legal and Regulatory

31. Efforts done so far Towards MRH in ECOWAS (NMRAs) trained on Good Manufacturing Practices (GMP)- QMS, inspection processes and prequalification requirements. Besides the CTD document developed Training manuals on: – Submission of Dossiers for Application for Marketing Authorization – Format for Manufacturing Facility Inspection. – Common Technical Documents for the Registration of Medicines – Format for Quality Control Assessment. – Formats for Medicines Register – Formats for Presentation of Evaluation Reports. Political Endorsement by Assembly of Health Ministers, 4-5 th April, 2013, Cape Verde

32. WAHO Strategies to Accessing Quality Essential Medicines  Strengthening of the capacity of quality control laboratories  Strategies in the fight against counterfeit and illicit medicines market  Medicines and vaccines Safety, information services  Strengthening the accessibility of quality medicines through sound procurement systems  Harmonized TRIPs policy and guidelines for adoption by ECOWAS member states to employ WTO TRIPs flexibilities.  Strengthening of the capacity of local manufacturing companies

33. Strengthen the Capacity of National Medicines Regulatory Authorities GLP-Good Laboratory Practices BA/BE studies guidelines, WAHO Certification and prequalification Schemes (Ghana spear heading) Training of NMRAs and Manufacturers on the CTD/MRH 7 NMRAs become ISO Certified and other Accreditations Peer reviewing, mentoring towards harmonization 2013-2016 NMRAs collaborate effectively with themselves and Manufacturers 2013-2015 First meeting in Abuja, Sept 2012 (2010-2012) 2011- 2016 2011-2017 Q4 2013 2013- 2016 NMRAs Strengthened in Pharmacovigilance World Bank support funds for MRH activities (1 year) 2014-2015

34. Strengthening of the capacity of quality control laboratories Guidelines and training manuals developed for QC Laboratories Quality Control Managers Trained to apply the documents & SPACE Good Laboratory Practices- Acquisition of knowledge centered on Safety, Productivity, Accuracy, Credibility and Education QCL play key roles in ensuring availability of quality and safe medicines for public health intervention and the drive towards prequalification of local manufacturers which requires adequate laboratory support 1.Quality Control Laboratory Manual and Trainers Manual 2.Quality Control Safety Manual and Trainers and Trainees Manuals 3.Quality Control Records Manual and Trainers and Trainees Manuals 4.Quality Control SOPs Manuals and Trainers and Trainees Manuals 17 NQCL assessed and categorised into three groups Upgrade to Reference Quality Control Laboratories 2013-2018 Q2 2013 June 2012 Sept 2013 2010-2011 2010 WAHO Certification Scheme PSM, FPP developed and published WAHO Pre-qualification Scheme BA/BE guidelines Regional prequalified quality control reference laboratories 2014-2018. Equipment prevention and maintenance plan 2014-2018

35. Strategies in the fight against Counterfeit and illicit medicines market Regional Action Plan ECOWAS Medicines Anti-counterfeit Committee formed (EMACCOM) Regional legal and legislative framework Inauguration of the ECOWAS Medicines Anti-counterfeit Committee (EMACCOM) ECOWAS Parliamentarians, Trade Commission and other stakeholders have adopted the legal and legislative framework for implementation in 2013 National Medicines Anti- counterfeit committee Common assessment tools to collate comparable data on the counterfeit situation in the sub- region (2013-2016 ) Anti-counterfeit Technology for identifying counterfeit medicines Communication Strategies for stakeholders involvement and media Advocacy, Pharma Policy and Governance June 2010, Sept 2011, Sept 2012 June 2011 Jan 2012, April 2012 July 2012 April 2013 Q1 2014 Medicine alert systems Q3 2013 WHO/ NAFDAC Situational Analysis of the counterfeit and illicit trade in medicines

36. Safety Medicines and Vaccines, Information Services Situation Analysis, sensitization and capacity building workshop in Adverse Drug Reaction Supported six Member States with Laptops Linked to WHO Drug Information Centers in Sweden -Uppsala through Vigiflow Strengthen capacity in communication and crises management in PV Free movement of goods and people across the region established by the ECOWAS treaty. Cultural, economic and social inter-relationships in the sub-region, Essential that every nation has a pharmacovigilance system and that information from these systems are shared Experts were sent to monitor and provide hands on training where needed M&E, Drug Information Systems in the regional and District Hospitals May 2010 2011 Feb 2012 2014-2020

37. Regional TRIPs Flexibilities Policy /Legislation and Guidelines for the ECOWAS region Regional TRIPS policy/ legislation and guidelines developed Stakeholders meeting to validate and adopt the documents Advocate at AHM for adoption of the regional policy and guidelines of the Intellectual Property by Member States Incorporation and enactment of policy/legislation into member states national IP laws Implementati on of TRIPS flexibilities Member States Sensitization workshop to strengthen the capacity of Directors of the Ministries of Health, Trade and Justice to understand and apply the TRIPS flexibility and related waivers July 2013 Request to be sent to WTO TRIPs Council for extension of the Flexibilities on Pharmaceutical products for LDCs March, July 2012 Oct 2012 April 2013 2013- 2015 2014-2017 Consultant engaged for six months to support in the activities for the establishment of the Intellectual Property flexibilities in the ECOWAS (2013)

38. Strengthening of the Local Manufacturing Capacity Feasibility studies, Business plan and Drawing plans for plants 2009-2010 Good Manufacturing Practices (GMP) through training based on WHO modules 1,2,3 Facilitated Loan Support EBID banks Financially Supported Six Units towards WHO prequalification of products and facilities 265 Production Units in the region 10 would be WHO prequalified by 2017 Support with soft loans under the Public –Private Partnership Initiative Improve Stock Security of ARVs, TBs and Malaria Public Health Commodities Create a platform for Technological Transfer 2009- 2010 2010-2011 2011-2012 2011-2013 2013-2016 Tax exemption for API, equipment for locally produced medicines 10% on same products imported Endorsed by Health Ministers at AHM in Cape Verde 4-5 April 2013 Pharmaceutical Manufacturing Plan for West Africa (PMPWA) as part of ERPP Multi-sectorial meeting on Charter to discuss content and form a consortium for Implementation 29-31 Oct, 2013

39. Benefit of MRH to ECOWAS Will increase access to safe, quality, efficacious, affordable priority essential medicines by reducing the time it takes for beneficial therapies to reach patients in need. Governments will make substantial savings; enjoy additional economies of scale via pooled procurement Common documentation will enable and facilitate collaborative mechanisms at the regional-level, e.g. Information sharing and joint inspections/evaluations; translate into improved registration processes and operational efficiencies at the national level Local manufacturers will benefit from an expanded regional market as technical barriers to trade are reduced

40. BENEFITS TO ETHICAL MANUFACTURERS Joint Dossier Assessments lead to: Quicker market access to safe and effective new drugs Lower costs due to centralized registration Simplified submission of application due to compliance with a single Common Technical Documents across RECs rather than multiple country requirements Quickening of the registration time cycle Reduced cost and time due to single inspection by a regional joint inspection team rather than multiple inspections by individual country teams

41. Common submission and assessment of Clinical trial applications based on harmonized guidelines Coordinated clinical trial monitoring and reporting Ground work for multinational studies of ethical factors in drug development BENEFITS TO ETHICAL MANUFACTURERS

42. Effective exchange of information between industry and regulators Improved capacity building of regulatory staff Exchange technical expertise and knowledge sharing Availability of scientific and practical knowledge for updating technical guidelines BENEFITS TO ETHICAL MANUFACTURERS

43. THANK YOU FOR YOUR KIND ATTENTION