Capacity building and technical assistance to regulators; Regulatory cooperation and harmonization initiatives 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 E-mail: azatyans@who.int 1 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Why medicines need to be regulated? 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 often have difficulties to take informed decisions about all aspects of medicines, unless they are specially trained; To address these challenges governments have to intervene in the activities of the pharmaceutical sector by establishing medical products regulation. 2 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
The role of National Regulatory Authorities 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. 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. Resolution WHA67.20 of May 2014 - Regulatory system strengthening for medical products highest mandate. 3 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Where we are with national regulatory systems today (1) 30% of NMRAs globally have limited capacity to perform core regulatory functions; Manufacturers / applicants face a landscape of disparate regulations, frequent delays, and limited transparency. 194 WHO Member States: 20% 50% 30% Developed Variable Limited What is the result?.. Fewer medicines are available in low-income countries than in the countries with well-regulated markets. Cost of inefficient regulatory systems drives up medicines prices. 4 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
What WHO is doing to support regulators worldwide (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 subregional regulatory networks and initiatives: ICH; IPRF; APEC RHSC; AVAREF; DCVRN; African Medicines Regulatory Harmonization Initiative (AMRH). 5 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
What WHO is doing to support regulators worldwide (2) 2. Based on identified needs, providing direct country support through technical advice, trainings, seminars, and other specific capacitybuilding 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). 4. Providing technical 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. 5. Promoting WHO s regulatory strengthening work and its output to ensure visibility and accessibility to interested regulatory counterparts EMP Training Database: http://apps.who.int/prequal/ 6 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
7 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies Map of training activities by area of work and type of training
Supporting regulatory workforce development (1) A multi-stakeholder working group (US FDA, WHO, PAHO, RAPS, IFPTI and others) met to discuss a 2012 report by the Institute of Medicine of National Academies (US) that called for standards for the food and medical product regulatory workforce in low- to middle-income countries (LMICs). The working group identified a project to define minimal core competencies for Basic Level food and medical product regulatory professionals in LMICs i.e., the knowledge, skills, and abilities necessary for successful job performance, and to develop a curriculum framework to educate/train the regulatory workforce to the competencies. 8 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Supporting regulatory workforce development (2) The competency framework for Basic Level regulators was finalized. The competencies are classified accordingly: General: knowledge, skills, and abilities required by the entire food and medical product regulatory workforce in LMICs Technical: knowledge, skills, and abilities specific to both the food and medical product regulation Food: knowledge, skills, and abilities specific to the food regulatory workforce Medical Product: knowledge, skills, and abilities specific to the medical product regulatory workforce. Medical Product competencies were further classified into three categories: Regulatory Information and Strategy, Pre-approval/Approval, and Post-approval. 9 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Supporting regulatory workforce development (3) Curriculum framework for the Basic Level regulatory workforce was developed based on the competency framework: the framework represents the training content areas for Basic Level regulatory workforce; the curriculum framework content areas are categorized as Core (applying to both the food and medical product sectors), Food-Specific, and Medical Product-Specific. A gap assessment tool was developed to accompany the curriculum and competency frameworks, and to allow food and medical product regulatory agencies identify gaps in employee training/knowledge and develop a professional improvement plan. 10 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Supporting regulatory workforce development (4) Phase II Project is currently underway to: Implement and evaluate pilot programs with partner organizations and with LMIC regulators to implement training based on the assessments; Recommend strategies for expanding and sustaining training for regulatory professionals in low- and middle-income countries; WHO to host the final product once finalized and to facilitate rolling out in the Member States. 11 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Current challenges in low- and middle-income countries focus on Africa In many African countries most essential medicines are not readily available and accessible due to insufficient regulatory capacity and lack of harmonized technical requirements for medicines regulation; Poor uptake of new and existing health solutions costs millions of lives across low-income countries; Lack of essential medicines contributes to disparities in health and life-expectancy between low-income African countries and high-income countries outside the continent. 12 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Can harmonization help? 13 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
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 14 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Potential benefits of harmonization Potential for savings/greater reach via generic equivalents and increased competition Enhanced ability to implement pooled procurement models National Governments Manufacturers (Local and International) NMRAs Greater process transparency Shorter time to approval Greater incentives to prioritize dossier submissions Improved access to regional markets Patients / consumers Increased capacity More timely & cost effective authorization processes Enhanced quality of the MA decision More effective medicines control Donor Community Quicker access to priority essential medicines of assured quality at more affordable prices Higher patient reach for a given level of support 15 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
African Medicines Registration Harmonization Initiative (AMRH) a Consortium of partners Consortium Partners Other Stakeholders COHRED Consortium and major stakeholders convened in February and November 2009 NMRA Representatives Regional Economic Communities and Organizations (RECs) 16 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies 16
WHO support for medicines regulatory harmonization in Africa: example of East African Community (1) Promoted harmonization in EAC region through its capacity building component. Regional training on Common Technical Documents (CTD) format and GMP inspections; EAC experts' participation in the WHO Prequalification of Medicines Programme since 2003 Assessment of dossiers submitted to WHO PQ; GMP inspections as observers; Three months rotational post at WHO HQ. Normative work - Developed and approved technical guidelines in the 4 areas: Medicines Evaluation and Registration, Good Manufacturing Practices, Information management and Quality Management. 17 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
WHO support for medicines regulatory harmonization in Africa: example of East African Community (2) Three successful WHO- EAC joint assessments have been concluded; First pilot in 2010-2011: 2 products PQ by WHO, MA by Uganda, Tanzania, Kenya; Second joint assessment in 2013-2014: 5 products PQ by WHO, MA by Uganda, Tanzania (including Zanzibar), Kenya, Rwanda and Burundi; Joint EAC-MRH / Swissmedic / WHO Clinical Review of two biotherapeutic products (Avastin 100mg and 400mg and Herceptin 150mg and 440mg), Entebbe, Uganda, 19 23 October 2015 resulted in the recommendation of 2 products for licensing in the EAC. 18 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Lessons learnt from joint activities in EAC 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. 19 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Almost 85% of Sub-Saharan Africa covered by Summary Project Proposals already completed or in the process REC progress Completed or in-process RECs Countries covered Total members* % pop covered EAC & OCEAC EAC, OCEAC, ECOWAS EAC, OCEAC, ECOWAS, SADC 12 (20%) 26 (46%) 41 (74%) 11 26 41 17% 45% 72% EAC *Tanzania in both EAC and SADC (but will go with EAC); UEMOA/ECOWAS are working out overlap OCEAC WHO, NEPAD and World Bank: supporting East African Community which has already received funding and is implementing the project; continuing to work with other RECs to finalize their proposals. SADC Source: BCG analysis 20 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies 20 20
Why Regional Economic Communities (RECs) based approach? RECs have a strong mandate to promote common trade, economic and market opportunities to those countries that constitute their member states. In addition to economic development, many RECs work to promote social development and are increasingly active in the healthcare field. Several RECs have already supported harmonization of medicines registration by developing common pharmaceutical policies and operational plans. 21 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Why Regional Economic Communities (RECs) based approach? But.. a number of overlaps and politically complicated environment substantially affect the situation 22 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
True harmonization is NOT just development of common documentation what else is needed? Appropriate legislative and regulatory requirements: Legal framework to define the basis and conditions for collaboration and work sharing/acceptance of information and decisions; Regulatory framework defining the practical arrangements; Technical framework: applicable guidelines Application of these provisions: Operational procedures for implementation; Appropriate interpretation of the requirements: Competence of the personnel; Capacity development, training, etc. 23 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Success factors for harmonization initiatives (1) Well elaborated and clearly understood vision, mission, roles and responsibilities; Political will and continuous support; Effective management and administration through the secretariat and/or steering committee; Active participation of all potential stakeholders (NMRAs, industry, development partners); Ownership by the NMRAs; 24 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Success factors for harmonization initiatives (2) To be based on the modern science and reaching the consensus; Engagement by all parties to implement the documents developed and to follow them; Well defined decision trees and procedures; Adequate human and financial resources; Transparency, effective communication and RESPONSIBILITY. 25 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
RHT/RSS activities in supporting the local manufacturing of medicines The aim is: To develop a strategy for selection of products on the Essential Medicines List that could be considered for local manufacturing in LMICs with no or little development and manufacturing experience (start-up situations). 26 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
WHO/RHT activities: Assessment of the WHO EML 1. Framework for the identification of the spectrum of risks associated with the manufacture, including packaging and testing; 2. It presents the rationales for risk designation specifically in the context of start-up of manufacturing in LMICs; 3. The identified risks may then be considered in total to inform recommendations to move forward with subsequent stages of project development. 27 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Risk Ranking of Product Categories by Potential Loss of Control and Contamination Risk 28 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
International Conference of Drug Regulatory Authorities (ICDRA) WHO role 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. 29 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Next 17 th ICDRA Cape Town,South Africa, 2016 30 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Conclusions Medical products regulation is not anymore a "singleplayer" 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. 31 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies
Graphic: www.eauc.org Thank you! www.who.int/medicines 32 WHO Technical Briefing Seminar: Essential Medicines and Health Technologies