1. Regulation of medicines and other health technologies. The future of regulation, where are we going? EMP TBS November 2014, Geneva Dr Lembit Rägo Head, Regulation of Medicines and other Health Technologies, Essential Medicines and Health Products World Health Organization E-mail: ragol@who.int

2. 2 |2 | Content What type of health products and what type of regulation? Where are we now? Regulatory convergence, harmonization and collaboration Key elements for success Concluding remarks

3. 3 |3 | Where are we now? Majority of WHO Member States either medium, small or very small countries Most regulators do not have the resources – both human and financial - to manage existing, or rather ever increasing obligations and expectations No one "ball game" for "big fish" and "small fish" – in fact, it seems the capacity gap between "big fish" and "small fish" is increasing Big one can take care of themselves, but how to get the rest moving in order to save lives? How with existing/anticipated resources secure patients in increasingly complex world?

4. 4 |4 | Who sets the standards? Are standards harmonized? New innovative medicines –International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Multisource (generic) medicines –WHO has complete set of regulatory guidance starting from GMP and ending with bioequivalence/biowaiver guidance Other types of medicines –Vaccines, blood products, cell therapies, "biosimilars" - biologicals –Traditional and complimentary medicines … Medical devices including in vitro diagnostics (IVDs) Combination products – device plus medicine etc. For many product types and issues, no one single set of standards – regulatory convergence and harmonization

5. 5 |5 | International Conferences of Drug Regulatory Authorities (ICDRA) Biennial Global meetings bringing together regulators from around 100 nations Promoting information and best practices exchange, cooperation, harmonization and convergence Several initiatives started in ICDRA environment –ICH initial discussions –AMRH initiative initial discussions –Reports from various convergence and harmonization initiatives

6. 6 |6 | New: Harmonization of pharmacopoeias Pharmacopoeias – need for more change … Pharmacopoeial Discussion Group (PDG) –ICH parties - US, Japanese and European Pharmacopoeia –WHO observer Harmonization beyond PDG – WHO took initiative convening all functioning pharmacopoeias for further convergence and harmonization: The 1 st International Meeting of World Pharmacopoeias, 29 February – 2 March, 2012, Geneva; Switzerland The 2nd International Meeting of World Pharmacopoeias, 18-19 April 2013, New Delhi, India … 2014 meetings

7. 7 |7 | Harmonization of regulatory requirements is important Objective of drug regulation: TO IMPROVE AND PROMOTE PUBLIC HEALTH Harmonization aimed to diminish duplicative efforts, creates "common language", can facilitate cooperation and access to medicines In case of harmonization of regulations the main objective should be: –MEASURABLE PUBLIC HEALTH GAINS There may be other gains, but these should be in the centre

8. 8 |8 | How to achieve harmonization? What are the “lessons learned” from examples of well-harmonized regulation? What are the key elements of success? How can these lessons be applied to biomedical research and medical product development?

9. 9 |9 | Harmonization initiatives Inter-regional, regional and sub-regional – ICH, APEC, Pan American Network for Drug Regulatory Harmonization (PANDRH), ASEAN, SADC, EAC (part of AMRHI), Gulf Cooperation Council etc. Not harmonized! – Good Harmonization Practice (GHP) needed? –Different organization – with or without strong secretariat –Different involvement of industries and other parties –Different in terms of implementation – some focused on implementation, others rather focused on convergence of regulatory thinking –Different focus technical areas/products –…

10. 10 | Key elements of success for regulation (1) Enabling environment and foundation –Good Governance principles implemented –Modern legal systems allowing certain flexibilities Political will and shared common vision Similar socioeconomic development of participating countries Participants functional regulatory authorities with necessary capacity and resources available

11. 11 | Key elements of success (2) Willingness to invest into harmonization Effective governance and secretariat Willingness to cooperate and compromise Commitment for implementation and updating/revision Commitment for applying Good Regulatory Practice principles when implementing …

12. 12 | Timely access to better (hopefully) medicines ladder Good Decision Making Practices Good Regulatory Practices based on CTD, alignment and effective cooperation and worksharing Harmonization and convergence of technical requirements in conjunction with harmonized training principles and model core curricula for regulators Applicable modern laws and enabling legal system General Good Governance in Public Sector, including transparency and accountability

13. 13 | Other experiences of success EU experiences – few regulators from 28 MS take the active lead but all benefit (harmonization major enabling factor) Joint reviews of clinical trial applications/products across borders –AVAREF –Medicines Prequalification Programme jointly with EAC regulators –IGDRP – plans joint reviews as well Promoting international convergence, harmonized standards and good review practices by staff exchange –Medicines prequalification has a 3 months rotational fellow position for quality assessors

14. 14 | Concluding remarks (1) WHO has promoted regulatory collaboration, convergence and harmonization long time and will continue to do so being open to new ideas Making medicines is not any more a "local" business and the era of only locally operating regulators starts to end The future of medicines regulation is more in collaboration and networking; regulators starting to function more as a functional network rather than individual players, and individual players focusing on what they can give the best added value

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16. 16 | 16 th ICDRA in 2014

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18. 18 | Concluding remarks (2) 14 th ICDRA recommendations in 2010 for Medicines Regulatory Authorities:  Take account of one another’s work with a view to improving the efficiency of the global regulatory system.  Commit resources to form cooperative networks based on uniformity of standards and inspection systems.  Engage with regional and international initiatives promoting harmonization, information sharing and use of data generated by other regulators as a tool for improving timely access to medicines and medical products.

19. 19 | Concluding remarks (3)  It is clear that NOT ALL national regulators can fulfill themselves ALL the functions and decisions have to be made nationally on which areas to focus and build capacity, and in which areas rely on other regulators work  Harmonization alone cannot help, but can form a solid basis for the new regulatory paradigm to evolve in the future –  Doing locally what nobody is doing/can do for you, (added value) and decide in which area you invest to specialize to be a "world class player" in the Regional/Global Network