Medicines Regulation: Introduction

1. Medicines Regulation: Introduction EMP Technical Briefing Seminar, November 2011 Dr Lembit Rägo Coordinator Quality Assurance and Safety: Medicines Essential Medicines and Pharmacutical Policies World Health Organization Geneva, Switzerland E-mail: ragol@who.int

2. Medicines work in WHO HQ – in Health Systems and Services Cluster (HSS), ADG Dr Carissa Etienne • Department of Essential Medicines and Pharmaceutical Polices (EMP) • Two teams • Medicines Access and Rational Use (MAR) • Quality Assurance and Safety: Medicines (QSM) • Two units (teams) attached to Director's office • Medicines Information and Evidence for Policy (MIE) • Medicine Programme Coordination (MPC) • Collaboration with other clusters/departments/units • Vaccines and biologicals (IVB/QSS) – vaccines prequalification • Essential Health Technology (EHT) - diagnostics prequalification • Disease oriented programs • Other programs …

3. Active collaboration with other international, regional and national organizations • UN family & international organizations: • UNICEF, UNFPA, UNIDO etc. • MSF • Regional • Council of Europe/EDQM • EMA/EU • NEPAD • Professional and scientific • FIP, IUPHAR, ISPE • National • NMRAs

4. QSM Technical Programmes • Regulatory Support • International Nonproprietary Names (INNs) • Quality Assurance • Anticounterfeiting • Safety (Pharmacovigilance) • Prequalification of Medicines • Quality Assurance and Safety of Blood Products and Related Biologicals

5. Why medicines are special category of products? • Consumers, patients and health care workers have limited capacity to judge there • SAFETY • QUALITY • EFFICACY

6. Usual perceptions may not help in Making judgements about medicines … Taste Appearance Smell

7. Are all medicines safe, effective and meet quality criteria? • No, they are not • Some are safe, but not effective or necessarily meet the quality criteria • Some may be effective, meet quality criteria but are not safe • Some meet quality criteria but are not necessarily safe or have any efficacy

8. Quality - Safety • Some safety parameters are determined by quality • Some safety parameters are determined by the intrinsic properties of active pharmaceutical ingredient(s)

9. What type of medicines we have? • Originator products • Multisource (generic) products • KEY – INTERCHANGEABILITY, more important THERAPEUTIC INTERCHNGEABILITY • ALL LITERATURE IS BASED ON ORGINATORS • No interchangeability – NEED FOR NEW SAFETY and EFFICACY DATA, NEW BOOKS HAVE TO BE WRITTEN • Other type of products • Biological products including vaccines and blood products • "Biosimilars" • Radiopharmaceuticals • Traditional medicines

10. What type of regulations exist and how they differ? • For innovator products proof of QUALITY, SAFETY and EFFICACY is needed • For multisource products QUALITY, safety and efficacy data is referred to the originator providing only evidence about interchangeability (bioequivalence, clinical testing, in limited cases dissolution data)

11. Regulations: Global vs National • National regulations still differ a lot • What is ICH and what it is not? • Regional harmonization initiatives • Do global norms exist for generics?

12. In book: Drug Benefits and Risks, Chapter 6, 2008

13. Main regulatory functions • Table 1. Principal medicines regulatory functions • Licensing of the manufacture, import, export, distribution, promotion and advertising of medicines • Assessing the safety, efficacy and quality of medicines, and issuing marketing authorization for individual products • Inspecting and surveillance of manufacturers, importers, wholesalers and dispensers of medicines • Controlling and monitoring the quality of medicines on the market • Controlling promotion and advertising of medicines • Monitoring safety of marketed medicines including collecting and analysing adverse reaction reports • Providing independent information on medicines to professionals and the public • Source: WHO Policy Perspectives on Medicines no 7, 2003.

14. Is quality of medicines a problem? • Yes, a HUGE problem • If we would have the same compliance with norms and quality in aircraft industry Globally • approximately 25% planes would not take off the grounds • 10% would crash and kill the people (treatment failure = killing in some cases; toxicity etc. )

15. Quality can not be assessed, tested or inspected into the product, BUT It has to be built into it!!

16. Shifting the regulatory paradigm during the history (1) • From elementary quality requirements to safety and efficacy • From quality control of finished product to control of quality of manufacturing (inspection) • From quality control of finished product and inspection of manufacturing sites in general to more understanding the processes and product specific processes involved • From rigid limits to agreed upon beforehand set of limits which can be used by manufacturers in a more flexible manner (ICH QbD) • …..

17. Shifting the regulatory paradigm during the history (2) • Increased role of science – new molecules, new advanced therapies and combination therapies (device + medicine, etc) • From national to international – not a single regulator today can work meaningfully in isolation and not using other regulators experience/knowledge/information • Increasing need to decide what regulatory functions to fulfil nationally and what expertise/capacities to build nationally • Increasing need for harmonization, collaboration and cooperation • The future in medicines regulation is in effective collaboration and cooperation

18. Science and medicines regulation (example): European Medicines Agency (EMA) - First Scientific Workshop On Nanomedicines, 2-3 September 2010, London • Emerging therapies such as nonomedicines give rise to questions on the appropriateness of current regulatory frameworks, the relevance and adequacy of existing requirements and guidelines, and on the availability of adequate expertise to regulators. • Scientific challenges arise from the limitations of current testing methods and the reliability of novel ones, because of the 'nanosize' and the unique behaviour of such nano-systems in biological structures. • Examples of approved nonomedicines: • the anti-neoplastic agent Caelyx includes stealth liposomes of doxorubicinehydrochloride; • the antineoplastic agent Mepact contains mifamurtide in multilamellar liposomes; • the antineoplastic agent Abraxane contains paclitaxel nanoparticles bound to human serum albumin; • the immunosuppressant Rapamune contains sirolimus particles in nanocrystal colloidal dispersion.