Anthony Serracino Inglott Chairman of the Malta Medicines Authority

1. Medicines Authority 203,Level 3, Rue D’Argens, Gzira,GZR 1368 Tel: (+356) 2343 9000 Fax: (+356) 2343 9161 Email: anthony.serracino-inglott@gov.mt Medicines Authority Harmonisation of Medicines Regulatory Affairs Anthony Serracino Inglott Chairman of the Malta Medicines Authority

2. Regulatory Harmonisation • Achieving a common public health goal • Technical guidelines • Uniformity • Participation of all stakeholders • Convergence-based approach • Similar • Aligned • Standard and scientific principles • Similar practices and procedures • Technical guidance documents

3. Regulatory Harmonisation • International recognised standards • Quality • Safety • Efficacy • Global approach to the treatment of medicines with dignity as distinct from ordinary items of commerce. • World heritage of mankind. • Increase access to internationally certified medicines. • Tool towards a declaration by the United Nations that access to medicines certified to international standards is a human right.

4. Regulatory Harmonisation • Harmonisation goes further than development of common documentation • Building competence and trust • Communication and collaboration • Collaborative approaches to drug registration

5. Regulatory Harmonisation What can we do to increase access to new medicines whilst ensuring consistent standards for Quality, Safety and Efficacy?

6. Regulatory Harmonisation Access Duplication Sharing resources Collaboration Regulatory sciences expenses

7. Regulatory Harmonisation • Benefits of Regulatory Harmonisation • Standardisation of documentation • Format • Content • Improve the capacity of regulators. • Bring new therapies to patients faster and at lower cost.

8. Why regulating drugs? • 1930s United States: a tragic mistake in the formulation of sulfanilamide elixir • 1960s Europe: thalidomide tragedy

9. Pharmacopeias • The quality of medicines was established through the development of the Pharmacopeias which lead to: • Harmonised specifications for substances of different origins • Transparent monographs • Specifications and valid analytical working methods • Common Reference Substances

10. Pharmacopeias 1820: United States Pharmacopoeia Latest edition USP 39-NF 34 (November 2015) 1864: British Pharmacopoeia Latest edition BP 2016 (August 2015) 1886: Japanese Pharmacopoeia Latest edition JP 16 (2011) issued by Pharmaceuticals and Medical Devices Agency 1951: The International Pharmacopoeia Latest edition 5th Edition (2015) issued by WHO 1964: European Pharmacopoeia Latest edition Ph.Eur. 8th Edition issued by the European Directive for the Quality of Medicines

11. GLOBAL HARMONISATION INITIATIVES

12. International Harmonisation • April 1990 - International Conference on Harmonisation • International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH) • Regulatory authorities and pharmaceutical industry

13. ICH Steering Committee WHO – World Heath Organisation EU – European Union EFPIA – European Federation of Pharmaceutical Industries and Associations MHLW – Ministry of Health, Labour and Welfare, Japan JPMA - Japan Pharmaceutical Manufacturers Association FDA – US Food and Drug Administration PhRMA – Pharmaceutical Research and Manufacturers of America IFPMA – International Federation of Pharmaceutical Manufacturers and Associations Source: ICH website www.ich.org

14. International Harmonisation • Objectives of ICH • Increase international harmonisation of technical requirements. • To improve efficiency of new drug development and registration process. • To promote public health, prevent duplication of clinical trials in humans and minimise the use of animal testing without compromising safety and effectiveness. • Accomplished through the development and implementation of harmonised guidelines and standards.

15. ICH Guidelines Q - Quality; S - Safety; E - Efficacy; M - Multidisciplinary Source: ICH website www.ich.org

16. ICH Outcomes • Over 80 guidelines on technical requirements on: • Efficacy - 9 topics/ 20 guidelines (E3 Structure and content of Clinical Study Reports • Safety - 9 topics/18 guidelines (S1 Rodent Carcinogenicity Studies for Human Pharmaceuticals) • Quality - 10 topics/41 guidelines (Q1A (R2) Stability testing of New Drug Substances and Products

17. ICH Outcomes • MultidisciplinaryGuidelines • Medical dictionary for adverse event reporting and coding of clinical trial data (MedDRA) • Electronic Standards for the Transfer of Regulatory Information • Non clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals – M3 (R2) • Common Technical Document (CTD & eCTD) • Data elements and standards for drug dictionaries – M5

18. CTD organisation in Modules Source: ICH website www.ich.org

19. International Collaboration on GMP inspection • Greater international collaboration and information sharing to help to better distribute inspection capacity allowing more sites to be monitored and reducing unnecessary duplication. • 80% of all active pharmaceutical ingredients (API) used in Europe comes from other countries. • Joint API inspections pilot programme (2008–2010) was a success among the participating authorities • The reference GMP standard for the inspections is ICH Q7 • Sharing of inspection plans and outcomes for such inspections carried out or proposed to be carried out.

20. International Collaboration on GMP inspection • Co-ordination of GMP inspections – Finished Dosage Forms • Coordination of inspections of manufacturers in third countries among EU national competent authorities. • India and China are significant manufacturing sources • 1 in 2 of EU third country inspections are carried out in India and China

21. International Collaboration on GMP inspection The geographical location of the foreign inspections carried out by EEA competent authorities Source: Luigetti R. et al. GMP Oversight of Medicines Manufacturers in the European Union. PDA Letter. Sep 25, 2015

22. International Collaboration on GMP inspection • Malta’s contribution in third-country GMP inspections • March 2014: Malta’s first third-country GMP inspection • To date: Malta has carried out 11 third-country GMP inspections in India and Serbia • Advantages of Malta: • Strategic position • Flexible regulatory authority • Highly Efficient • Professional trained staff

23. International Collaboration on GMP inspection • EMA/FDA inspection programme for finished-dosage-form manufacturers – pilot programme initiative launched in January 2012 • Share work on inspection of manufacturing sites. • This enables the two authorities to rely on each other’s inspection outcomes rather than carrying out separate inspections in duplicate.

24. International Collaboration on GMP inspection • EudraGMDP database to improve sharing of information • Access to all EU and EEA Member States • Several international regulatory partners have unrestricted read and write access to the database including those with mutual recognition agreements. • October 2013 Japanese regulatory authorities were the first to start entering information into this database.

25. Drug Development

26. Shift to Biopharma

27. Biotech – Health care Challenge Big annual cost for biologics

28. Patient access to innovation: Biosimilars Biosimilars is defined as “a biological medicinal product that contains a version of the active substance of an already authorised original biological medicinal product. A biosimilar demonstrates similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise.”1 1. Guideline on similar biological medicinal products. European Medicines Agency. CHMP/437/04 Rev 1. 23 October 2014

29. More than $60 billion worth of patents on biological products are expiring before 2020 This figure shows the number of biosimilars clinical trials started between 2007 and 2014 Source: Boren J. Et al. Challenges in Global Biosimilar Development: A Regulatory Perspective. Contract Pharma June 2015

30. Patent expiration of biologicals Source: Kumar R., Singh J. Biosimilar drugs.. Current status. Int J Appl Basic Med Res. 2014 Jul-Dec; 4(2): 63–66.

31. Biosimilars are not generics This figure shows the differences between small molecule drugs and biopharmaceuticals. Source: Advantage, A. S. H. P. "A Health-System Pharmacist’s Guide to Biosimilars: Regulatory, Scientific, and Practical Considerations." Continuing Education Study Guide. http://ashpadvantagemedia. com/downloads/biosimcentral_guidelines. pdf.

32. Challenges with biosimilars Manufacturing complexity Clinical safety and immunogenicity profile Post marketing pharmacovigilance Establishing biosimilarity Interchangeability and substitution Willingness of physicians, payers and patients to adopt biosimilars Education - pharmacists play an important role

33. Need for harmonisation Simpler communication Sharing of Information Efficiency Variability Access to patients Costs

34. Innovative Medicines Initiative Public private partnership established by the EU and EFPIA Aims to improve pharmaceutical innovation for the benefit of consumers Enhance competitiveness of the health sector in Europe Serve as a European engine for regulatory science To translate scientific results into the regulatory framework at global conferences in order to align regulatory requirements.

35. If you want to go fast go alone If you want to go far go together African proverb

36. Thank You