1. Anthony Serracino Inglott Chairman of the Malta Medicines Authority
203,Level 3,
Rue D’Argens,
Gzira,GZR 1368
Tel: (+356)
Fax: (+356)
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 sciences expenses
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 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

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

16. ICH Outcomes Over 80 guidelines on technical requirements on:
Efficacy - 9 topics/ 20 guidelines (E3 Structure and content of Clinical Study Reports
Safety 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 Multidisciplinary Guidelines
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

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 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 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. 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. Simpler communication Sharing of Information
Need for harmonisation
Simpler communication
Sharing of Information
Variability
Efficiency
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