1. 1 The Increasingly Important Role of US and EU Cooperation in GCP in Europe and Globally Steps toward Harmonization DHHS Secretary’s Advisory Committee on Human Research Protections (SACHRP) Meeting Washington, DC, USA 9 March 2010 Francis P. Crawley Good Clinical Practice Alliance – Europe (GCPA) & Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) fpc@gcpalliance.org

2. The Objectives of Clinical Research 1.To Contribute to Public Health 2.To Contribute to Health Science 3.To Contribute to Economic Development 2

3. 3 Good Clinical Practice A Set of Responsibilities ‘a process that makes all parties to a study responsible for patient safety and study quality’

4. US & EU Objectives in Harmonizing GCP (3 August 2009, Launch of a Bilateral GCP Initiative) 1.To achieve common understandings and practices 2.To share standards and methodologies 3.To share knowledge 4.To share resources 5.To improve human subjects protections 4

5. Challenges to GCP Harmonization 1.The extensive reach of clinical trials 2.The complexity of law and regulation 3.Lack of an internationally agreed code of ethics for human research protections 4.The progress of medical science 5.The lack of appropriately representative platforms 5

6. 6 Current Ethical Challenges to GCP in Clinical Trials (1) The use of control arms (placebo) ‘Standard of care’ Informed consent process Community consultation Individual and community access to research The role & responsibility of ethics committees (IRBs/ECs) Compensation for trial injury Patient/Participant Confidentiality and Privacy Locating phase I, II, and III trials Pharmacovigilance

7. 7 Current Ethical Challenges to GCP in Clinical Trials (2) Medical treatment during the course of research Product availability Sponsorship Liability & Insurance Tissues Stem Cell Research Data Protection Monitoring (DMCs) Data Ownership Proprietary Information/Knowledge Publishing Clinical Trial Information and Results Botanical/Traditional Medicines

8. 8 Dimensions of GCP General Frameworks WHO GCP ICH GCP Regional/Applied Frameworks EU GCP US CFR National/Applied GCP Guidelines China, India, Russia, Singapore, Malaysia, Indonesia, South Korea Argentina, Brazil, Mexico, South America, South Africa, Turkey

9. 9 US Regulations

10. 10 The Development of GCP

11. 11 The Development of GCP

12. 12 Indian GCP - CDSCO ‘A need was, however, felt to develop our own Indian Guidelines to ensure uniform quality of clinical research throughout the country and to generate data for registration for new drugs before use in the Indian population.’ Dr. S.P. Agarwal, Director General of Health Services and Chairman, Drug Technical Advisory Board (DTAB)

13. 13 This GCP is a regulation for the standardization of the whole process of a clinical trial, including protocol design, organizing implementation, monitoring, auditing, recording, analysis, summarization and reporting. Good Clinical Practice of Pharmaceutical Products [SFDA (China) order No. 3, Effective on September 1, 2003]

14. 14 Singapore GCP Guideline ‘The launch of the Singapore Guideline for GCP together with the amendments to the Medicines (Clinical Trials) Regulations [serves] to further enhance the existing ethical and scientific standards of clinical investigations in Singapore.’ Preface, Dr. Chen Ai Ju Director of Medical Services, Ministry of Health

15. 15 EU Directive 2001/20/EC ‘OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use’

16. 16 The Guidance Documents Detailed Guidelines on the principles of good clinical practice in the conduct in the EU of clinical trials on medicinal products for human use Detailed guidance on the application format and documentation to be submitted in an application for an ethics committee opinion on a clinical trial on a medicinal product for human use Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities in the European Union, notification of substantial amendments and declaration of the end of a clinical trial Detailed guidelines on the trial master file and archiving to implement the directive on Clinical Trials on medicinal products for human use Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use Detailed guidance on the European database of Suspected Unexpected Serious Adverse Reactions (Eudravigilance -Clinical Trial Module) Detailed guidance on the European clinical trials database (EUDRACT Database)

17. 17 The Guidance Documents (cont.) Detailed guidelines on inspection procedures for the verification of GCP compliance to implement the directive on Clinical Trials on medicinal products for human use Detailed guidelines on the qualifications of inspectors who should verify compliance in clinical trials with the provisions of Good Clinical Practice for an investigational medicinal product to implement the directive on Clinical Trials on medicinal products for human use Manufacturing and/or Import Authorisation of Investigational Products for Human Use-Contents of the Application Authorization Referred to in Article 13, Paragraph 1 of Directive 2001/20/EC: Requirements to Obtain Authorization and Requirements to Be Met by the Holder of This Authorization Draft Proposal for a Commission Directive…/…/EC Amending 91/356/EEC, Laying Down the Principles and Guidelines of Good Manufacturing Practice for Medicinal Products for Human Use Modifications of Commission Directive 91/356/EEC of 13 June 1991 Laying Down the Principles and Guidelines of Good Manufacturing Practice for Medicinal Products for Human Use (two column informal working document) Volume 4: Good Manufacturing Practices; Annex 13: Manufacture of Investigational Medicinal Products; November 2001

18. United Kingdom The law on clinical trials involving medicines 2004

19. The Belgian Law The law concerning experiments on human persons 1 May 2004

20. The French Law The Law Concerning Public Health Policy 8 August 2004

21. FDA Ruling on GCP for Foreign Clinical Studies Not Conducted Under an IND (Federal Register, 28 April 2008) essentially replacing the rule to follow the Declaration of Helsinki (1989) with Good Clinical Practice 21

22. 22 ICH Good Clinical Practice 1996 2. Good clinical practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects. Compliance with this good practice provides assurance that the rights, safety and well- being of trial subjects are protected, and that the results of the clinical trials are credible.

23. The ICH GCP Structure 3 RegionsUSAJapanEurope 3 Regulatory parties FDAMHWEU 3 Industry parties PHARMAJPMAEFPIA 3 ObserversWHO Drugs Directorate, Health Canada EFTA 6 co-sponsors1 umbrella organization = IFPMA

24. ICH Good Clinical Practice Chapter 1: Glossary Chapter 2: The principles of ICH GCP Chapter 3: IRB/IEC Chapter 4: Investigator Chapter 5: Sponsor Chapter 6: Clinical Trial Protocol and Protocol Amendments Addendum A: Investigator’s Brochure Addendum B: Essential Documents for the Conduct of a Clinical Trial

25. 25 The Role of the Regulatory Authority ?

26. The Way Forward for GCP 1.Further National & Regional Development (e.g., CTTI, The AfroGuide Project) 2.A Broader Scope to Include All Health Research 3.Modernizing Guidance to Meet New Developments (e.g., Registries, Results Publication, DMCs, Insurance, Regulatory Science) 4.Appropriate National, Regional, & International Platforms 5.A Broad and Comprehensive Vision Complimented by Small Steps 26

27. 27 US & EU cooperation in GCP promotes public health at home and abroad. It is our responsibility. fpc@gcpalliance.org