1. ROLE OF THE PHYSICIAN IN THE APPROVAL PROCESS Stephanie de Bono MD PhD Medical Advisor, Eli Lilly

2. MISSION STATEMENT The mission of the Faculty is to advance the science and practice of pharmaceutical medicine by working to develop and maintain competence, ethics and integrity and the highest professional standards in the specialty for the benefit of the public

3. Your Primary Duty of Care is to the Individual Patients & Research Subjects Come First Product Loyalty Academic Funding Investor Loyalty Employee Loyalty Shareholder Loyalty Patient First! Regulator Labeling Self Interest FPM Ethical Issues Subcommittee 2008

4. OPENING STATEMENTS There is no legal requirement to have a physician in the approval process The UK has a tradition of using Pharmaceutical Physicians (PPs) but this is not necessarily reproduced in other countries. Many regulatory assessors will be medics

5. GOOD PHARMACEUTICAL MEDICAL PRACTICE Pharmaceutical Physicians play a key role in patient care by – Having a thorough understanding of the key therapeutic areas in which they work – Designing clinical research programmes and protocols in areas of medical need working to the relevant guidelines – Ensuring that they fulfil their obligations in clarifying, evaluating and reporting adverse events

6. GPMP contd – Ensuring that documents submitted to the regulatory authorities accurately reflect the data that has been collected – Ensuring that relevant data are made available for publication (ABPI Code Clause 21.3) – Ensuring that the data in the SmPC is consistent with the Marketing Authorisation – Ensuring that PILs are clear and can be understood by the end user – Ensuring that all promotional material and rep product training is consistent with the SmPC

7. CLINICAL PHARMACOLOGY Contribute to investigations, judgements and decisions on the clinical pharmacology of a medicine in all phases of its R&D. Apply this knowledge in – Continuing support and extension of the clinical indications, formulations and dosage schedules – Investigation and assessment of suspected ADRs – Submissions to regulatory authorities – Developing product information

8. CLINICAL PHARMACOLOGY contd Duff Report 2006 following TGN 1412 trial called for validated higher qualifications in Human Pharmacology FPM has introduced the Diploma and Certificate in Human Pharmacology

9. CLINICAL RESEARCH Protocols must be designed to answer genuine scientific questions The protection of participants must take precedence over scientific interest Suspected research misconduct must be reported to the MHRA (Regulation 29A of the Medicines for Human Use (Clinical Trials) Regulations 2004 [SI 2004/1031] as amended by SI 2006/1928)

10. CLINICAL RESEARCH contd National Research Ethics Service (NRES) encourages attendance at relevant REC meeting by sponsor and/or chief investigator Health Research Authority (HRA) - new UK single research regulator Currently interim Authority responsible for NRES

11. STATISTICS AND DATA MANAGEMENT Contribute clinical input to enable effective collaborative work with professional statistical and data management staff ensuring – Optimal study design, – Effective management – Effective analysis – Effective reporting of clinical trial data

12. WRITING REPORTS PPs usually responsible for writing key clinical sections of final study reports. They must stand by the principles that all relevant reports should be published Safety reporting is a key tool in the protection of the public. PPs must never allow commercial interests to prevent such reporting

13. NEW PHARMACOVIGILANCE REGULATION European regulation (1235/2010), Directive (2010/84/EU) 31/12/10 Regulation applies from 2/7/12 Directive came into force on 20/1/11 and must be in MS legislation by 21/7/12 Definition of ADR amended to cover noxious and unintended effects resulting from medication errors and off-label use

14. NEW PHARMACOVIGILANCE REGULATION contd Key factors – Importance of risk management plans for new products – Improves the legal basis of post authorisation studies – Improves the transparency of data

15. NEW PHARMACOVIGILANCE REGULATION contd The MAH must have permanently and continuously at its disposal an appropriate QPP. If that QPP isn’t a medic, he/she must have permanent access to a medical practitioner The MAH must provide all available information including the results of clinical trials and data from the use of the medicine outside the terms of the MA

16. ABPI CODE 2011 Clause 14.1 – no longer required for a medic to sign off promotional material Clause 14.3 – a registered medical practitioner is required to sign off material relating to – Education for the public/pts – Working with patient organisations – Joint working with the NHS – Patient support programmes

17. ABPI CODE contd Clause 21.2 – The scientific service must include a registered medical practitioner who will be responsible for non-interventional studies

18. WORKING IN TEAMS Understand your own limitations of knowledge and when to involve others PPs who have managerial responsibility for colleagues will ensure that they are adequately trained for their job function

19. CONCLUSIONS Remember your prime objective is to benefit patients Read the FPM Guiding Principles for Pharmaceutical Physicians and treat them as your ethical Code of Practice (www.fpm.org.uk)