1. Current Regulatory Challenges in conduct of Clinical Trials –India​ ​ ​ Prabhat Kumar November 2014

2. AGENDA Clinical Trial current regulatory framework Current regulatory challenges Background of evolution of current regulatory framework Recommendation of the expert committee Actions from the CDSCO Industries expectations Positive developments….! Way forward

3. Clinical Trials: Current Regulatory Framework 1 Drugs and Cosmetics Act,1940 & Rules,1945 ICMR Ethical guidelines,2000/2006 Indian GCP Guidelines, 2001 National Pharma.Vig. Programme, 2004 Revised Schedule Y (Drugs & Cosmetics Rules), 2005

4. Clinical Trials: Current Regulatory Framework 2 BA/BE Study Guidelines, 2005 Notification on Devices,2005 Amendment to Drugs and Cosmetic Act,2008 Notification on Clinical trial registration, 2009 Amendment to D and C Act, CRO Regn,Sch.Y- 1,2009 Proposed Clinical establishment Bill,2010 Amendments in 2012 and 2013 CDSCO official order/notifications………..

5. Background of evolution of current regulatory framework NHRC orders probe into southern state drug trial scandal – several women were as used as human subject for breast cancer drug trial by a pharmaceutical company. Unauthorised clinical trial of vaccine against cervical cancer were conducted by an NGO on 25,000 minor girls in one of the southern states and in western state.(HPV Vaccine Trial) A government funded hospital in Bhopal was conducting clinical trials on unwitting patients. A Medical College in Indore enrolled children for illegal drug tests for nearly ten years. Health activists are concerned about the way many clinical trials are conducted in this country. There have been a series of incidences involving alleged malpractices in recent past, health minister in last govt. talked in Parliament about patient deaths during clinical trials.

6. Background of evolution……framework.Cont.. Expert Committee by MoH under Dr. Ranjit Roy choudhury Term of reference : To formulate policy and guidelines for –Approval of new drugs including biologicals –Approval of clinical trials including global CTs, BA/BE studies for export –Functioning of the 12 NDACs ( now replaced with SEC and TEC) –To identify experts for the CDSCO –Any other matter related to CDSCO

7. Recommendation of the expert committee Total 25 recommendations were suggested by this committee which includes… CTs can be conducted only at accredited Clinical sites by accredited PIs after approval by accredited ECs. Roster of experts (SEC) from all over India and selection of experts by random tables. Roster of accredited sites from which Pharma co.s can select the Sites and PIs. A technical review Committee to be set up to take uniform, unbiased,final decision on approvals. Audio-visual recording wherever necessary in vulnerable groups. Compensation (Financial) to be paid to legal nominees in case of Death or Disability All SAEs to get equal treated whether due to test drug, placebo or Standard treatment. Provision of Ancillary care during trial period.

8. Actions from the CDSCO CDSCO office released a series of orders (total 14) with regard to requirements for conduct/ approval of clinical trials and new drug approval based on the recommendations of R.R. Committee Report. Which includes mainly……. CT Compensation in case of injury or death discerned at a later stage. Providing Ancillary Care to the Clinical Trial subjects Limiting Number of Clinical Trials an investigator can undertake at a time

9. Action…… continued… Requirement for filing of application to market new Chemical Waiver of CT in Indian Population for approval of New Drugs Requirement for filing of application to market new Chemical Entities

10. Industries expectations Need of the clarity Expectation to have consolidated guidance documents providing the current interpretation of the regulations related to the EC functioning, (similar to USFDA, EMEA etc. )

11. Industries expectations Cont.. Clinical trial liabilities Recently DCGI has been instructing sponsors /CROs to include the wording in ICF that sponsor or CRO will provide complete medical care as well as compensation for the injury. The injury may either arise out of the ‘study’ i.e. as specified in the Protocol and the ICF or may arise out of any act, omission, negligence or misconduct of the CRO or the investigator / institution. Who would primarily be liable to compensate the study subject, whether the sponsor or the CRO or the investigator / institution in connection with the study?

12. Industries expectations Cont.. Access to drugs Another issue that arises is the liability of the sponsor to provide access to drugs and treatment post termination of the trial. Depending upon the study protocol, availability of the drug and stage of the trial, this issue needs to be addressed.

13. Positive developments….! In the recent(Oct14) DIA conference, where some of the regulatory challenges were discussed and thoughts from the stake holders There are upcoming positive changes in the near future in the areas of: Clinical trial conduct: Accreditation will be required for Investigators/Study sites to conduct clinical trials. Accreditation of Ethics Committee/Institutional Review Board to approve/oversee clinical trials.

14. Positive developments….! Conti…… Compensation clause for any injury to subjects participating in trials: This is being re-visited (no compensation for ineffective therapy or adverse events not related to drug, or adverse events for patients in placebo arm are being discussed). Audio-visual recording of informed consent (IC) is being revisited. – Regulatory system: Transparency and possibility of online tracking of regulatory application are being worked up on. – Changes in medical/nursing education system. – Affordable health: Health assurance for all patients at primary health centers; health insurance for secondary/tertiary centers.

15. Way forward There are encouraging sentiments of upcoming positive changes in the regulatory environment will lead to more clinical trial work in India. With the advent of globalization, it is important to adhere to global standards and best practice respecting local norms and value at the same time look at innovative ways to provide affordable healthcare to patients in India. Collaborative work is required between regulators, industry and academia to support innovation. Regulatory frame work must be rational and evidence- based; rather mere opinion based.

16. Over Regulation?

17. Controlled regulation: Win-Win situation !!!

18. DISCLAIMER The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to my organisation, its directors, officers, employees, volunteers, members, committee, or affiliates, or any organization with which the presenter is employed or affiliated.

19. QUESTIONS

20. 谢谢 bedankt tesekkürle Ευχαριστώ takk Dziękuję Shukriyâ kiitos aitäh tack tack ありがとう Danke Obrigada Grazie Muchas gracias 너를 감사하십시요 mange tak díky díky tack så mycket Thank you köszi hvala Ďakujem شكرًا תודה Спасибо Mulţumesc Thank yu salamat salamat faleminderit děkuji vam nandri ధన్యవాదాలు köszönöm köszönöm anugurihiitosumi dhanya-waad dhanya-waad go raibh maith agat Merci Merci ačiû Terima Kasih Many THANKS for YOUR Attention