Report on. CDSCO-WHO-EU In-Country Workshop for. Pharmacovigilance Inspections for Central & State. Regulators and other Stakeholders In India, from

Transcription

1 Report on CDSCO-WHO-EU In-Country Workshop for Pharmacovigilance Inspections for Central & State Regulators and other Stakeholders In India, from 16 th to 20 th April 2018 at Hotel Lalit, New Delhi

2 Table of Contents Sr no Content Page no 1 Agenda Background Summary Outcome 16 5 Annexure List of Participants Page 1 of 18

3 Page 2 of 18

4 Agenda Day 1 Monday S. No. Start Time End Time Activity/Module Speakers 1 08:30 09:30 Registration 2 09:30 10:30 Opening/Welcome Address Dr. S. Eswara Reddy, Drugs Controller General (India), Ministry of Health & Family Welfare, Government of India Background and Expectations Special Address Inaugural Address Dr. Madhur Gupta, Technical Officer- Pharmaceuticals, WHO Country Office for India Mr. Wojciech Dziworski, European Union, Delegation to India Dr. V. G. Somani, Joint Drugs Controller India, Ministry of Health & Family Welfare, Government of India 3 10:30 10:45 Ice Breaker 10:45 11:00 Tea Break 4 11:00 11:30 Pre Assessment 5 11:30 13:00 Module 1-Introduction To PV Inspections 13:00 14:00 Lunch 6 14:00 15:00 Module 2- Risk Management Approach To PC Inspection Programme Dr. K. Bangarurajan, Joint Drugs Controller India, Ministry of Health & Family Welfare, Government of India Dr Madhur Gupta, WHO India Dr Viola Sarinic Macolic, WHO HQ Geneva Mr Somnath Basu, CDSCO 15:00 15:30 Tea Break 7 15:30 17:00 Continue with Module 2 Dr Viola Sarinic Macolic, WHO HQ Geneva 8 17:00 17:30 Evaluation of The Day Day 2 Tuesday S. No. Start Time End Time Activity Speakers 1 09:00 09:30 Warm Up/ Programme Of The Day 2 9:30 10:45 Module 3 Planning For Inspection Facilitators Dr. Nele Matthijs, EU Page 3 of 18

5 10:45 11:00 Tea Break 3 11:00 13:00 Module 3 Planning For Inspection 13:00 14:00 Lunch 4 14:00 15:30 Module 4 Conducting An Inspection 15:30 15:45 Tea Break 5 15:45 17:00 Module 4 Conducting An Inspection 6 17:00 17:30 Evaluation Of The Day Day 3 Wednesday Dr. Porcelli Paolo, EU Dr. Nele Matthijs, EU Dr. Porcelli Paolo, EU S. No. Start Time End Time Activity Speakers 1 09:00 09:30 Warm Up / Programme Of Facilitators The Day 2 09:30 10:45 Module 5 Taking Decision Dr. Nele Matthijs, EU 10:45 11:00 Tea Break 3 11:00 13:00 Module 5 Taking Decision Dr. Porcelli Paolo, EU 13:00 14:00 Lunch 4 14:00 15:30 Module 6 Follow-Up Actions Dr. Nele Matthijs, EU 15:30 15:45 Tea Break 5 15:45 17:00 Module 6 Follow-Up Actions Dr. Porcelli Paolo, EU 6 17:00 17:30 Evaluation of the Day Day 4 Thursday S. No. Start Time End Time Activity Speakers 1 09:00 17:30 Programme of the Day and Facilitators Travel to the Mock Audit Site Day 5 Friday S. No. Start Time End Time Activity Speakers 1 09:00 09:30 Warm Up/ Programme of Facilitators The Day 2 09:30 10:45 Module 7 Mock Up Participants Inspection: Presentations And Reflection 10:45 11:00 Tea Break 3 11:00 13:00 Module 7 Mock Up Participants Inspection: Presentations And Reflection 13:00 14:00 Lunch 4 14:00 15:30 Reflections of Experts for Experts Mock audit presentations 15:30 15:45 Tea Break 5 15:45 16:15 Post Assessment 6 16:15 17:30 Certificates and Closure Page 4 of 18

6 Background The Central Drug Standard Control Organization (CDSCO) acting as national regulatory authority (NRA). A WHO led team of international experts conducted the NRA Re-benchmarking in February They concluded that CDSCO and affiliated institutions meet WHO published indicators for a functional regulatory system for vaccines, indicating that the country s vaccine manufacturers remain eligible to apply for prequalification of their products. During the aforementioned rebenchmarking, the institutional development plan (IDP) and the road map for NRA strengthening in India were developed to address the identified gaps. Further as per recommendations of NRA Assessment to strengthen National Regulatory System (sub -indicator RS06.01) to upgrade skill & competency of staff through trainings & workshops CDSCO has planned trainings as per IDP. One of the recommendations of the Vigilance function IDP was to conduct in country capacity building workshop for pharmacovigilance inspections in India for regulators, pharmacovigilance programme staff, AEFI Secretariat and immunization programme amongst key stakeholders. Strengthening of Pharmacovigilance activities and ensuring patient safety has been enforced by CDSCO continuously. Requirements for the Pharmacovigilance have been there as a part of conditions to permissions issued to the applicants eg. new drug permissions, registration certificate eg., Condition no.05 of Form 45 (permission for import of new drugs) and Form 46 (permission for manufacture of new drug) requires PSUR submission and Condition 4 in Form 41 (Registration Certificate for import of Drugs into India) which requires the manufacturer or his authorized agent in India shall inform the licensing authority in the event of any administrative action taken due to adverse reaction. Further, Para 28 of part 1 of Schedule M of Drugs and Cosmetics Rules, 1945 states that the serious adverse reaction should be reported to licensing authority by the licensee. Government of India vide notification no GSR 287(E) also published on 8 March 2016 to amend Schedule Y of the Drugs and Cosmetics Rules, As per the amendment for post marketing surveillance the applicant should have a Pharmacovigilance system in place. In order to encourage active surveillance it is proposed to carryout inspections of the Pharmacovigilance system of the applicants. Further, CDSCO, Indian Pharmacopoeia Commission and the Ministry of Health and Family Welfare have published vaccine guidance documents like Pharmacovigilance Guidance Page 5 of 18

7 Document for the Market Authorisation Holders for Pharmaceutical Products, Guidance for Industry on Pharmacovigilance Requirements for Biological Products, Adverse Events following Immunization-surveillance and response operational guidelines etc. India has a well-established Pharmacovigilance programme of India (PvPI) with the national coordination center at Indian Pharmacopoeia Commission (IPC), Ghaziabad. Further National Coordination Center established 250 ADR monitoring centers throughout the country. Objective 1. To train inspectors, and other stakeholders and start implantation of PV inspection to verify the outcome of GSR 287(E) 2. To conduct a mock audit in a medicines/vaccines facility with the regulators and the experts, for regulatory inspection skills building. Summary The workshop on Pharmacovigilance Inspections for Central & State Regulators and other Stakeholders in India at Hotel Lalit, New Delhi was from th April/2018 organized by CDSCO in collaboration with WHO and EU. The participants included 46 Drugs Inspectors from CDSCO HQ, Zonal/Sub-zonal offices and from state drugs authority including participants from AEFI division of Ministry of Health and Family Welfare and PvPI division of IPC. The speakers included experts from CDSCO, WHO, EU and PvPI. Session wise Proceedings Inaugural Session: 1. Dr. S. Eswara Reddy, Drugs Controller General of India Dr. S. Eswara Reddy, DCG (I) welcomed all the dignitaries, speakers and participants to the training programme. He appraised the participants that a strong Pharmacovigilance system amongst all the stakeholders would contribute to patient safety. He put forth the importance of knowledge up- gradation and emphasis on science based decision making. DCG (I) informed the participants that PvPI has been declared as WHO collaborating centre for Pharmacovigilance in public health programmes and regulatory services. He wished the participants success in the programme. Page 6 of 18

8 He emphasized on the importance of Pharmacovigilance strengthening in India especially from the perspective of patient safety. He told the participants that establishing safety of the drug after its approval can be achieved effectively only if all the stakeholders like MAHs have a robust system in place. He said that the training has been designed to make the participants aware on the Drugs and Cosmetics Rules on Pharmacovigilance, expectations from stakeholders, roles of various partners like PvPI, AEFI Secretariat, WHO and MAHs etc. The inspectors of CDSCO should make a concentrated effort to improve the Pharmacovigilance system. He concluded by thanking WHO/EU for organizing this programme & to support for such kind of programme in future. 2. Dr. V G Somani, Joint Drugs Controller of India Dr. V G Somani, JDC (I) welcomed the experts and participants and conveyed his best wishes to them. He further added that the objective of the training is to train the regulators for Page 7 of 18

9 pharmacovigilance inspection. The workshop will impart the basic information to regulators on how to conduct the Pharmacovigilance inspection. 3. Dr. K. Bangarurajan, Joint Drugs Controller of India Dr. K. Bangarurajan, JDC (I) welcomed the experts and participants and thanked WHO and EU for conducting such a workshop which will train the Indian regulators to plan and conduct and even what the Pharmacovigilance inspection basically means. He had put light on the GSR which became effective from 2016 which speaks that every MAH should have the PV system in place. Concluding his speech he told that the workshop will train the regulators about PV inspections. Page 8 of 18

10 Monday, 16 th April, Dr. Madhur Gupta, Technical Officer- Pharmaceuticals, WHO India, presented Introduction to Pharmacovigilance Inspections Summary of the Presentation Dr. Madhur Gupta spoke on WHO Global Benchmarking Tool and the recent achievement of India in the NRA assessment Pharmacovigilance was one of the core functions in the WHO global NRA benchmarking tool. She defined the Good Pharmacovigilance Practices (GVP) as a set of measures drawn up to facilitate the performance safety monitoring of drugs and also explained about the principle of Good Pharmacovigilance Practices. She also focused on the Pharmacovigilance guidance document for MAH briefing the Modules and emphasized on Module-5 i.e., Audit and Inspections of Pharmacovigilance System at MAH Organization. During the presentation she also explained about the Risk Management Plan the primary aim and focus, content of it to the participants.. Page 9 of 18

11 2. Mr. Somnath Basu, Assistant Drugs Controller (India)-CDSCO India, shared views on Risk Management Approach To PV Inspection Programme Summary of Presentation Mr. Somnath Basu spoke on the Risk Management Approach to PV Inspection Programme. He has given the overview on the historical background on the ADR monitoring system establishment in India. Further he has discussed neatly about the difference between adverse drugs reaction and side effects and also explained about the types of ADR. He further explained about the Gazette notification GSR 287 (E) dated 08/03/2016 and explained about the major amendment done in Schedule Y to the participants. He has also shown the screenshot of CDSCO published Guidance for MAHs (importers/ manufacturers). 3. Dr. Viola Sarinic Macolic, WHO HQ Geneva has also focussed on Introduction to Pharmacovigilance Inspections and Risk Management Approach to PV Inspection Programme in her presentation Summary of Presentation Dr. Viola Sarinic Macolic gave details about the Introduction to Pharmacovigilance Inspections and Risk Management Approach To PV Inspection Programme in her presentation During the introduction of PV inspection emphasis was laid on the quality and the quality product. While explaining the system she briefly explained about the system and what is it. Page 10 of 18

12 Further she focussed on overall quality objective and principle of PV system. She spoke on risk management and the main goal for conducting a GVP inspection i.e., to determine whether a MAH complies with the PV obligations prescribed by the applicable national legislation & guidelines. Type of PV inspection was explained by her and active involvement of participant was there while solving the case study for classifying the example with respect to the type of inspection given by her. Pre-assessment of the participants was conducted during the session. Page 11 of 18

13 Tuesday, 17 th April, Dr. Vivek Kalaiselvan, Principal Scientific officer, PvPI explained on Pharmacovigilance System in India Summary of Presentation He briefed about the start-up of national coordination centre and WHO collaborative centre. He further explained about the Gazette notification GSR 287 (E) dated 08/03/2016 and explained about the major amendment done in Schedule Y to the participants. He also focused on the Pharmacovigilance guidance document for MAH He concluded his presentation giving stress on points such as Availability of Prescription Information Leaflet, Training on Good PV practices to the stakeholders, PV audit/inspection, and Compliance of Good PV practices. 2. Dr. Nele Matthijs, & Dr. Porcelli Paolo shared views on Planning and conducting Pharmacovigilance Inspection Summary of Presentation Dr. Nele Matthijs, & Dr. Porcelli Paolo spoke on the Planning and conducting Pharmacovigilance Inspection. He spoke about the procedure for Market Authorization i.e., Centralized, Decentralized and Mutual Recognition. Dr. Paolo focused on Union procedures for inspections. He told about the project of an European Medicine Agency on-line PhV inspectors basic training course its aims & objectives of the course and techniques to conduct the inspection. Dr. Nele has laid emphasis on the PV legislations and Guidance reference and what is the need for Pharmacovigilance inspection and how to perform it. She also laid emphasis on four element for performing the inspection i.e., preparation, conducting, reporting and succession. She also briefed the document to be reviewed and planning of inspection using risk based approach. She explained the participants about what question to be asked during the inspection and Page 12 of 18

14 also about the importance of MedDRA and the detailed about the information captured in it. Wednesday, 18 th April, Dr. Nele Matthijs, & Dr. Porcelli Paolo shared views on Taking decision and follow-up action Summary of Presentation Dr. Paolo has focused on the EU detection & Management Procedures and about the risk management plan. Dr. Nele Matthijs explained about the different types of PV inspections and has shown the examples for the finding/deficiencies and put the light on the categorization of the findings i.e., critical, major and minor. In relation to the inspection of contract sites she explained that there should be clear responsibilities of both parties in contract. Thursday, 19 th April, 2018 Mock audit at the PV site of M/s. Sun Pharmaceuticals ltd was conducted on Day 4. Two groups were formed. One group was headed by Dr. Nele Matthijs, and Mr. Somnath Basu and other by Dr. Porcelli Paolo and Dr. Madhur Gupta having one group leader in each group along with the officials from CDSCO and other stakeholders. The team has attended the presentation given by the company on Pharmacovigilance Quality Management System, Pharmacovigilance SOPs & CAPA management, Argus Safety overview, Clinical Trial and Post-marketing ICSR processing, Medical and expedited review of ICSRs, PSURs, Signal management for marketed and international products and reviewed the documents. Agenda for the mock audit: S. No. Venue: Raman Room, Ground Floor, R&D 3 Building, Sun Pharmaceutical Industries Ltd, Research & Development Center, Sarhaul, Sector 18, Gurugram , Haryana (India) Topic Time Groups Speaker 1. Welcome and Overview of Pharmacovigilance at Sun Pharma 10:00 10:10 I and II Rajinder K Jalali 2. Pharmacovigilance Quality Management System 10:10 10:20 I and II Shri Prakash Singh Page 13 of 18

15 3. Pharmacovigilance SOP & CAPA management 10:20 10:30 I and II 4. Periodic Safety Update Reports 10:30 I and II 10:40 5. Open Q and A Tea/Coffee Break (11:00 11:20) at Pre-function Area For Group-I 6. Argus Safety overview 11:20 I 11:30 System/Documents Review 11:30-11:50 7. Clinical Trial and Post-marketing ICSR 11:50 I processing 12:00 System/Documents Review 12:00-12:20 8. Medical review of ICSRs 12:20 I 12:30 System/Documents Review 12:30-12:50 9. Expedited reporting of ICSRs 12:50 I 13:00 System/Documents Review 13:00-13:20 Lunch Break (13:20 14:00) at Pre-function Area 10. Overview of Aggregate Data Analysis 14:00 I 14:10 System/Documents Review 14:10-14: US Periodic Adverse Experience Reports 14:30 I 14:40 System/Documents Review 14:40-15: Signal Management for Marketed Products 15:00 I 15:10 Shri Prakash Singh Sachin Nain Rajiv Maini A Murugan Deepak Kumar Singh Devesh Mishra Ankur Arora Varun Thapar Shilpa Sharma System/Documents Review 15:10-15:30 Tea Break (15:30 16:00) at Pre-function Area 13. Signal Management for Investigational 16:00 I Onkar Singh Page 14 of 18

16 Products 16:10 System/Documents Review 16:10-16:30 For Group-II 14. Overview of Aggregate Data Analysis 11:20 11:30 II System/Documents Review 11:30-11: US Periodic Adverse Experience Reports 11:50 II 12:00 System/Documents Review 12:00-12: Signal Management for Marketed Products 12:20 II 12:30 System/Documents Review 12:30-12: Signal Management for Investigational 12:50 II Products 13:00 System/Documents Review 13:00-13:20 Lunch Break (13:20 14:00) at Pre-function Area 18. Argus Safety overview 14:00 II 14:10 System/Documents Review 14:10-14: Clinical Trial and Post-marketing ICSR 14:30 II processing 14:40 System/Documents Review 14:40-15: Medical review of ICSRs 15:00 II 15:10 System/Documents Review 15:10-15:30 Tea Break (15:30 16:00) at Pre-function Area 21. Expedited reporting of ICSRs 16:00 II 16:10 System/Documents Review 16:10-16:30 21 Closing Meeting 16:30-17:00 Ankur Arora Varun Thapar Shilpa Sharma Onkar Singh Rajiv Maini A Murugan Deepak Kumar Singh Devesh Mishra I and II - Page 15 of 18

17 Friday, 20 th April, 2018 The day was started with the post assessment of the participants. Both the groups have been provided the time for the preparation of presentation for mock audit. Based on the review of the documents the team has given the presentation about the objective, scope of mock audit including their experience during review of documents and systems related to Pharmacovigilance. The team also shared the observation made during mock audit. Outcomes of Training The training programme was designed to impart comprehensive knowledge to CDSCO and State inspectors on the legal provisions on Pharmacovigilance, vaccine national guidelines, international practices and the knowledge on actual framework of Pharmacovigilance with the market authorization holders, in line with Good Pharmacovigilance Practices. Further it was also observed from the mark of Pre and Post assessment that the participants were benefited from this workshop. This workshop has prepared all the participants for Pharmacovigilance inspection in line with Good Pharmacovigilance Practice. The graphical presentation for the marks of participants secured during pre and post assessment: Pre post 0 Page 16 of 18

18 Annexure Annexure I: List of Participants Sr CDSCO HQ/ Zonal/Sub- Name Designation # Zonal Office 1. Sh. N.K.Jayasenthil Drugs Inspector CDSCO, HQ 2. Sh. Sachin Kapse Drugs Inspector CDSCO, HQ 3. Sh. Satish Sangale Drugs Inspector CDSCO, HQ 4. Sh. Lokesh Choure Drugs Inspector CDSCO, HQ 5. Sh. Kumara Swamy Dornala Drugs Inspector CDSCO, HQ 6. Sh.Mahaveer Singh Drugs Inspector CDSCO, HQ 7. Sh. Vishal Kachare Drugs Inspector CDSCO, HQ 8. Smt. Heema Naik Drugs Inspector CDSCO, HQ 9. Sh. Shoeb Bismilla Khan Drugs Inspector CDSCO, HQ 10. Sh. Debashish Nayak Drugs Inspector CDSCO, HQ 11. Sh. Mukesh Kumar Drugs Inspector CDSCO, HQ 12. Sh. Mahesh Kumar Saini Drugs Inspector CDSCO, HQ 13. Sh. Devendra Pratap Singh Drugs Inspector CDSCO, HQ 14. Sh. Dinesh Drugs Inspector CDSCO, HQ 15. Sh. Dhayalamurthi Siva Drugs Inspector CDSCO, HQ 16. Sh. Kalicharan Drugs Inspector CDSCO, HQ 17. Sh. Dilip Kumar Drugs Inspector CDSCO, North Zone Ghaziabad 18. Sh. Sri Babu Drugs Inspector CDSCO, North Zone Ghaziabad 19. Sh. Saurabh Garg Drugs Inspector CDSCO,Ahmadabad Zone 20. Sh. Manish Nikara Drugs Inspector CDSCO, Ahmadabad Zone 21. Sh. Amol Eknath Kandekar Drugs Inspector CDSCO, West Zone Mumbai 22. Sh. Hemant Madhukar Patil Drugs Inspector CDSCO,West Zone Mumbai Page 17 of 18

19 23. Sh.Ravindra R. Shripad Drugs Inspector CDSCO, JNPT Sea Port Mumbai 24. Smt. Sudarmathi S. Drugs Inspector CDSCO, Sub Zone, Bangalore 25. Smt. Shyamla Devi D. Drugs Inspector CDSCO, Sub Zone, Bangalore 26. Sh. Jay Jyoti Roy Drugs Inspector CDSCO Hyderabad Zone 27. Smt. Sunita Joshi Drugs Inspector CDSCO Hyderabad Zone 28. Sh. Shyam Narayan Singh Drugs Inspector CDSCO Kolkata Zone 29. Sh. Dharmendra Pandey Drugs Inspector CDSCO Kolkata Zone 30. Sh. Basant Kumar Yadav Drugs Inspector CDSCO, Sub Zone Indore 31. Sh. Rahul Singh Drugs Inspector CDSCO, Sub Zone Indore 32. Sh. Kaviyarashan V Drugs Inspector CDSCO, Sub Zone Baddi 33. Sh. Ankur Bansal Drugs Inspector CDSCO, Sub Zone Baddi 34. Sh. Deepak Kumar Drugs Inspector CDSCO, Sub Zone Goa 35. Sh. Surender Kumar Kaswan Drugs Inspector CDSCO, Sub Zone Goa 36. Sh. N. Rajesh Kumar Sr.Drugs Inspector DCA Tamil Nadu 37. Sh. Shashindra Kumar Rajak Drugs Inspector FDA, Madhya Pradesh 38. Sh. Yogesh Gupta Drugs Inspector FDA, Madhya Pradesh 39. Sh. Deepak Sharma Drugs Inspector Drugs Control Department, 40. Delhi Sh. Swapnil Ganjidhar Patil Drugs Inspector Drugs Control Department, Delhi 41. Sh. P. Hanumanna Drugs Inspector DCA, Andhra Pradesh 42. Sh. K. V. Bhupesu Drugs Inspector DCA, Andhra Pradesh 43. Dr. Sudhir Kumar Drugs Inspector DCA, Uttarakhand 44. Dr. Jayesh V. Patel Sr. Drugs Inspector FDCA Gujarat 45. Sh. A.K. Thakre Drugs Inspector FDA, Maharashtra 46. Dr. A.M Manikrao Drugs Inspector FDA, Maharashtra Mr. Vipin Sharma Mr. G Naveen Chandu Patient Safety Senior Pharmacovigilance Associate Patient Safety Senior Pharmacovigilance Associate PvPI PvPI 49. Dr.Nidhi Technical Officer AEFI Page 18 of 18