Pharmacovigilance obligations of the Pharmaceutical companies in India Dr.Sumedh M.Gaikwad MD,DM Clinical Pharmacology, Director Medical Services, Richter Themis Medicare Ltd. 1/20 Themis Medicare Ltd. Dr.Sumedh M.Gaikwad

Introduction Regulations Relating to PV in India National PV program PV activities for Generic Drugs in India Management of Safety Database Safety Reporting During Clinical Trials PV obligations of Indian Companies with Subsidiaries Abroad Conclusion

Introduction Regulatory decision to approve new drug based on benefit & risk Status of Indian Pharma Market for introduction of new drug Change in scenario Govt. efforts PV obligations Pharma Companies

Regulations Relating to PV in India Pharmaceutical company & PV System -In House -Outsourced to CROs Schedule-Y -Define responsibilities of Pharma company to ensure adequate compliance of PV obligations -PMS

National PV program Nation-wide program (CDSCO) Major functions: -Monitoring of spontaneous ADRs -Review of the PSURs submitted by Pharma companies -Assessing safety information for product label amendments, product withdrawals & suspension. Limited guidance in Schedule-Y & protocol by NPP

PV activities for Generic Drugs in India PV obligations of Generic Company in India: -Collection, monitoring, & reporting of spontaneous adverse reaction reports -Preparation of PSURs -Expectations: *To develop adequate systems & expertise for literature searches, management of safety data, signal detection,& risk-benefit analysis of its marketed products

Spontaneous ADRs Spontaneous reporting of ADRs-an important tool: -to gather safety information required for early signal detection -to conduct risk-benefit analysis of new drugs Schedule-Y specifications -SUSAR: report within 15 days of initial of information & all available clinical information related to reaction - Individual ADRs included in next PSUR & not in an urgent manner Limitations: -Details regarding capture, evaluation & FU of ADRs not addressed * Guidance doc. from ICH E2D referred to develop detailed procedures for handling of spontaneous AEs

Guidance doc. from ICH E2D referred to develop detailed procedures for handling of spontaneous AEs: Procedure includes defining minimum four criteria to validate the adverse reaction reports Collection of relevant info. for spontaneous adverse reactions Handling of the reports received from patients or their relatives Evaluation of the spontaneous ARs, for their seriousness & listedness/expectedness FU of spontaneous ARs reports, minimum FUs required, close out of the case etc.

Management of Safety Database No guidelines available from Indian regulators regarding management of safety data or maintenance & update of Company Core Data Sheet or Safety Information

Current Practice : All the data collected during literature searches, spontaneous adverse event reports, clinical & non clinical studies or from all the sources are collected & saved in the product safety file

Signal Detection: -all the safety data collected should be evaluated -if trend becomes apparent, necessary action should be initiated Problems: -Unique Medical Practices in India -High prevalence of polypharmacy -Pharmaceutical market in India is not well regulated

Problems… -lack of relevant data on spontaneous ADR reports -unavailability of the trained staff for signal detection -lack of the push/drive from the regulatory agency Solution: -Generic drug companies in a country like India should have strong system & expertise for signal detection # Generally, Indian generic companies follow the global updates of the innovator’s label

Periodic Safety Update Reports -Important PV tool design to include safety data on a particular drug from all the sources & geographical regions -DCGI recommends a single PSUR for all dosage forms, formulations & indication for one active substance. -License holders are expected to include summary information along with the critical evaluation of the safety profile of a marketed drug in a light of a new changes during post authorization period.

Formats & reporting in PSURs -Formats provided in Schedule-Y is similar to ICH E2C format Reporting Cycle: - All new products, every 6 months for initial 2 years & then annually for next 2 years - Reports due for a period must be submitted within 30 calendar days from the last day of reporting period.

Safety Reporting During Clinical Trials Sponsors Responsibility Investigators Responsibility Limitations of Schedule-Y : - does not specify rules regarding the reporting of foreign cases from multinational trials -lacks further details on the procedures for unblinding, coding etc -handling of the AEs associated with placebo or comparator drugs

PV obligations of Indian Companies with Subsidiaries Abroad Schedule-Y: do not specify anything regarding the expedited reporting of SAR from other countries Eudralex Volume 9A-Guidelines on PV for Medicinal Products for Human Use, clearly specifies the requirement for reporting of foreign cases & case reports from literature searches

Solution: -Indian companies with subsidiaries in Europe; to establish & maintain the safety databases for their products in India & centralize the PV activities such as *literature searches *generation of CIOMS forms *signal detection * risk-benefit analysis *preparation of PSURs in India & QPPV locally in Europe for regulatory interactions

Conclusion In the past; never a compulsion to have a strong PV system to detect ADR of the marketed drugs Presently; increased interest of Indian regulatory authority for PV activities Limitations: -limited guidance available in Schedule-Y as well as protocol published by the NPP

Conclusion…. Challenges faced by the Pharma companies in India: - Low level of reporting spontaneous ADRs - Lack of training of GPs on drug safety & ADR reporting - Non availability of staff trained in PV - Lack of guidance from the Indian regulatory authority due to the lack of expertise & experience.

Thank You!!