Transcript Pharmacovigilance obligations of the Pharmaceutical companies in

Pharmacovigilance obligations of the
Pharmaceutical companies in India
Dr.Sumedh M.Gaikwad
MD,DM
Clinical Pharmacology,
Director Medical Services,
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Richter Themis Medicare Ltd.
1/20
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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
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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
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REGULATIONS RELATING TO PV IN INDIA
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Pharmaceutical company & PV System
-In House
-Outsourced to CROs
Schedule-Y
-Define responsibilities of Pharma
company to ensure adequate compliance of
PV obligations
-PMS
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NATIONAL PV PROGRAM
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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
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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
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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
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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.
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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
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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
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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
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 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
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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.
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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.
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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
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PV OBLIGATIONS OF INDIAN
COMPANIES WITH SUBSIDIARIES
ABROAD
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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
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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
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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
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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.
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