What you need to know about the Pharmacovigilance guidelines for companies marketing drugs in India. A concise overview of the six modules in the Guidance Document and the responsibilities of the Marketing Authorization Holders.

1. Pharmacovigilance Guidance
Document – Pharmacovigilance
Programme of India
Himanshu Bhatnagar, MD

2. Background and Overview
• Prepared by the National Coordination Centre (NCC) –
Pharmacovigilance Programme of India (PVPI), Indian
Pharmacopoeia Commission(IPC) under the aegis of the Central
Drug Standard Control Organization (CDSCO)
• CDSCO is under the Directorate General of Health Services (DGHS),
Ministry of Health and Family Welfare (MoHFW). State Drug
Control Organizations (SDCO) are under its purview and
responsible for manufacturing licensing and sale/distribution of
drugs in their respective states
• Causality assessment mandatory for new drugs, not for
subsequently approved drugs

3. Organizational Structure
Ministry of Health and
Family Welfare
Indian Pharmacopoeia
Commission
National
Coordination Centre
- PvPI
Guidance
Document
Directorate General of Health
Services
Central Drug
Standards Control
Organization
State Drug
Control
Organizations
Guidance
Document

4. Background and Overview
• Six Modules –
 I – Pharmacovigilance System Master File (PSMF)
 II – Collection, Processing, and Reporting of Individual Case
Safety Reports (ICSR)
 III – Preparation and Submission of Periodic Safety Update
Report (PSUR)
 IV – Quality Management System (QMS) at the Marketing
Authorization Holder organization
 V – Audit and Inspection of PV System at MAH organization
 VI – Submission of Risk Management Plan (RMP)

5. Module I – PSMF/PvMF
▫ Contains all information related to MAH PV system
▫ PV Officer-in-Charge (PVOI) – similar to QPPV in the EU.
Responsible for the overall PV activities of the MAH –
development of training modules and training of staff, framing
and revision of SOP, establishment and maintenance of QMS.
▫ PSMF shall contain information on MAH PV structure (or CRO
structure and agreement with the same, if outsourced)
▫ Sources of information for ICSR
▫ Details of the process followed for dealing with Adverse Event
(AE) reports

6. Module I – PSMF/PvMF
▫ Details of compilation and preparation of PSUR
▫ Details of drug safety related communications to public/health
professionals etc.
▫ Product labels and revision history
▫ All active SOP relevant to the PV processes should be included
▫ Details of the QMS – soft copy of all PV documents to be retained
indefinitely, hard copies for 10 years, a logbook for recording primary
information for every AE reported, any Corrective and Preventive Action
(CAPA) resulting from internal or external audits
▫ Evidence of monitoring of the PV system performance

7. Module II – Collection, Processing, and
Reporting of ICSR
▫ Sources of information include – solicited reports (clinical trials, non-
interventional studies, patient support programmes, and patient or
healthcare provider surveys etc.), spontaneous reports
(patients/doctors/nurses/pharmacists), literature, contact
email/helpline reports, medical information queries, reports from
internet/digital media, and reports from CDSCO etc.
▫ Valid reports to have four elements – identifiable reporter, identifiable
patient, suspect drug, and an adverse event
▫ All ICSR to be submitted to NCC-PvPI, IPC in E2B, xml format
▫ AE coding to use ADR coding dictionary ; disease coding to follow ICD
▫ What’s missing – Clarification on which ADR coding dictionary is to be
used, thought the assumption is that it will conform to UMC protocols

8. Module II – Collection, Processing, and
Reporting of ICSR
▫ Timelines – All serious AE/ADR, expected or unexpected to
be reported to HA within 15 days of receipt; all non-serious
AE/ADR to be reported within 30 days
▫ WHO-UMC Causality Assessment Scale to be used for
causality assessment (not mandatory). Causality
assessment is mandatory for new drugs
▫ Follow-up information should be solicited where possible,
especially in AE reported in special populations (pregnant
women, children, old patients).
▫ What’s missing - No guidance on how many attempts to be
made

9. Module III – Preparation and
Submission of PSUR
▫ PSUR to be submitted to the NCC-PvPI, six-monthly for the
first 2 years and annually for the next 2 years. Subsequent
PSUR submission may be necessary if CDSCO decides so,
based in the benefit-risk profile of the drug
▫ One PSUR to cover all formulations, dosage forms, and
indications
▫ Only interval data to be included
▫ PSUR to be submitted within 30 days of the last day of the
reporting period
▫ ICSR reporting guidelines to remain in force

10. Module III – Preparation and
Submission of PSUR
PSUR Structure
1. Title Page
2. Introduction
3. Current worldwide marketing authorization status
4. Update of actions taken for safety reasons
5. Changes to Reference Safety Information like PIL,
CCDS & SmPCs
6. Estimated patient exposure
 6.1 Cumulative subject exposure in clinical trials
 6.2 Cumulative and interval patient exposure from marketing
experience in India
 6.3 Cumulative and interval patient exposure from marketing
experience from rest of the world

11. Module III – Preparation and
Submission of PSUR
PSUR Structure
7. Presentation of individual case histories
 7.1 Line listing of individual cases received from India
 7.2 Line listing of individual cases received from rest of the World
 7.3 Cumulative summary tabulations of SAES from clinical trials
 7.4 Cumulative and interval summary tabulations from Post-
Marketing data sources
8. Studies
 8.1 Summaries of significant findings from clinical trials during
the reporting period
 8.2 Findings from non-interventional studies
 8.3 Information from other clinical trial sources
 8.4 Findings from non-clinical studies
 8.5 Findings from literature

12. Module III – Preparation and
Submission of PSUR
PSUR Structure
9. Other Information
 9.1 Lack of efficacy in controlled clinical trials
 9.2 Late-Breaking Information
 9.3 Overview of Signals: New, Ongoing, or Closed
10. Overall Safety Evaluation
 10.1 Signal and Risk Evaluation
 10.2 Benefit Evaluation
 10.3 Benefit-Risk Analysis Evaluation
11. Conclusions
12. Appendix to the PSUR

13. Module IV – Quality Management
System (QMS)
▫ Mandatory for all MAH to ensure:
 Adequate trained personnel
 Adequate training to the personnel
 Adequate records of the training material/SOP
 Version control to ensure outdated versions are not in use
▫ Internal audits to ensure the PV system is running smoothly, investigation, CAPA
and records of actions taken for any noted real/potential shortcomings
▫ Soft copies of all documents to be kept indefinitely, hard copies for a minimum of
10 years
▫ Business Continuity Plan in place
▫ Data back-up systems
▫ Performance indicators to monitor the performance of PV systems (not
mandatory)

14. Module V – Audit and Inspection of PV
System at MAH organization
▫ HA can conduct audit/inspection of MAH PV systems
▫ Routine inspections and ad hoc inspections (due to specific safety concern for one
or a few specified products)
▫ Ad hoc (for cause) inspections – triggered by poor reporting quality of
ICSR/aggregate reports, non-compliance with HA requests, issues with CAPA
implementation etc
▫ Audits of entities to whom the PV work is outsourced can also be performed
▫ Includes inspection of documents and interview with PV personnel. No clarity on
whether the list of such personnel will be ad hoc or pre-decided by the HA or the
MAH (alone or acting in concert)
▫ What’s missing – No guidance on frequency of routine inspections or period of
prior notice.

15. Module V – Audit and Inspection of PV
System at MAH organization
▫ Inspection findings can be:
 Critical – fundamental weakness that can impact patient safety or
pose a risk to public health
 Major – significant weakness in one or more PV processes that can
impact patient safety or public health
 Minor – weakness in one or more PV processes that is unlikely to
impact patient safety or public health
▫ MAH to prepare a CAPA following sharing of the audit/inspection
findings. HA oversight to continue until CAPA is completed
▫ Regulatory actions (decided on a case-to-case basis) can include –
 Suspension/cancellation of marketing authorization
 Restriction on new marketing authorization applications
 Product recall
 Label update etc

16. Module VI – Risk Management Plan
▫ Identifies and characterizes the known safety profile of the
drug
▫ Indicates means for further characterization of the profile,
including potential risks and missing information
▫ Describes measures to minimize risks associated with use
of the drug, and methods to measure the effectiveness of
the same
▫ Documents post-marketing obligations imposed while
obtaining marketing authorization

17. Module VI – Risk Management Plan
▫ Components of the RMP
 Pharmaceutical product overview
 Safety specifications
 2.1 Epidemiology of the indication/target population(s)
 2.2 Non-clinical information
 2.3 Clinical trial exposure
 2.4 Populations not studied in clinical trials
 2.5 Post-marketing experience
 2.6 Identified and Potential risks
 2.7 Summary of Safety concerns
 2.8 Risk minimization activities

18. For more information – himanshubhatnagar@gmail.com,
https://www.linkedin.com/in/himanshu-bhatnagar-101a44129/