Pharmacovigilance System Master File (PSMF)

Introduction

The Pharmacovigilance System Master File (PSMF) provides a description of the pharmacovigilance system used by the MAHs with respect to pharmaceutical products marketed by them. The PSMF is not a part of the Marketing Authorization (MA) dossier and is maintained independently from the MA.

Scope

The scope of this chapter is to provide guidance for MAHs to create and maintain the PSMF at their site. This describes the different documents to be created, updated, controlled, archived and traceable, whenever required.

Contents of the PSMF

The PSMF should contain all information related to MAH's PV system and cover the following sections:

1. Pharmacovigilance personnel and their responsibilities:

Pharmacovigilance Officer-in-Charge (PVOIC): A qualified and trained personnel should be authorized by the company management as

Pharmacovigilance Officer-in-Charge (PVOIC) with responsibilities for dealing PV activities at MAH's organization.

The PVOIC should be a medical or pharmacy professional trained in the collection and analysis of AE reports. Where the PVOIC is a pharmacy professional, there should be a back-up of medically qualified person for causality assessment, as and when required. The PVOIC shall be responsible for the following:

• Development of training modules and organizing training for staff of PV department;
• Identification of PV activities and framing of SOPs, revision of SOPs;
• Establishment and maintenance of Quality Management System (QMS) of PV department;
• The PVOIC should reside in India and respond to queries of regulatory authorities including PvPI, IPC whenever required. The information related to the PVOIC provided in the PSMF should include:

1. Contact details (Name, address, phone, e-mail)
2. Summary, curriculum vitae with the key information on the role of the PVOIC
3. A description of the responsibilities guaranteeing that the PVOIC has sufficient authority over the PV system in order to promote, maintain and improve compliance
4. Details of Deputy PVOIC; A deputy PVOIC will work in the absence of PVOIC. He/she will discharge all role and responsibilities of PVOI

The qualification of deputy PVOIC will be same as that of PVOIC as mentioned above.

2. Pharmacovigilance Organization Structure

A. Marketing Authorization Holder

The Pharmacovigilance system organogram at MAH organization should be included in the PSMF. The authorized signatory should be clearly indicated. The description of PV system at MAH organization should be provided in PSMF.

B. Contract Research Organization (CRO)

If MAH assigns the responsibilities of PV activities of their pharmaceutical products to any CRO, then the information of the company(ies) including their allied PV departments involved and the relationship(s) between CRO & operational units relevant to the fulfilment of PV obligations should be provided. It should include:

• The PV organizational structure of the CRO showing the organogram of the PV department
• Name & address of the organization, where the PV functions are undertaken such as collection of AEs, ICSRs processing, preparation & submission of PSURs, signal detection, RMP, post-marketing surveillance and management of safety variations
• Delegated activities (contracts and agreements)
• Service providing system (e.g., medical information, auditors, patient support programme providers, study data management etc.)
• Commercial arrangements (distributors, licensing partners, co-marketing
• etc.)
• Technical providers (hosting of computer systems and their validation etc.)

ALSO READ: Pharmacovigilance: Questions and Answers

3. Sources of safety data

The PVOIC will be responsible to collect data, reports, publications related to safety of all pharmaceutical products marketed by the MAH from all sources. The main sources for safety data will be as follows:

• Medical information inquiries
• "Contact us" emails, website inquiry forms and helpline etc.
• Pharmaceutical product market complaints-Receipt, handling and disposal
• MAH employees involved in PV activities
• Spontaneous information from patient or their care givers and follow up of
• information
• Published literature
• Spontaneous reporting by Healthcare Professionals (HCPs)
• Reports from internet, digital media or social media
• Patient-support programmes
• Reports from National Regulatory Authority
• Contract partners involved in PV activities
• Market Research Programmes

4. Pharmacovigilance Processes

A. Description

• A description and flow-diagram of the entire PV process, data handling, records control and archives of PV performance and covering the following aspects should be included in the PSMF
• The procedures for collection, collation, processing, assessment, reporting and follow-up of ICSR
• Compilation of ICSR for the submission of PSURs
• Review of ICSR, signal detection (if any), Drug Safety Alerts, Corrective and Preventive Action (CAPA)
• Communication of Drug safety concerns to Consumer, HCPs, PvPI and the National Regulatory Authority
• Summary of Product Characteristics (SmPCs) and Prescribing Information Leaflets (PILs) with history of revisions

B. SOPs should include the following:

• Description of the process, data handling and records of PV performance
• ICSR collection, collation, follow-up, causality assessment and reporting;
• PSUR scheduling, preparation and submission
• Quality issue, recall or withdrawal of pharmaceutical products
• Training procedures, evaluations and documentations
• Signal detection and evaluation process
• Communication of safety concerns to consumers, HCPs and regulatory authorities
• Implementation of safety variations in PILs/SmPCs
• Safety data exchange agreements, if any
• Safety data archival and retrieval
• PV audit and inspections
• Quality control for PV activities
• Risk Management Plan
• Any other relevant SOP for establishing PV system at MAH organization

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C. Computerized systems and database

The location, functionality and operational responsibility for computerized systems and databases for receiving, collating and reporting safety information should be described in PSMF. Validation status of computer system functionality with change control, if any; nature of testing; back-up procedures should also be described. The MAH can have data collection in excel spreadsheets to record and track the data.

D. Quality Management System (QMS) in Pharmacovigilance

The QMS should be established in PV activities, which should include:

• Document and record control: The MAHs should retain the soft copy back-up of all PV documents for indefinite time and hard copies for at least 10 years. The MAHs shall maintain a logbook/excel spreadsheet/electronic data management tools for recording primary information received for every adverse event reported.
• Trainings: A summary of training records and files should be available at the PV site of MAH. Staff should be appropriately trained for performing PV-related activities, including any individual, who may receive products safety reports.
• Auditing: The Quality Assurance (QA) of the organization should supervise/facilitate the internal and external audits of PV system. The audit report must be documented within the quality system; with a brief description of the CAPA associated with the significant findings, the date it was identified and the anticipated resolution date(s) with cross reference to the audit report and the documented CAPA plan(s).

5. Pharmacovigilance System Performance

The key indicators for the performance of PV system e.g., number and quality of ICSRs, CAPA needs to be identified and measured for annual trend analysis.

The PSMF should contain evidence of the ongoing monitoring of the PV system performance including compliance of the main PV output. The PSMF should include a description of the monitoring methods applied and contain as a minimum the following:

• An explanation of how the correct reporting of ICSRs is assessed. In the annexure, figures/graphs should be provided to show the timelines of submission
• A description of any metrics used to monitor the quality of submissions and performance of PV. This should include information provided by the regulatory authority regarding the quality of ICSR reporting, PSURs or other submissions
• An overview of the timelines of PSUR reporting
• An overview of the methods used to ensure submission of safety variation to competent authority
• Wherever applicable, an overview of adherence to RMP commitments, or other obligations or conditions of marketing authorization(s) relevant to PV

Annexures to the PSMF

1. A list of pharmaceutical products including the name of the pharmaceutical product, active substance(s) and excipients
2. A list of contract agreements covering delegated activities including the pharmaceutical products
3. A list of tasks delegated by the PVOIC for PV
4. A list of all completed audits/inspection (regulatory as well as internal) and a list of audit/ inspection schedules

ALSO READ: Pharmacovigilance Audit Checklist