DRAP Guidelines on National Pharmacovigilance System: Overview

Table of content

The Drug Regulatory Authority of Pakistan (DRAP), a country’s agency in the sphere of healthcare products, has published a new revision of the guidelines on the national pharmacovigilance system. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance. 

At the same time, the authority reserves the right to make changes to the document, should such changes be reasonably necessary to reflect corresponding amendments to the underlying legislation.

History of the Guidelines

This document represents the 3rd edition of the pharmacovigilance guidelines. Initially, the 1st edition was formulated in accordance with the draft Pharmacovigilance Rules and provided specific chapters and sections targeting healthcare professionals, patients, and registration holders. 

Subsequently, the National Pharmacovigilance Centre (NPC) issued the 2nd edition, titled “Guidelines on the National Pharmacovigilance System”, aligning it with the officially notified Pharmacovigilance Rules, 2022 under S.R.O 540 (I)/2022, dated April 22, 2022. In this edition, sections meant for stakeholder guidance were removed, and WHO Pharmacovigilance (PV) indicators were incorporated in Chapter 11. 

The current 3rd edition has been updated to integrate WHO recommendations from its assessment of the National Regulatory System under DRAP. These updates formalize the advisory role of PRAEC in signal management and risk assessment while mandating the NPC to handle signal management, risk assessment, and related decisions for risk minimization and regulatory actions in coordination with relevant DRAP Boards and Committees.

Application and Purpose

As explained by the authority, this document serves as a resource for all pharmacovigilance stakeholders in Pakistan, ensuring they understand and fulfill their roles in maintaining therapeutic safety.

The guidelines aim to provide a foundational framework to operationalize pharmacovigilance in Pakistan. Specific objectives include:

1. Operationalizing the National Pharmacovigilance Program.
2. Detecting, validating, and assessing new signals in the National Pharmacovigilance database.
3. Monitoring the benefit-risk ratio of therapeutic goods in the market.
4. Encouraging and guiding stakeholders to report pharmacovigilance data effectively.
5. Facilitating the identification and assessment of Adverse Events (AEs), Adverse Drug Reactions (ADRs), and Adverse Events Following Immunization (AEFIs) while supporting subsequent signal detection and risk communication.

Introduction

In accordance with the applicable regulatory requirements, therapeutic goods, including drugs, vaccines, and biologicals, undergo rigorous testing in clinical trials before their release. However, clinical trials have limitations in identifying all potential Adverse Drug Reactions (ADRs). 

As further explained by the authority, there are certain limitations of clinical trials to be taken into consideration, such as:

1. Limited population size: The number of trial subjects is smaller than the real-world patient base.
2. Selective participant criteria: Vulnerable groups such as pregnant women, elderly individuals, children, and those with comorbidities or on concomitant medications are often excluded.
3. Short duration: Clinical trials last only a few years, unlike prolonged real-world use.

Recognizing these limitations and inspired by the global response to the Thalidomide tragedy, robust post-marketing safety monitoring systems were established. The Drug Regulatory Authority of Pakistan responded by creating the National Pharmacovigilance Centre (NPC) under its Division of Pharmacy Services. 

The role and achievements of NPC include:

• The NPC actively coordinates at national and international levels to develop pharmacovigilance in Pakistan.
• It facilitated Pakistan’s membership as the 134th full member of the WHO Programme for International Drug Monitoring (WHO-PIDM) in 2018.
• NPC has developed various reporting tools and guidelines, now accessible via its official website.

With the introduction of the Pharmacovigilance Rules, 2022, it is now mandatory for stakeholders to establish their pharmacovigilance systems and report data to NPC.

Terms and Definitions

In order to assist the parties involved with interpreting the relevant provisions of the applicable regulations, the guidelines provide clarity on key pharmacovigilance terms. Below are some important definitions:

1. Adverse Drug Reaction (ADR): A noxious and unintended response to a drug occurring at normal doses, where a causal link between the drug and the reaction is reasonably suspected.
2. Adverse Event (AE): Any untoward medical occurrence during treatment, not necessarily linked causally to the therapeutic good.
3. Adverse Event Following Immunizations (AEFI): Any medical occurrence post-immunization, independent of a causal relationship with the vaccine.
4. Signal: Reported information on a possible causal relationship between a therapeutic good and an adverse event, often requiring further review or action.
5. Benefit-Risk Assessment: Continuous evaluation of the pros and cons of a treatment to ensure the benefits outweigh the risks.

Key Stakeholders and Roles

The document further names the key parties involved and also outlines their responsibilities. 

Pharmacovigilance Entities

1. NPC (National Pharmacovigilance Centre): Established under Rule 3 of the Pharmacovigilance Rules, 2022, the NPC oversees national pharmacovigilance activities.
2. PRAEC (Pharmacovigilance Risk Assessment Expert Committee): Advises on risk management, signal detection, and causality assessment.
3. PPC (Provincial Pharmacovigilance Centres): Provincial counterparts responsible for implementing pharmacovigilance under Rule 5.

Healthcare Professionals (HCPs)

HCPs, including doctors, pharmacists, nurses, and allied health workers, play a vitally important role in:

• Reporting ADRs, AEs, and AEFIs.
• Ensuring proper use of therapeutic goods to minimize risks.

Surveillance and Reporting Systems

According to the document, pharmacovigilance relies on active and passive surveillance methods:

1. Passive Surveillance: Involves spontaneous reporting by HCPs or patients of ADRs and AEs to registration holders or regulatory authorities.
2. Active Surveillance: Targets enhanced monitoring of specific therapeutic goods or events to ensure complete data collection on adverse outcomes.

Additionally, the Individual Case Safety Report (ICSR) framework standardizes the reporting of suspected ADRs linked to medicinal products or therapeutic goods.

Safety Monitoring and Risk Minimization

To ensure ongoing safety, pharmacovigilance involves:

• Signal detection: Identifying new safety concerns from reported data.
• Causality assessment: Determining the likelihood of a causal link between a therapeutic good and an adverse reaction.
• Risk communication: Alerting relevant stakeholders to potential safety risks.

Regulatory Obligations

Under the Pharmacovigilance Rules, 2022, all stakeholders, including registration holders and public health programs (PHPs), are legally required to:

1. Establish pharmacovigilance systems.
2. Report pharmacovigilance data to the NPC.
3. Participate in safety and efficacy studies when required.

Conclusion

In summary, these guidelines are intended to enhance Pakistan’s pharmacovigilance framework, ensuring that therapeutic goods are monitored for safety in real-world settings. The document seeks to uphold public health through effective risk management and safety assurance by addressing gaps in clinical trials and promoting active stakeholder participation.

Source

https://www.dra.gov.pk/wp-content/uploads/2024/10/NPVG-guidelines-reviewed-final-10-10-24.pdf

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