Action Point 15 - Strategy to strengthen the capacity to assess and manage risks associated with medical products

Last update: 04/07/2024

Background

The WHO has defined pharmacovigilance as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problems. Prevention of adverse effects, that is taking action to minimize the identified risk, is essential to safeguard public health.

Multiple actors can be involved in the management of the risks associated with medical products. Governments, ministries of health, National Regulatory Authorities, pharmacovigilance centers, public health programmes, and Health care professionals, among others, play a critical role in informing and educating their public, and in influencing behaviours towards the adequate use of medical products.

In the scope of individual products, and while there is no globally accepted definition of a risk management plan (RMP), it is generally a document included in the marketing authorisation which describes the planning of pharmacovigilance activities, based on the safety specifications, including the pharmacovigilance plan and the risk minimisation measures (ICH E2E).

While RMPs are critical in planning pharmacovigilance activities and ensuring that risk minimisation measures relevant to the local context are adequate, there is limited experience in SEARN of the assessment of such documents. While there is a need to build capacity in the region in assessing RMPs, there may also be opportunities for reliance and worksharing.

Considering these challenges, the Assembly created in 2023 a dedicated action point (AP15) in the SEARN workplan, led by Working Group 3 (WG3) Vigilance.

Main objective

To develop a strategy to strengthen the capacity to assess and manage risks associated with medical products at the regional level.

Definitions and scope

The scope of this strategy was limited to medicines and vaccines. The Council for International Organisations of Medical Sciences (CIOMS) Cumulative Glossary with focus on Pharmacovigilance was generally used as a reference for definitions.

Risk management

Requirements for effectively managing risks

Effectively managing risks requires the implementation of a system supported by adequate legal provisions, a quality management system (including guidelines, SOPs and templates), sufficient competent staff, and adequate engagement with the many stakeholders. Further guidance can be found from WHO and partners, starting with the Global Benchmarking Tool.

Specificities of the region regarding risk management

Compared to other parts of the world where pharmacovigilance has been more established, there are key specificities in SEARN countries which need to be carefully considered when addressing risks associated with medical products:

  • There is a diversity of regulatory systems and important differences in health systems compared to other parts of the world
  • There is a unique diversity of languages and diverse levels of literacy which can be a challenge for risk communication
  • Cultural aspects specific to South-East Asia may also have an influence on the effectiveness of risk minimization measures and should be considered in the assessment process
  • The capacities of local MAHs may be very limited in some settings compared to high-income countries

Risk management by health authorities

Beyond the obligations of marketing authorization holders, health authorities can play a key role in managing the risks of medical products, including through disease programmes.

This may include among other activities providing key information to prescribers and patients (e.g. through publishing SmPCs), integrating important safety information and recommendations from pharmacovigilance in the clinical recommendations and risk communication to the relevant healthcare professionals.

Health authorities may also conduct studies to assess and monitor a risk and/or the impact of risk minimization measures.

Risk management through marketing authorizations

In some countries, risks associated with medical products may be addressed in a marketing authorization through a risk management plan, which is part of the marketing authorization dossier.

 

Bangladesh

In Bangladesh, Good Pharmacovigilance practices (GVP) guidelines for MAH were published in 2023. An RMP should be submitted during registration for:

  1. A new medicine (molecule) that is introduced for the first time in Bangladesh. This molecule will be considered to be "new" for a period of four years from the date of first approval. Any MAH for this new medicine (molecule) should submit RMP.
  2. During registration for biologics and vaccines irrespective of new or old molecule

Post-registration, such submission is also required in the following situations:

  1. When there is a significant change to the benefit-risk balance of one or more medicinal products included in the RMP;
  2. When there is an application involving a significant change to an existing registered product, such as:
  • New or significant change in indication;
  • New dosage form;
  • New route of administration;
  • New manufacturing process of a biotechnologically-derived product;
  • New chemical form;
  • New dosage strength.

III. When there is a change in the list of the safety concerns or any changes in the existing additional pharmacovigilance or additional risk minimization activities;

  1. At the request of the Health Authority when there is a concern on a risk affecting the benefit-risk balance.

 

India

In India, the Indian Pharmacopoeia Commission, national coordination centre of the pharmacovigilance programme of India, has issued in 2018 a guidance document on pharmacovigilance for marketing authorization holders of pharmaceutical products. Further, CDSCO has issued Guidance for Industry on Pharmacovigilance requirements for human vaccines, updated in 2024.

 

Indonesia

In Indonesia, pharmaceutical industries must develop a Risk Management Plan (RMP) document since product development until the product is marketed. In Indonesia, RMPs are required for:

  1. New drug
  2. Biological product including biosimilar
  3. Certain generic drug
  4. Drugs with a change that may increase safety risks

The RMP document is part of the registration dossier and submitted to the Directorate of Drug Registration. RMP documents can be prepared using Indonesian or English language. The RMP format refers to the template in the guidelines or using the format in the country of origin (for imported products).

Pharmaceutical industries must report the implementation of RMP to The Indonesian FDA.

The RMP implementation report submitted to Indonesian National Pharmacovigilance Center (The Indonesian FDA c.q. Directorate of Safety, Quality and Export Import Control of Drug, Narcotic, Psychotropic, Precursor and Addictive Substance).

 

In other regions

Beyond SEARN, many guidelines are available on risk management plans, including:

Current practices among SEARN members

A survey was conducted to document and analyse current risk management practices in the region. The survey explored 3 main areas:

  • measures imposed to MAHs (legal provisions, guidelines, experience, examples and challenges),
  • capacities from health authorities (capacity, experience, examples and challenges),
  • awareness of health data base or other elements which could be used to conduct pharmacovigilance epidemiological studies in the region.

Highlights

  • The survey highlighted that the majority of SEARN members have legal provisions and experience to impose routine risk minimization measures to Marketing Authorization Holders (product information)
  • However, only few Members have legal provisions and/or experience on more advanced pharmacovigilance imposed activities, such as risk management plans or communication to healthcare professionals
  • Beyond, health authorities generally have capacities and experience on risk communication, risk minimisation, or engagement with stakeholders.
  • However, there are challenges regarding publishing product information and conducting studies.
  • One public healthcare database and some registries which may be used for Real World Evidence (RWE) -based pharmacoepidemiological studies were also identified during this survey.

Recommendations from WG3 on safety issues

A regional mechanism will be developed to enable WG3 to provide recommendations to its Members. The expertise in WG3 will be complemented by external experts, as well as a database for ad hoc expertise needs.

SEARN Members and the secretariat may submit to WG3 Vigilance safety issues for recommendations on the risk assessment and/or risk minimization measures. The scope may be any safety issue, related to vigilance and/or market control and surveillance activities. The expertise may be further strengthened by inviting experts and reference regulatory authorities beyond the region.

A template was developed to provide the required information, and it should be complemented by any relevant information (e.g. assessment report, publications, etc.).

SEARN Members should send this template and additional information to the secretariat, who will circulate it to WG3.

Any safety issue requiring advice from WG3 should be circulated at least 15 days before the meeting, and ideally at least one month before to allow the members to review the documentation.

The recommendations from SEARN WG3 will be published on the public website of SEARN.

Next steps

  1. Deepen the analysis of the survey on risk management and propose recommendations to SEARN, including engagement with stakeholders and capacity building
  2. Support the finalisation and implementation of the regional mechanism for risk assessment (including reliance) and the expansion of the composition of WG3 to support risk assessment (including the dedicated terms of reference, the nomination of additional experts, and the creation of an experts database)
  3. Pilot the regional mechanism for risk assessment with valproate