Development of a checklist for the assessment of pharmacovigilance guidelines in Southern Africa: a document review

Abstract

Introduction: National regulatory systems in Southern Africa reflect various stages of maturity, and pharmacovigilance (PV) practices are not aligned. In the absence of guidance for formulating PV guidelines in Southern African Development Community (SADC) countries, this study aimed to create a checklist that may be used to assess the rigour of PV guidelines in this region and provide guidance for the National Medicines Regulatory Agency (NMRA) authors. Methods: A document analysis was performed based on harmonised international guidelines ( n = 22) that prescribed methods of PV regulation to identify themes and items to incorporate into a checklist. The contextualisation of the checklist to the African pharmaceutical environment was accomplished by referencing peer-reviewed journal articles ( n = 7). The checklist was subjected to face and content validation by non-experts and PV experts. Results: The document review yielded 5 themes, 18 sub-themes, and 73 items structured into the checklist. Themes encompassed PV systems, definitions, individual case safety reporting, aggregate reporting, and risk management. Under PV systems, aspects of the quality management system were outlined, that is, the legal basis for PV, a description of the marketing authorisation holder’s (MAH’s) PV system, archiving of data, contracting of PV tasks, and the duties of the person responsible for the MAH’s PV obligations. Definitions of the key terms and major stakeholders were identified. Reporting of individual case safety reports (ICSRs) was explicated by considering the criteria for reporting, categories of reportable information, expedited reporting requirements, reporting timelines, and ICSR reporting format. Aggregate report submission during the development and post-marketing phases was addressed. Risk management encompassed signal detection, re-evaluation of the benefit-risk ratio, the safety decision-making process, risk management planning, risk minimisation and safety communication. Conclusion: The developed checklist can contribute towards assisting SADC NMRAs to formulate national PV guidelines that reflect current international practice, with local context incorporated. Plain Language Summary Developing a checklist for the evaluation of medicine safety guidelines in Southern Africa Introduction: In Southern African Development Community (SADC) countries, the guidelines for medicine safety [pharmacovigilance (PV)] that marketing authorisation holders (MAHs) and healthcare professionals need to adhere to, are not aligned. We saw the need to develop a checklist that can be used to evaluate these guidelines. Methods: We studied international documents issued by the World Health Organization (WHO), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the Council for International Organizations of Medical Sciences (CIOMS) and the European Medicines Agency (EMA). On the organisational websites, we obtained 22 documents and identified 73 checklist items. All the items were arranged under 5 themes and 18 sub-themes to create the checklist. We adapted the checklist to the local context by using seven journal articles addressing PV concerns in Africa. Experts checked the content and usability of the checklist. Results: The themes were PV systems, definitions, individual case safety reporting (ICSR), combined reporting and risk management. PV systems had six sub-themes: legal structure, description of the MAH’s PV system, contractual agreements, information storage, the qualified person responsible for PV (QPPV) and where the QPPV is located. We included the definitions of keywords and role-players. The ICSR theme had five sub-themes, i.e. criteria for reporting, categories of reportable information, expedited reporting, reporting timelines, and reporting format. Submission of summary reports comprised an overview of the safety profile of a medicine once it is approved by regulators, as well as during clinical trials. Risk management included signal detection, re-evaluation of the benefit-risk ratio, safety decision-making process, risk management planning, risk minimisation, and safety communication. The checklist is applied by allocating yes/no scoring per item. Conclusion: The checklist may be used by regulators within SADC to assess their PV guidelines for alignment with international standards and suitability to the local environment.