METHODOLOGICAL MODEL FOR STRATIFICATION AND MANAGEMENT OF CRITICAL DRUG RISKS
DOI:
https://doi.org/10.11603/2312-0967.2026.1.15936Keywords:
pharmacovigilance, risk stratification, stratification model, risk management plan, important risks, risk minimization measuresAbstract
Introduction: The structural and chemical characteristics of active pharmaceutical ingredients determine the mechanism of action, efficacy, and safety profile of medicinal products. Risk identification and stratification are fundamental elements of the pharmacovigilance system, ensuring the safe use of medicines. Changes in Module V of the Good Vigilance Practice have increased the focus on clinical outcomes and targeted risk management, necessitating the development of new methodological tools for Marketing Authorization Holders. The authors of this publication have developed an algorithm which, based on testing results, proved suitable for identifying and stratifying important risks of drugs. Consequently, this tool can be proposed to applicants for use in the field of risk management.
Objective: To develop and validate a structured model for the identification and stratification of important risks of medicinal products and to provide a rationale for risk management approaches.
Materials and Methods: Bibliosemantic, analytical, expert assessment, and modeling methods were employed. The research objects included current GVP requirements and the safety profile of a randomly selected medicinal product containing L-arginini hydrochloridum (solution for infusion) (LAH) as the active substance.
Results: A comprehensive methodological model for risk stratification was developed based on the updated GVP Module V (Rev 2). Unlike previous algorithms, which often led to Risk Management Plans being overloaded with excessive amounts of insignificant data, the proposed model focuses on the clinical significance of each individual risk and the necessity for specific control measures. The model structurally consists of 8 thematic blocks covering 41 sequential evaluation criteria. The operational algorithm is based on a system of closed-ended questions ("Yes"/"No"), which minimizes expert subjectivity during decision-making. The evaluation process begins with the analysis of preclinical data and clinical trial results, followed by risk verification based on criteria of seriousness, frequency, and potential public health impact.
The key stage of the model is the direct stratification process, consisting of two phases: quantitative and qualitative. In the quantitative phase (screening), a risk is classified as "important" if it receives 25% or more "Yes" responses according to defined criteria. In the qualitative phase, the final list is formed through analysis involving final inclusion, reclassification, or exclusion of certain risks. This stage also ensures a clear differentiation of important risks into identified risks, potential risks, and missing information. Practical validation of the model was conducted using the safety profile of LAH.
Conclusions: The proposed structured model enables Marketing Authorization Holders to effectively distinguish between important risks (identified, potential, and missing information) and non-important risks. The algorithm ensures the conciseness and practical orientation of Risk Management Plans by excluding well-characterized risks that do not require additional minimization measures. This model serves as a universal tool for characterizing the safety profile of a medicinal product throughout its entire lifecycle.
References
Council for International Organizations of Medical Sciences. Benefit-risk balance for medicinal products: Report of CIOMS Working Group XII. Geneva: CIOMS; 2025. Available from: https://cioms.ch/publications/product/benefit-risk-balance-for-medicinal-products/ DOI: 10.56759/gwfz1791. DOI: https://doi.org/10.56759/gwfz1791
Esslinger S, Quinn L, Sampat S, Otero-Lobato M, Noël W, Geldhof A, et al. Risk Management Plans: reassessment of safety concerns based on Good Pharmacovigilance Practices Module V (Revision 2) – a company experience. J Pharm Health Care Sci. 2022 May 5;8(1):14. DOI: 10.1186/s40780-022-00244-z. DOI: https://doi.org/10.1186/s40780-022-00244-z
CIOMS and ICH Initiatives in Pharmacovigilance and Risk Management: Overview and Implications. Drug Saf. 2004;27(8):509-17. Available from: https://link.springer.com/article/10.2165/00002018-200427080-00004. DOI: https://doi.org/10.2165/00002018-200427080-00004
European Medicines Agency. Guidance on the format of the risk management plan (RMP) in the EU – in integrated format. EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2. Amsterdam: EMA; 2018 Oct 31.
Von Bruchhausen T, Schirp S. EMA releases the revised Good Pharmacovigilance Practices Module V: Updated guidance on risk management plans. Med Writ. 2017;26(3):48-51.
Akula A. EMA’s revised format for risk management plans – What you need to know. Pharm Online [Internet]. 2018 Sep 17 [cited 2024 May 22]. Available from: https://www.pharmaceuticalonline.com/doc/ema-s-revised-format-for-risk-management-plans-what-you-needto-know-0001
European Medicines Agency, Heads of Medicines Agencies. Guideline on good pharmacovigilance practices (GVP) Module V – Risk management systems. EMA/838713/2011. London: EMA; 2012 Feb 20.
European Medicines Agency, Heads of Medicines Agencies. Guideline on good pharmacovigilance practices (GVP) Module V – Risk management systems (Rev 1). EMA/838713/2011 Rev 1*. London: EMA; 2014 Apr 15.
European Medicines Agency, Heads of Medicines Agencies. Guideline on good pharmacovigilance practices (GVP) Module V – Risk management systems (Rev 2). EMA/838713/2011 Rev 2*. London/Amsterdam: EMA; 2017 Mar 28.
European Medicines Agency, Heads of Medicines Agencies. Guideline on good pharmacovigilance practices (GVP) Module VII – Periodic safety update report (Rev 1). EMA/816292/2011 Rev 1*. London: EMA; 2013 Dec 9.
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