On 22 August 2025, the EMA issued Good Pharmacovigilance Practices (GVP) Module XVI Addendum I – Risk minimisation measures for medicinal products with embryo-foetal risks (EMA/608947/2021).
This Addendum to Module XVI provides essential guidance on when and how to implement risk minimisation measures (RMMs) for products with embryo-foetal risks while ensuring patient medical needs are not compromised when no suitable alternative treatments are available.
The Addendum offers some clarity as to what constitutes a Pregnancy Prevention Programme (PPP). Historically, without clear guidance, there has been a tendency to equate a PPP with a Controlled Access Programme such that specific activities, e.g. pregnancy testing must be performed, documented and verified prior to dispensing the medicinal product. This has proved challenging in several European Member States where either local regulations, healthcare organization, or culture have created obstacles to such implementation.
GVP Module XVI Revision 31 introduced concept of Control Tools and listed a number of different activities for consideration. These included one or more of the following:
- Healthcare professional qualification
- Healthcare facility accreditation
- A traceability system
- A system for documenting exchange of information
- Certificates of medical interventions which are required for the prescribing or dispensing of the medicinal product
Addendum I, released in August 2025,2 describes intended actions for risk minimisation applied to embryo-foetal risks (e.g., counselling, taking actions to avoid pregnancy, pregnancy testing, supervision of treatment and avoiding blood or sperm donation if applicable) and the tools that can be used as RMMs applied to embryo-foetal risks. These tools include routine RMMs such as:
- Product labelling
- Visual enhancements, special warnings on packaging
- Disallowing free samples
Additional RMMs include:
- Educational materials for healthcare professionals
- Educational materials for patients
Addendum I further states in exceptional situations of embryo-foetal risks of a medicinal product, intended actions for risk minimisation and RMM tools can be combined to form a PPP. It states that a PPP is constituted by at least the following:
- Contraindication or a contraindication unless there is no suitable alternative treatment during pregnancy
- Risk counselling
- Taking actions to avoid pregnancy
- Pregnancy testing
- Supervision of treatment
- Reminder statements of risk of embryo-foetal risk on outer packaging
- Educational material for healthcare professionals
- Educational material for patients
The Addendum goes on to say that the PPP may include one or more of the control tools listed above but not to the extent that a control tool is a mandatory part of a PPP.
UBC welcomes this guidance which provides clarity on what constitutes a PPP and believes it is key to ensuring patient access to medicines across all Member States in the EU while maintaining patient safety.
This clarification related to EU risk minimization measures comes at a time where risk management shifts have also been seen in the United States. In July 2025, FDA announced that risk evaluation and mitigation strategy (REMS) requirements for embryofetal toxicity risks would be removed from all endothelin receptor antagonist medicines.3 The REMS requirements had previously been based on findings from animal studies and FDA monitoring of data over time did not show a pattern of congenital malformations consistent with what was observed in animal embryofetal toxicity studies.
This evolution in risk management, grounded in evidenced-based decision making, is a promising step to ensure patients have access to life-changing medicines in an ever-changing healthcare landscape.
References
1. European Medicines Agency. Guideline on good pharmacovigilance practices (GVP). Module XVI – Risk minimisation measures (Rev 3). July 26, 2024. Accessed September 16, 2025. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-good-pharmacovigilance-practices-gvp-module-xvi-risk-minimisation-measures-rev-3_en.pdf
2. European Medicines Agency. Guideline on good pharmacovigilance practices (GVP). Module XVI Addendum I – Risk minimisation measures for medicinal products with embryo-fetal risks. August 22, 2025. Accessed September 16, 2025. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-gvp-module-xvi-addendum-i-risk-minimisation-measures-medicinal-products-embryo-fetal-risks_en.pdf
3. U.S. Food & Drug Administration. Endothelin Receptor Antagonist REMS Information. July 3, 2025. Accessed September 16, 2025. https://www.fda.gov/drugs/information-drug-class/endothelin-receptor-antagonist-rems-information
About UBC
United BioSource LLC (UBC) is the leading provider of evidence development solutions with expertise in uniting evidence and access. UBC helps biopharma mitigate risk, address product hurdles, and demonstrate safety, efficacy, and value under real-world conditions. UBC leads the market in providing integrated, comprehensive clinical, safety, and commercialization services and is uniquely positioned to seamlessly integrate best-in-class services throughout the lifecycle of a product.
UBC is a leader in risk management and REMS activities and can help Sponsors develop, implement, and assess risk management strategies. Our consultation, design, implementation, and evaluation offer a cohesive experience throughout a product’s life cycle. Our subject matter experts (SMEs) remain on the cutting edge of developments across all facets of risk management and can support customers in securing safe and appropriate use of their products.
About the Author
Dr. Janine Collins, MBBS, LLM. Vice President, Medical, Scientific & Real-World Research
Dr. Janine Collins, MBBS, LLM, is Vice President, Medical, Scientific & Real-World Research at UBC. She provides leadership, direction, and guidance supporting customers in the creation of core Risk Management Plans and global and local strategy for Risk Management activities. Her experience spans a wealth of therapeutic areas and latterly has focused on several rare diseases in both adults and pediatrics including metabolic disorders, inborn errors of metabolism, neurodegenerative disorders, and pediatric and adult oncology.
