The International Conference on Harmonization of Technical Requirements for the registration of pharmaceuticals for human use, or the ICH, was formed to facilitate harmonization of requirements and procedures among member states to ensure safe, efficacious, and high-quality drugs reach the market. The founding regulatory members include the European Commission (EC) of Europe, the Food and Drug Administration (FDA) of the USA, and the Ministry of Health, Labour, and Welfare (MHLW)/Pharmaceuticals and Medical Device Agency (PMDA) of Japan. The ICH E2A- E2F guidelines provide a standard approach to pharmacovigilance (PV) and post-market safety surveillance, however, certain PV approaches differ among these members.
The European Medicines Agency (EMA) established the GVP guidelines that are applicable to EU Member States and the European Economic Area (EEA) for pharmaceutical products that are approved in these regions. These modules within the guidelines are divided into 2 categories- modules that cover main PV processes (I to XVI) and product or population-specific considerations. A Qualified Person for Pharmacovigilance (QPPV) is mandated by the EMA who is responsible for all PV activities as well as maintaining PV systems within EU and/or EEA. Member States may appoint a national QPPV personnel. The EMA requires PSUR or PBRER aggregate reports for pharmaceutical products, though PBRERs are preferred as they are more comprehensive.
Post Brexit changes
Many changes in UK legislations were made during the post-transition phase of Brexit- one of the biggest geopolitical moves in recent years. The UK PV legislation was implemented on the 1st January 2021 that were based on GVP guidelines, however, demonstrated minor changes for ICSR submissions, the need for a UK QPPV, RMPS and PSURs.
United States of America
The US FDA does not mandate a QPPV or Pharmacovigilance System Master File (PSMF). However, if required, the marketing authorization holder (MAH) must be able to demonstrate that a robust PV system is in place. Instead of a risk minimization plan (RMP), the US FDA requires a risk evaluation and mitigation strategy (REMS) document. While the aim of the RMP and REMS is the same- to identify, characterize, and prevent or minimize risks associated with a product- both documents exhibit certain different approaches. While the EMA requires an RMP for all medicinal products, the US FDA requires REMS for certain products. It also provides risk minimization measures for specific identified risks during the product lifecycle, and consists of medication guides, communication plans, and elements to assure safe use (ETASU).
The PMDA implemented the Medical Information for Risk Assessment Initiative (MIHARI) project that developed scientific research and analyses databases of electronic medical records to evaluated submitted reports of adverse drug reactions (ADRs). An advantage of MIHARI is that only the target population is analyzed where comparative & quantitative assessment can be conducted. Furthermore, the PMDA has its own RMP format that includes safety specifications, PV activities, and risk minimization measures for a pharmaceutical product. The PMDA mandates PSURs that must be submitted to the MHLW every 6 months for 2 years and annually thereafter during their ‘re-examination’ period. After the period is over, PSURs must be submitted every 5 years.
Pharmacovigilance Services with DDReg
DDReg is reputed for its end-to-end pharmacovigilance services across the globe, including the USA, EU, and Japan, that includes ICSR Processing & Submission, RMP & REMS support, Aggregate Report, Signal Management, QPPV Services, PV Audit & Compliance and more. The safety team has supported multiple organizations worldwide in setting up PV systems that are compliant with relevant regulations and standards.
References and Further Reading
- European Medicines Agency. Good Pharmacovigilance Practice 2022
- Medicines and Health Products Regulatory Agency. Guidance on Pharmacovigilance Procedures. 2022
- United States Food and Drug Administration. Good Pharmacovigilance Practices & Pharmacoepidemiologic Assessment. 2005
- Pharmaceuticals and Medical Devices Agency, Japan. Post-marketing safety measures. 2022
- Pharmaceuticals and Medical Devices Agency, Japan. MIHARI project. 2009