A robust regulatory framework in the EU to protect patient safety (Directive 2001/83/EC, Regulation (EC) No 726/2004 and relevant regulatory guidelines) ensures that the safety and efficacy of biosimilars are closely monitored even after marketing in the EU.
As with all medicinal products for human use, the Marketing Authorization Holder should submit a Risk Management Plan (RMP) when applying for marketing authorization in the EU, which should account the specificity of these medicinal products (potential immunogenicity, variability etc.). After marketing approval, in addition to regular reporting of adverse reactions, safety data should be provided in pre-determined periods to EMA and national authorities in the form of regular update safety reports (PSURs). These reports shall include the updated safety information and an assessment of suspected adverse reactions, including adverse events of special interest (AESIs) as well as an evaluation of the impact of new data on the positive benefit-risk ratio. In general, after marketing authorisation approval, a post-marketing authorisation PSUR is submitted every 6 months for the first two years. The assessment of safety data and identified new safety signals are being evaluated at the EMA Pharmacovigilance Risk Assessment Committee (PRAC), where all EU Member States are involved. The PRAC evaluates if any change in the prescribed product information is necessary or whether any other pharmacovigilance measure should be implemented (as a last resort, if it is confirmed that the risks outweigh the benefits, this could result in withdrawal of the marketing authorisation). The safety data are collected in the European database called EudraVigilance- This database is available for the detection of any new safety signals, which is one of the regular pharmacovigilance activities for all medicinal products, and is carried out by the regulatory authorities, including EMA, and marketing authorisation holders. Information on suspected adverse drug reactions for all authorised medicinal products in the EU, including biologic and biosimilar medicinal products, is available in the form of summary reports in the European adrreports.eu database at the following link.
For biological and similar biological medicinal products with marketing authorisation obtained after 1st January 2011, the additional safety monitoring is required, as illustrated by the black triangle indicated in the SmPC and Package Leaflet (but not on the outer or immediate packaging!) The black symbol encourages healthcare professionals and patients to report directly on any suspected adverse drug reaction. It should be emphasized, that symbol does not mean that there are additional concerns about medicinal product safety. It is expected to report all suspected adverse reactions, even if the effect is already listed in the SmPC. This would enable more frequent detection of safety signals, assessment of identified risks and implementation of measures for the safe use of medicinal products. In order to clarify any new safety concerns or to obtain additional information on adverse reactions, post-authorisation safety study (PASS studies) may be required.
For pharmacovigilance of biological medicinal products, it is crucial to ensure the traceability of a particular medicinal product. In everyday clinical practice this is achieved by recording in the patient’s medical records the brand name and serial numbers of the medicinal product. It is also important to list this information in the report when adverse reaction is reported. At JAZMP, it is noted that the reporting of adverse reactions of biological or biosimilar medicinal product with its brand name and serial number is consistent in most reports. It is also noted that the number of reports on adverse events for biosimilars is similar to the number of reports on adverse events for original biologicals.
Biosimilars have been on the EU market for more than 15 years and it is important to notice that during this time no new adverse effects not already known for the reference product have been detected for the biosimilars. This strongly supports the presumption that once a biosimilar gets approval in EU, they indeed are clinically equivalent to the reference product.