New EMA biosimilar guidelines for healthcare professionals


Healthcare professionals in the EU and US still have a cautious approach towards using biosimilars in clinical practice because of concerns over their safety and efficacy. This caution has led to limited use of biosimilars in patients requiring biological drugs as part of their treatment.1 The European Medicines Agency (EMA) has developed an “Information Guide for Healthcare Professionals”. The objective is to provide reference information on both science and regulation supporting the use of biosimilars. This guide has been prepared by the EMA in collaboration with the European Commission and scientific experts from EU Member States.2

Information Guide Overview

In 2006, the EU approved its first biosimilar, and clinical evidence collected to date demonstrates that biosimilars approved in the EU can be safely and effectively used in patients. The information guide consists of several chapters to summarise in detail the definition and features of biosimilars, clinical development process, regulatory framework of biosimilars in the EU, safety monitoring, data collection on biosimilarity, prescribing information, interchangeability, and the contribution of the EU to the regulation of biosimilars worldwide. Biological drugs contain active substances that are made up of proteins which are naturally variable. The EU has therefore implemented strict controls to ensure that this variability does not impact the safety and efficacy of these biosimilars. Biosimilars have the potential to cause immune responses, hence why the evaluation of their immunogenicity form such an integral part of the clinical development process.2

When a marketing approval is sought by a company, data are evaluated by the EMA’s scientific committees on human medicines and safety, by the EU “Biologics Working Party”, and “Biosimilar Working Party”. The final EU-wide marketing authorisation is granted by the European Commission following a review by the EMA. The EMA has developed several scientific guidelines, including product-specific guidelines, to help companies comply with strict regulatory requirements.2

Biosimilar Development and Approval in EU

The companies developing biosimilar drugs must prove pharmaceutical quality in terms of structural characterisation, physicochemical properties, purity such that the level of residues do not exceed acceptable levels, biological activity, excipients, strength, formulation, consistency in the manufacturing process, and stability of active substance. Robust non-clinical and clinical data needs to be collected from comparative studies to rule out the differences which may affect the safety and efficacy of the drug. The safety and efficacy data of the reference drug will be utilised by those developing biosimilars once the biosimilarity is established. This stepwise procedure is as follows:2

Step 1: Comparative quality studies

Analytical: Physical + Chemical Process
Functional: Biological / Pharmacological Activity

Step 2: Comparative non-clinical studies


Step 3: Comparative clinical studies

Pharmacokinetic / Pharacodynamic
Efficacy + Safety + Immunogenicity

Immunogenicity studies must be performed for the approval of biosimilars. If the biosimilar is highly similar to the reference drug in terms of safety and efficacy data for one therapeutic indication, this can then be used to extrapolate other indications of the reference drug. The robustness of data collected from these comparative quality, non-clinical and clinical studies will support the extrapolation.2


The EU has well-established systems for monitoring, reporting, assessing, and preventing adverse drug reactions of biologicals. Companies applying for marketing authorisation must submit risk management plans (RMPs) for each biosimilar, describing how safety will be monitored and the procedures for minimising risk. The EU may impose post-marketing studies on companies producing biosimilars to further assess their risks and monitor rare drug reactions, and periodic safety update reports may have to be submitted by marketing authorisation holders to evaluate ongoing safety. If the biosimilar is under additional monitoring, then a black triangle is displayed in the summary of product characteristics and package leaflet. For traceability, it is important that healthcare professionals record the trade and batch numbers of the biosimilars and mention the trade name in the prescription.2


It is expected that companies would introduce biosimilars at a lower price than their reference drugs. This biosimilar competition would improve patients’ access to biological drugs, especially for oncological and immunological indications. This improved access would offer a distinct advantage to healthcare systems in the EU.2


1Leonard E et al. Factors Affecting Health Care Provider Knowledge and Acceptance of Biosimilar Medicines: A Systematic Review. Manag Care Spec Pharm. 2019;25(1):102-12
2Biosimilars in the EU: Information Guide for Healthcare Professionals. Prepared jointly by the European Medicines Agency and the European Commission