Biosimilar medicines: Overview

A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines. The European Medicines Agency (EMA) is responsible for evaluating the majority of applications to market biosimilars in the European Union (EU).

Biological medicines offer treatment options for patients with chronic and often disabling conditions such as diabetes, autoimmune disease and cancers.

Biological medicines contain active substances from a biological source, such as living cells or organisms (human, animals and microorganisms such as bacteria or yeast) and are often produced by cutting-edge technology.

Most biological medicines in current clinical use contain active substances made of proteins. These can differ in size and structural complexity, from simple proteins like insulin or growth hormone to more complex ones such as coagulation factors or monoclonal antibodies.

Image - Examples of types of proteins in biological medicines approved in the EU

Image - Examples of types of proteins in biological medicines approved in the EU: Text version

• Insulin - 5,808 daltons
• Growth hormone - 22,000 daltons
• Monoclonal antibody - 150,000 daltons

A biosimilar is a biological medicine highly similar to another biological medicine already approved in the EU (called 'reference medicine') in terms of structure, biological activity and efficacy, safety and immunogenicity profile (the intrinsic ability of proteins and other biological medicines to cause an immune response).

The EU approved the first biosimilar in 2006.

A biosimilar is not regarded as a generic of a biological medicine. This is mostly because the natural variability and more complex manufacturing of biological medicines do not allow an exact replication of the molecular micro-heterogeneity.

The EU has pioneered the regulation of biosimilar medicines by establishing a solid framework for their approval and by shaping biosimilar development globally.

The evidence acquired over ten years of clinical experience shows that biosimilars approved through EMA can be used as safely and effectively in all their approved indications as other biological medicines.

For the list of biosimilar medicines approved via the centralised procedure via EMA, see:

• Centrally authorised biosimilar medicines

Information for patients and healthcare professionals

EMA and the European Commission have developed information materials on biosimilar medicines to improve understanding of these medicines in the EU.

Video - What is a biosimilar? 

EMA's Chief Medical Officer, Steffen Thirstrup, explains what biosimilars are and how they work in the video below:

Video - Biosimilars (multi-language)

The animated video below presents key facts on biosimilar medicines and explains how EMA works to ensure that they are as safe and effective as their reference biological medicines:

The video is also available in the following European languages: Czech (subtitles), Dutch, English, Estonian (subtitles), French, German, Italian, Polish, Portuguese, Slovenian (subtitles) and Spanish. EMA plans to publish further language versions when available.

Related information material

An information guide for patients published by the European Commission explains in a clear, unbiased way: 

• what biosimilar medicines are;
• how they are developed and approved in the EU;
• what patients can expect in terms of availability and safety.

EMA and organisations representing patients contributed to the development of this guide.

It is available in 23 official EU languages on the Commission's website: 

• European Commission - What I need to know about biosimilar medicines: information for patients

EMA and the European Commission have also published a guide for healthcare professionals to provide reference information on the science and regulation underpinning the use of biosimilar medicines.

EU scientific experts and organisations representing doctors, nurses, pharmacists and patients contributed to the development of this guide.

It is available in 23 official EU languages:

Biosimilars in the EU - Information guide for healthcare professionals

Biosimilar development and approval in the EU

Reflection paper on biosimilar development and evaluation: public consultation

A draft reflection paper on a tailored clinical approach in biosimilar development and evaluation was available for public consultation.

This approach could reduce the amount of clinical data required to develop and approve biosimilar medicines.

For more information on this reflection paper, see:

• Reflection paper on a tailored clinical approach in biosimilar development

How EMA evaluates biosimilars

EMA's scientific committees evaluate the majority of marketing authorisation applications for biosimilar medicines before they can be approved and marketed in the EU.

EMA evaluates biosimilars according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines approved in the EU.

Developers of biosimilars are required to demonstrate through comprehensive comparability studies with the 'reference' biological medicine that:

• their biological medicine is highly similar to the reference medicine, notwithstanding natural variability inherent to all biological medicines;
• there are no clinically meaningful differences between the biosimilar and the reference medicine in terms of safety, quality and efficacy.

This allows avoiding the unnecessary repetition of clinical trials already carried out with the reference medicine.

Biosimilar competition should improve patient access to safe and effective biological medicines with proven quality.

Image - Comparison of data requirements for approval of a biosimilar versus the reference medicine

 

Image - Comparison of data requirements for approval of a biosimilar versus the reference medicine: Text version

Reference medicine	Biosimilar medicine
Risk management plan	Risk management plan
Clinical studies Safety and efficacy Pharmacokinetic (PK) /  Pharmacodynamic (PD) Immunogenicity	Comparative clinical studies Safety and efficacy Pharmacokinetic (PK) /  Pharmacodynamic (PD) Immunogenicity  Comparative non-clinical studies
Non-clinical studies	Comparative quality studies
Pharmaceutical quality studies	Pharmaceutical quality studies

Biosimilars can only be authorised once the period of data exclusivity on the 'reference' biological medicine has expired.

In general, this means that the biological reference medicine must have been authorised for at least eight years before another company can apply for approval of a similar biological medicine.

Interchangeability of biosimilar medicines in the EU

EMA and the Heads of Medicines Agencies (HMA) have emphasised that biosimilars approved in the EU are interchangeable from a scientific viewpoint, meaning that a biosimilar can be used instead of its reference product, or vice versa.

A biosimilar can likewise be used in place of another biosimilar of the same reference product.

Any interchange should only take place after careful consideration of the product information.

Statement on the scientific rationale supporting interchangeability of biosimilar medicines in the EU

Reference Number: EMA/627319/2022

Video - Interchangeability of biosimilar medicines in the EU

EMA's Chief Medical Officer, Steffen Thirstrup, summarises the interchangeability of biosimilars in the video below: 

EU Member States continue to decide which biological medicines are available for prescribing in their country and whether automatic substitution with biosimilars is allowed at pharmacy level. 

The EMA / HMA statement aims to address any uncertainty among prescribers of biological medicines and support patient access to biosimilars for treating diseases such as cancer, diabetes and rheumatic diseases. 

A 'questions and answers' document is available for healthcare professionals, patients and other stakeholders to further address issues related to the interchangeability of biosimilars in EU countries.

Q&A on the Statement on the scientific rationale supporting interchangeability of biosimilar medicines in the EU

Reference Number: EMA/93740/2023 Rev. 1

Infographic - Overview of biosimilars approved in the EU 

Infographic - Overview of biosimilars approved in the EU: Text version

Biosimilars in the EU

86 biosimilar medicines approved in the EU between 2006 and 2022. This includes approved biosimilars no longer on the EU market

Main therapeutic areas

• cancer
• diabetes
• rheumatoid arthritis

Safety data from 1 million patient-treatment years show that biosimilars are safe and can be used interchangeably

Patients and healthcare professionals with questions on practical aspects of biosimilar interchangeability should contact the national health authorities in their country:

• National competent authorities (human)

EMA can help address questions on how biosimilars are approved and monitored in the EU:

• Send a question to the European Medicines Agency

Regulatory guidance

EMA has published scientific guidelines to help developers of biosimilar medicines conform to the strict regulatory requirements for approving biosimilars and to provide transparency on the requirements for approving biosimilars.

Applicants preparing to request marketing authorisation for a biosimilar medicine via EMA should follow the Agency's procedural advice for the centralised authorisation of biosimilar medicines.

The safety of biosimilars is monitored through pharmacovigilance activities once they are on the market, in the same way as for other medicines.