21 April 2023
EMA/627319/2022

Statement on the scientific rationale supportinginterchangeability of biosimilar medicines in the EU
The EU experts on biosimilar medicines (Biosimilar Medicines Working Party or BMWP) and theHeads of Medicines’ Agencies (HMA) Biosimilar Working Group have drafted a joint statement
explaining the rationale for considering biosimilars approved in the EU as interchangeable from ascientific perspective. This statement has been endorsed by the Committee for Medicinal Productsfor Human Use (CHMP) and the Biologics Working Party (BWP).

Joint EMA-HMA statement on interchangeability:
Biosimilars approved in the EU are interchangeable
Interchangeability refers to the possibility of exchanging one medicine for another medicine that is
expected to have the same clinical effect.
HMA and EMA consider that once a biosimilar is approved in the EU it is interchangeable, whichmeans the biosimilar can be used instead of its reference product (or vice versa) or one
biosimilar can be replaced with another biosimilar of the same reference product. Interchange
should only take place after careful consideration of the approved conditions of use (i.e.,consulting the most recent product information).
Decisions on how to implement interchangeability either through switching (under the control ofthe prescriber) and/or substitution (the practice of dispensing one medicine instead of anothermedicine without consulting the prescriber, such as automatic substitution at the pharmacylevel), are not within the remit of EMA and are managed by individual member states.

Background
Interchangeability in the context of this statement means using one medicine instead of anotherwith the same therapeutic intent. How this is implemented is the responsibility of the individual
member states.
Biosimilars approved via EMA can be used interchangeably if national rules allow it. From ascientific viewpoint, interchangeability of approved biosimilars has always been considered
acceptable and did not raise any concern (1). However, EMA has to date not issued any
recommendation on interchangeability.
At present the EU medicines regulatory network has identified the need to explicitly state that froma scientific point of view, biosimilars approved in the EU can be considered interchangeable.
This is because the absence of a clear EU-wide position on interchangeability has been identified as
Official address

Domenico Scarlattilaan 6●1083 HS Amsterdam●The Netherlands

Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us
Send us a question Go to www.ema.europa.eu/contact

Telephone +31 (0)88 781 6000

An agency of the European Union© European Medicines Agency, 2023. Reproduction is authorised provided the source is acknowledged.

a factor causing uncertainty among stakeholders on the use of biosimilars in clinical practice (2).
Thus, EMA and HMA consider that a harmonised and clear EU wide position on interchangeability isneeded to reduce any uncertainty that prescribers may have when deciding to prescribe biologicalmedicines.

Scientific rationale
The EU regulatory network has been assessing, authorising and monitoring biosimilars for over 15
years and has gained very profound understanding of biosimilars after reviewing more than one
hundred biosimilar candidate submissions, and monitoring their safety once they are placed onto themarket.
Switching between biological medicinal products manufactured and commercialised by different
companies has become common in clinical practice, and interchangeability of EU-licensed biosimilars
has been confirmed (1, 2, 3, 4).
Approved biosimilars have demonstrated comparable efficacy, safety and immunogenicity comparedwith their reference products (5). Thus, EU experts consider that when approval for a biosimilar isgranted in the EU, additional systematic switch studies are not required to support theinterchangeability.
Considering all the available scientific evidence and the successful experience with biosimilars inclinical practice over the years, the CHMP and all working parties with expertise in biological
medicines and biosimilars support that medicines approved as biosimilars in the EU may beprescribed interchangeably. This will allow more patients to have access to biological medicines
necessary for treating diseases such as cancer, diabetes and rheumatic diseases.
Member States will continue to decide which biological medicines are available for prescribing ineach territory and whether automatic substitution is allowed at pharmacy level.
Information sources on biosimilars
Patients and healthcare professionals with specific questions on interchangeability practices arerecommended to contact the medicines regulatory agency in their member state: National competentauthorities (human) | European Medicines Agency (europa.eu).
For questions on how biosimilars are approved and monitored in the EU, patients and healthcare
professionals can contact EMA: Send a question to the European Medicines Agency | EuropeanMedicines Agency (europa.eu).

Statement on the scientific rationale supporting interchangeability of biosimilar
medicines in the EU
EMA/627319/2022

Page 2/3

References:
1. Interchangeability of Biosimilars: A European Perspective. Pekka Kurki, Leon van Aerts,
Elena Wolff-Holz, Thijs Giezen, Venke Skibeli, Martina Weise. BioDrugs 2017 Apr;31(2):8391
2. Regulatory Information and Guidance on Biosimilars and Their Use Across Europe: A Callfor Strengthened One Voice messaging. Liese Barbier, Allary Mbuaki, Steven Simoens,Paul Declerck, Arnold G. Vulto, and Isabelle Huys. Frontiers in Medicine 2022, Vol 9,820755
3. Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies andFusion Proteins: A Regulatory Perspective. Pekka Kurki, Sean Barry, Ingrid Bourges,Panagiota Tsantili, Elena Wolff-Holz. Drugs 2021 Nov;81(16):1881-1896
4. The safety of switching between therapeutic proteins. Ebbers H, Muenzberg M, Schellekens
H. Expert Opinion Biol Ther. 2012;12:1473-85
5.

Biosimilars in the EU - Information guide for healthcare professionals (europa.eu)

Statement on the scientific rationale supporting interchangeability of biosimilar
medicines in the EU
EMA/627319/2022

Page 3/3