MHRA Guidance on Licensing Biosimilar Medicinal Products in the UK

Overview and Legal Basis

In Great Britain (England, Wales and Scotland), biosimilar products are biological medicines developed to be highly similar to an already authorised reference biological product (originator). The MHRA evaluates biosimilars on a case-by-case basis using a totality-of-evidence approach. Applicants must demonstrate similarity in quality, safety and efficacy through comprehensive comparative data. The guidance aligns with principles in the Human Medicines Regulations 2012 (as amended) and reflects international standards (e.g., WHO, EMA, ICH). It was last updated to reflect post-Brexit arrangements for GB. Guidance on the licensing of biosimilar products - GOV.UK

Definition and Key Principles

A biosimilar is a biological medicinal product highly similar to another already authorised biological product (reference product) with no clinically meaningful differences in terms of quality, safety or efficacy. Key principles include:

• Comparability exercise at the quality level is essential.
• Similarity must be demonstrated through analytical, non-clinical and clinical studies.
• Reduction in non-clinical and clinical data may be justified if robust quality comparability is shown.
• Extrapolation of indications is possible when scientifically justified.

Stepwise Approach to Development

The development follows a stepwise process:

1. Quality Comparability: Extensive analytical characterisation comparing physicochemical and biological properties (structure, purity, potency, etc.).
2. Non-clinical Studies: Pharmaco-toxicological assessment, typically in vitro and in vivo where needed; reduction possible if quality similarity is strong.
3. Clinical Studies: Pharmacokinetic (PK) and pharmacodynamic (PD) studies are mandatory; at least one comparative efficacy/safety study in a sensitive population/model is required. Immunogenicity must be assessed.

If similarity is convincingly demonstrated at each step, the need for certain studies may be waived or reduced.

Extrapolation of Indications

Extrapolation to other indications of the reference product is acceptable if:

• Similarity is convincingly shown in a sensitive indication.
• The mechanism of action and target receptor are the same.
• Comprehensive comparability data support it.
• Any differences are appropriately justified.

The applicant must provide a scientific rationale, and the MHRA assesses on a case-by-case basis.

Interchangeability and Substitution

The MHRA does not use the term “interchangeable” for biosimilars. Automatic substitution at pharmacy level is not currently permitted in the UK; decisions on switching are made by prescribers. Biosimilars are identified by brand name and batch number to support traceability.

Post-Authorisation Requirements

• Pharmacovigilance: Enhanced monitoring for immunogenicity and other safety signals.
• Risk Management Plan (RMP): Required, with specific focus on biosimilar-related risks.
• Periodic Benefit Risk Evaluation Reports (PBRERs): Submitted as per standard requirements.
• Traceability: Use of brand name and INN with manufacturer identifier.

Naming and Labelling

• Biosimilars use the same international non-proprietary name (INN) as the reference product.
• The product should be clearly identified by brand name and batch number in prescribing and dispensing.
• Labelling must indicate it is a biosimilar and reference the originator.

Practical Considerations for Applicants

• Engage early with MHRA via scientific advice to discuss development plans, comparability strategy and potential waivers.
• Provide comprehensive justification for any data reductions or extrapolations.
• Ensure robust immunogenicity assessment throughout development.
• Prepare for post-authorisation commitments, including real-world evidence collection if needed.

This guidance supports efficient development of biosimilars while maintaining high standards of safety, quality and efficacy for patients in Great Britain. Guidance on the licensing of biosimilar products - GOV.UK