The Medicines and Healthcare products Regulatory Agency (MHRA) has updated its guidance on the "Licensing of Biosimilar Products" in the UK, incorporating recent regulatory changes, including the Windsor Framework. The guidance focuses on the development, approval, and licensing of biosimilars, ensuring safety, efficacy, and consistent quality while aligning with global best practices.
Released on 20 December 2024, the update provides clarity on regulatory requirements for biosimilar products and removes Advanced Therapy Medicinal Products (ATMPs) and Veterinary Master Files (VMFs), now addressed in separate guidelines.
Biosimilars are biological medicines highly similar to already approved reference products. Unlike generic drugs, biosimilars have inherent variability due to their complex biological nature, but they exhibit no clinically meaningful differences in terms of safety, efficacy, and quality when compared to the reference product.
The guiding principle of a biosimilar development programme is to establish similarity between the biosimilar and the RMP based on a comprehensive comparability exercise, ensuring that the previously proven safety and efficacy of the RMP also apply to the biosimilar.
This guidance outlines the regulatory framework for biosimilar licensing in the UK, covering:
Requirements for biosimilar development.
Comparative studies to demonstrate biosimilarity.
Licensing processes for biosimilar products.
The guidance ensures alignment with international guidelines while integrating UK-specific provisions under the Windsor Framework for products marketed in Northern Ireland. Under the Windsor Framework, biosimilar products marketed in Northern Ireland must comply with EU regulatory standards, while products marketed in Great Britain are subject to MHRA-specific requirements. Separate submissions may be necessary to ensure compliance across both regions.
The guidance emphasizes the following core aspects:
A. Reference Product
The reference biological product must have a valid marketing authorisation in the UK or EU.
B. Comparability Studies
Biosimilarity must be established through a comprehensive comparability exercise, addressing:
Quality Comparisons: Analytical characterization of molecular structure, purity, and activity.
Non-Clinical Comparisons: Pharmacokinetics (PK) and pharmacodynamics (PD) studies, if required.
Clinical Comparisons: Safety, efficacy, and immunogenicity assessments in patients.
C. Immunogenicity Testing
Manufacturers must provide robust data on the immunogenic potential of the biosimilar.
The MHRA adopts a stepwise approach to biosimilar development:
Step 1: Analytical and structural characterization of the biosimilar against the reference product.
Step 2: Functional assessments to confirm biological activity.
Step 3: Clinical trials to demonstrate equivalence in safety and efficacy.
The extent of clinical data required depends on the robustness of analytical and functional evidence.
Applications for biosimilar products must be submitted via the MHRA Submissions Portal in eCTD format.
Fees vary depending on the product type and complexity.
Fast-track or rolling review pathways may be available for biosimilars addressing critical public health needs.
For more details, refer to the full guidance:
Comments