From the end of the Brexit transition period (1 January 2020), the licensing of biological products (including biosimilars, advanced therapy medicinal products), and how the status of plasma master files and vaccine antigen master files, will be provided for by the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019.
In September 2020, the UK government provided guidance in relation to biological products: Guidance on licensing biosimilars, ATMPs and PMFs from 1 January 2021. However, in relation to biosimilar products specifically, further guidance was considered likely to be necessary and the form and detail of this has been put out to consultation in relation to the licensing of biosimilar products post-transition – see the consultation document here: MHRA draft guidance on the licensing of biosimilar products.
The draft guidance under consultation largely adopts the existing principles in the various Committee of Medicinal Products for Human Use (CHMP) guidelines concerning biosimilars, but incorporates some amendments, namely relating to:
- Reference products
Applications for biosimilar products made after 1 January 2021 must be made with reference to a product that has been authorised in the UK for at least 8 years, and includes products authorised in the UK and by conversion from EU marketing authorisations. It is also possible to use a non-UK reference product, including products that had an EU marketing authorisation at the end of the transition period but did not convert to a UK marketing authorisation. Non-UK reference products can be used where evidence is provided that the non-UK reference product is representative of the UK reference product with suitable analytical bridging data. Data and market exclusivity period entitlements for reference products approved before the date of EU exit will continue to apply in the UK.
- Lack of requirement for in vivo studies in animals
The draft guidance states that in vivo studies from animals are not required to be submitted “as these are not relevant for showing comparability between a biosimilar candidate and its [reference product]”. Such in vivo studies would include pharmacodynamics studies, kinetic studies and toxicity studies (unless, for the latter, results have been generated in compliance with Good Laboratory Practice). The guidance further states where there are differences between a biosimilar candidate and the reference product that may have a clinical impact, it should be considered whether the product be developed as a new biological product, rather than a biosimilar. Specifically, data from in vivo studies in animals would not be able to address any such differences and therefore should not be submitted for this purpose.
- Change in the requirement for a comparative efficacy trial in most cases
For applications from 1 January 2021, the draft guidance states that a comparative efficacy trial will not be required in most cases. Applicants should include “a well-argued justification for the absence of an efficacy trial” in the submitted application. The guidance indicates that the efficacy of the reference product used for the biosimilar candidate can usually be derived from its mechanism of action. Therefore, applicants should provide information regarding the binding properties and functional characteristics of the biosimilar candidate as compared to the reference product, and accounting for an differences. The draft guidance anticipates that there will be some cases where a comparative efficacy trial will be required, such as where the mechanism of action of the reference product is not known.
The draft guidance further addresses:
- excipient(s) in the proposed biosimilar product: the use of different excipients to those used in the reference product is not encouraged. Where there are differences, the safety of the different excipient should be addressed in the application.
- indications claimed by a biosimilar product: the draft guidance states that once a biosimilar candidate has been shown to be highly similar to the reference product in terms of analytical characteristics and functional properties related to the mechanism of action, the indications granted to the reference product can be claimed by the biosimilar candidate. The draft guidance further makes clear that, save for some specific examples of dosage differences or other scientific reasons, the Summary of Product Characteristics (SmPC) for the biosimilar must be the same as the reference product.
- interchangeability of the proposed biosimilar product, once authorised, with the reference product: the guidance highlights that once authorised, the biosimilar will be considered interchangeable with the reference product. However, it notes that although switching patients (either between the reference product and the biosimilar, or between biosimilars) has become clinical practice, as biosimilars must be prescribed by brand name, the decision on whether there is switching rests with the prescriber in consultation with the patient. Substitution of the prescribed product with another without consulting the prescriber is not permitted.
The consultation closes on 15 November 2020. Submissions can be made directly to the MHRA.