Next year, the UK will conclude its transition from the EU, with the regulation of all medicines and devices to be transferred from EMEA to the UK's Medicines and Healthcare products Regulatory Agency (MHRA). This new regime will apply from 01 January 2021, and will involve some significant changes.
Biosimilars will now be regulated by the Human Medicines Regulations 2012 (UK), as amended by the Human Medicines (Amendments etc)(EU Exit) Regulations 2019 (UK). Guidance published by the MHRA in October provides a summary of the new regime for biosimilar licensing.
Reference Medicinal Products
Reference Products (RPs) should comply with Regulation 48 of the Human Medicines Regulations 2012 and can include:
products with a UK authorization authorised for at least 8 years (including those converted from an EU marketing authorisation);
products with an EU marketing authorisation (MA) at the end of the transition period but not converted into a UK product license (MA holder opted out of the process); and
products with an EU marketing authorisation that ceased to be in force before the end of the transition period for reasons not relating to quality, safety or efficacy.
Where a non-UK RP is used, evidence should be provided that the RP is representative of the UK RP, and must be authorised in a country with similar scientific and regulatory standards such as EU/EEA countries, Switzerland, USA, Canada, Australia or Japan.
Significantly, any data and market exclusivity to which the RP was entitled prior to exiting the EU will continue to apply.
Streamlined Clinical Trials
In most cases, a comparative efficacy/safety trial will not be necessary. A justification for not conducting this trial should be provided with the application, establishing:
that comparable efficacy can be derived from comparable binding properties and functional characteristics: and
the quality attributes and formulation of the biosimilar candidate form the basis that safety and immunogenicity are comparable to those of the RP.
A comparative efficacy/safety trial will still be required in cases where the main mechanism of action (MOA) of the RP is not known, where it is difficult to predict the impact of analytical differences which have not been resolved by adaptations to the manufacturing process and where safety uncertainties cannot be resolved without patient exposure pre-licensing.
Once a biosimilar has been shown to be highly similar to the RP in terms of analytical characteristics and functional properties, all the indications granted to the RP can be claimed by the biosimilar candidate without further justification.
While the summary of product characteristics (SmPC) for the RP serves as a base for the biosimilar label, differences in indications resulting from the strength or pharmaceutical form of the biosimilar are to be clearly delineated. The MHRA has provided the following exemplary language:
“[Invented Name] is only available as [description of the pharmaceutical form]. Thus, it is not possible to administer [Invented Name] to paediatric patients that require less than a full [X] dose. If an alternate dose is required, other medicinal [INN] products offering such an option should be used.”.
Once approved, the biosimilar is considered interchangeable, but must be prescribed by brand name. Substitution at the pharmacy level without consulting the prescriber is not permitted for biological medicines.