UK finalises biosimilar guidance designed to improve on EMA starting point

As the end of the Brexit transition period approached last year, the MHRA released draft guidance on the licensing of biosimilars for consultation. The draft document was based on the European Medicines Agency (EMA) guidelines that applied in the UK before Brexit, but it diverged from those foundational texts in some areas.

In describing the ways in which the draft differed from the EMA’s position, the MHRA highlighted the lack of a requirement for in vivo studies in animals and changes in the requirement for a comparative efficacy trial in most cases. The MHRA said the changes reflected experience gained with biosimilar monoclonal antibodies and fusion proteins since 2013 but some people needed convincing of the merits of its position.

According to the MHRA, “a few respondents [to the consultation] questioned the basis for not requiring confirmatory clinical efficacy and in vivo animal studies.” The MHRA responded to the questioning by providing links to peer-reviewed publications that contain evidence to support its position. 

Overall, the MHRA maintained its position in the face of the questioning, although it did soften some of its language. The final guidance states that “although each biosimilar development needs to be evaluated on a case by case basis, it is considered that, in most cases, a comparative efficacy trial may not be necessary if sound scientific rationale supports this approach​.”

The draft guidance contained the more direct statement “in most cases, a comparative efficacy trial is not considered necessary​” but the end result is still that the MHRA will allow biosimilars to come to market without a confirmatory efficacy study.

Plans to allow biosimilars to market in the absence of in vivo data from animal studies proved to be less contentious. The final text, like the draft version, says “no in vivo studies from animals are requested as these are not relevant for showing comparability between a biosimilar candidate and its [reference product]​.”

The MHRA has made changes to other parts of the document in response to the feedback it received during the six-week consultation last year. Some of the changes relate to comments from two patient organisations.

The organisations asked for factors that are important for patients are considered in the guidance. The MHRA responded by changing its position on points such as divergence from the excipients used in reference products, which was discouraged in the original draft but embraced in some contexts in the final guidance.

“Changes which may benefit patients (for example, to reduce injection pain or stinging) are encouraged and should be carefully considered​,” the MHRA wrote in the final guidance.

The MHRA’s receptiveness to the patient feedback happened against the backdrop of an effort by the agency to change its approach in light of an independent, government-commissioned review that found it needs to engage more with patients and their outcomes.