Tony Hagen is senior managing editor for The Center for Biosimilars®.
Simplified standards for biosimilar approvals in the United Kingdom may open the door to broader changes.
Responding to increasing calls to do away with comparative clinical efficacy trials for biosimilar candidates, based on the contention these studies are largely unnecessary, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has issued draft guidance for a reduction in such data requirements.
In most cases, a comparative efficacy trial would not be needed; however, such a determination must be supported by robust evidence and would be made only after consideration of all other elements of an application for biosimilar approval, the draft guidance states.
The draft document follows a recent position paper from members of the MHRA arguing that, except in rare cases, biosimilarity to a reference product (RP) can be demonstrated by analytical testing and a pharmacokinetic (PK) trial. Under the system they propose, comparative efficacy trials would be “reserved for exceptional circumstances.”
Guidance Accompanies Transition
The draft guidance follows a transition under which the MHRA would become a regulator in its own right with complete authority over evaluation and approval of all medicinal products for use in the United Kingdom. This change takes effect on January 1, 2021.
The MHRA transition is related to the United Kingdom's exit from the European Union. Until now, the United Kingdom has followed guidelines on medicine approvals from the European Union's Committee for Medicinal Products for Human Use. According to the MHRA, the waiver of comparative clinical efficacy trials has already been "allowed for certain biosimilar products in the [European Union] but has not yet been applied to complex biosimilar products, such as monoclonal antibodies."
Part of this transition of authority in the United Kingdom involves creation of a streamlined pathway for the approval of innovative drugs that incorporates ongoing, postmarketing analysis of outcomes based on real-world evidence and novel clinical trial designs.
Whereas the United States and European Union do currently require the use of comparative clinical efficacy trials for biosimilar approvals, members of the MHRA, in their position paper, contend that these studies add little to the quality of evidence garnered by analytical testing, in-human PK, and pharmacodynamic studies. Technological advances over the past 10 years have made efficacy trials largely redundant, they contend.
Recently the International Generic and Biosimilar Medicines Association (IGBA) concurred with this opinion, also calling upon global regulatory authorities to simplify the biosimilars approvals process in order to do away with redundancies and avoid unnecessary use of time and resources. IGBA is a trade association representing biosimilar producers.
According to the MHRA draft guidance, comparative efficacy trials are “not considered necessary,” but “a well-argued justification for the absence of an efficacy trial” must be included with an application for biosimilar approval. “The efficacy of the RP can usually be derived from its [mechanisms of action],” the guidance states.
The draft guidance also notes that a biosimilar will be considered interchangeable with a RP once the biosimilar is authorized by the MHRA, but only with the prescriber’s approval in consultation with the patient. Pharmacy level substation without prescriber approval would not be allowed for biosimilars, under the guidance.
In the United States, interchangeable status, which allows free use of either a biosimilar or RP for a given indication, is not automatically granted, but requires additional evidence.
“Switching patients from one product to another (RP or biosimilar) has become clinical practice,” the UK regulators state. “The decision rests with the prescriber in consultation with the patient….No safety signal has been detected in more than a decade of experience with switching.”