EMA shares lessons learned from biosimilars pilot

Regulatory NewsRegulatory News | 19 October 2021 |  By 

The lack of mature quality data, such as sufficient batch data, hindered the ability of the European Medicines Agency (EMA) to provide scientific advice to sponsors on their biosimilar development programs, according to a report on the agency’s recently concluded biosimilar scientific advice pilot.
Also, EMA found that current regulatory guidelines, which assume that developers will take a stepwise approach to biosimilar development where clinical studies are conducted before analytical comparability studies, do not reflect current industry trends where clinical studies are conducted in tandem with analytical comparability studies.
The scientific advice program was launched in February 2017 to advise developers of biosimilars on the studies they should conduct, based on a review of available quality, analytical and functional data and to explore the stepwise approach to biosimilar development. (RELATED:  EMA to Launch Tailored Biosimilar Scientific Advice Pilot, Regulatory Focus, 16 December 2016)
EMA’s human medicines committee (CHMP) and the biologics and biosimilars working groups of the Scientific Advice Working Party (SAWP) recognized that tailored advice earlier in the biosimilars development process could help EMA decide whether, in some cases, a clinical efficacy and safety trial could be waived. The goal, according to the background section of the report, was to “further advise on the next steps of the development programme thereby further supporting the development of a biosimilar in a targeted way.”
The pilot covered six scientific advice requests from four applicants. One requested advice on two separate development plans, and one requested initial and follow-up advice on the same development plan. All requests came from sponsors interested in developing monoclonal antibodies, and one was a small/medium size enterprise (SME).
Another eight applicants requested information and expressed a desire to participate in the pilot. During the period that the pilot was being run, EMA received 71 requests for standard advice on biosimilar development programs.
The advice sought by developers went beyond strategy recommendations; applicants wanted advice that “went further to provide scientific advice on the analysis of the data presented,” noted EMA in the report.
Some of the topics covered in the requests included waiving pre-clinical studies; the appropriateness of the analytical methods; whether the clinical development program could be reduced based on additional quality data; whether it would be possible to have broadened equivalence margins based on available data; and for data to be evaluated to determine any other remaining gaps in the biosimilar development program.

Industry appreciated the review
EMA said that pilot participants “appreciated the possibility to present and discuss with regulators their quality comparability data” and deemed this advice “very important to gain clarity and confidence in their programme.”
Yet the lack of mature quality data, such as having sufficient batch data, compromised EMA’s ability to provide scientific advice.
“The maturity of the quality data appeared to be the biggest challenge in reaching the goals of the pilot,” said the report. “The pilot brought the insight that quality and clinical development often take place in parallel rather than in a stepwise manner. Hence in some cases the quality data were rather immature (e.g. from a limited number of batches and/or not obtained with material from the proposed commercial process), which made recommendations regarding a tailored clinical development (patient size, population, efficacy margins, etc.) difficult.”
There were exceptions: One product entered the pilot twice and the second submission had a more “mature and comprehensive data package.”
A further insight gleaned from the pilot is that “a mature set of quality comparability data is often achieved at later phases in the biosimilar development.” While the current regulatory approach calls for a stepwise approach where clinical studies are conducted before generating analytical comparability data, this “is not necessarily employed in practice where clinical studies are often conducted in parallel with generation of analytical comparability data.”
Slow uptake
Another learning: EMA said that although the program was successfully enrolled applicants and finalized the pre-specified number of scientific procedures, “initial uptake was slower than expected.” The program was not completed until April 2020.
Yet the agency noted that “this is not unusual for new types of engagement opportunities.”
Respondents were also asked to rate the quality of the advice they received. On a scale of one to five, with five being the highest rating, industry gave EMA an average rating of 3.7 for the clarity of the advice received and 3.5 for comprehensiveness of the advice. Industry gave EMA an overall score of 3.7 on whether their expectations were met for scientific advice.
EMA report on biosimilars pilot


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Tags: biosimilars, EMA

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