EU: Revision of EMA quality guideline regarding biosimilars


On 7 February 2011 the EMA released a concept paper for consultation on the revision of the quality guideline on Biosimilars (Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues, EMEA/CHMP/BWP/49348/2005).

The guideline addresses what steps should be taken to show quality during the demonstration of comparability for Similar Biological Products containing recombinant DNA-derived proteins. It particularly provides guidance on:

(i.) the manufacturing process;
(ii.) differences in impurity profiles and product-related substances;
(iii.) the choice of the reference product; and
(iv.) the analytical methods and procedures used for the comparative testing.

The current version of the guideline addresses the comparability exercise of the biosimilar against the reference product but not the comparability exercise for manufacturing process changes, either during development or post-authorisation. Since the guideline was published, this has been recognised to as an area where guidance is necessary. Changes to the manufacturing process for both the reference products and the biosimilar products are frequent, and such changes can have a significant effect on the quality profile.  Therefore, as the quality profiles of the reference and biosimilar products evolve, the results of the initial comparability exercise between the two may no longer be accurate.

The EMA’s Biologics Working Party has therefore recommended in this concept paper that the current guideline be revised to ensure that the evolution of the quality profiles of both reference products and the similar biological medicinal products is captured throughout their respective lifecycles.

The deadline for comments on the concept paper EMA was 31 May 2011. It is anticipated that the draft revised guideline will be released for consultation in the last quarter of 2011.

A potential development from this recommended revision may be a step towards strategic manufacturing process revision by manufacturers of original reference products, in order to increase the comparability burden that rests on the manufacturer of a biosimilar at present.