By Jianmei Kochling and Henriette Kuehne
A vital aspect of the structural characterization of biologic products is the identification of stability-indicating attributes and the development of well-characterized, robust methods for inclusion in the stability program. Design of these programs presents a particular challenge for biosimilars, because comparative stability to the reference product must be evaluated in addition to stability of the sponsor’s product. Complicating factors to comparative stability studies are the need to source a sufficient number of originator lots, the lack of knowledge regarding lot independence and lot age, and the need to employ characterization methods that can assess both the variants present in the biosimilar but also potential low-level variants present only in the originator.
In addition to typical stability-indicating methods (e.g. those that evaluate impurities), additional methods may be needed to demonstrate a long-term match of the total molecular fingerprint. Attributes and methodologies of particular interest for this purpose include but are not limited to: evaluation of secondary/tertiary fold and epitope accessibility; potential for aggregation through disulfide scrambling and misfolding; post-translational modifications, including site specific glycosylation; and charge-variant profiles.
The AAPS Biosimilars and Stability focus groups will jointly present the scientific forum Applications of Molecular Fingerprinting to Stability of Biosimilar Products at the 2016 AAPS National Biotechnology Conference, May 16–18, in Boston. The scientific forum will explore how to determine which methods are critical to establish a unique pattern, how molecular fingerprints may change over time, and how to select methods to include in a robust biosimilar and comparative reference product stability studies, including how methods historically used in characterization may be useful in establishing a comprehensive stability profile. Special attention will be given to the depth and breadth required of a solid comparative stability, as well as the associated challenges. This discussion is of particular interest to those who are concerned about the stability of biosimilars and is also relevant to originator drugs.