Analysis of Post-Change Comparability and PEGylation Among Biotech CMC Concerns Drawing FDA Comment at AAPS National Biotech Conference

The expectations for pre- and post-change lot comparisons and for PEGylation analysis were among FDA CMC application filing concerns addressed by CDER Office of Biotechnology Products (OBP) official Susan Kirschner at an “ask the regulator” session at AAPS’ National Biotech Conference in late May in San Diego, California.

Intended to probe into some of the issues on which firms are looking for more clarity in putting together CMC applications for biotech and other biological products, the questions to which Kirschner responded had been submitted to the agency in advance of the meeting by the association’s Protein Aggregation and Biological Consequences Focus Group.

In addition to OBP’s expectations for comparability studies and PEGylation, the focus group sought clarification regarding: ● the promotion of new analytical technologies ● preference of technologies for examining sub-visible particles ● surfactant specifications ● stability testing of sterile filtered bulk drug product ● the use of disposables in manufacturing ● assessment of leachable accumulation, and ● expectations for characterization of what happens to biomolecules after injection.

While some of the questions were not the type that lend themselves to easy answers, Kirschner made an effort to give succinct responses and to summarize current agency thinking on key areas of concern.  She serves as Associate Chief of OBP’s Immunology and Therapeutic Proteins Laboratory. (Kirschner’s responses to all the questions posed by the AAPS committee are provided below.)

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