QA/QC Strategy for Biologics and Biopharmaceuticals
In the eyes of regulatory authorities, the quality issues of biologics are definitely different from chemical drugs because of: (1) use of living source materials to produce the biologic, (2) increased complexity of biologic manufacturing processes and (3) increased complexity of the biologic molecules themselves. While chemical drugs can become generics, biologics products are best viewed as biosimilars, and not as bio-generics.
Biologics are highly susceptible to adventitious agent contamination – prions, viruses, mycoplasmas, and bacteria/fungi microbes. Risk control procedures – such as barriers to entry, testing to confirm absence, and inactivation/removal – are essential. Lessons can be learned from reported contaminations of biologic manufacturing processes. Compared to chemical drugs, biologics have a more complex process-related impurity safety profile, especially due to the living system-related impurities (e.g., host cell proteins, host cell DNA).
Extensive physicochemical characterization of protein and monoclonal antibody molecular structure, employing multiple, complementary, as well as orthogonal, state-of-the-art analytical methods is necessary, covering primary amino acid sequence changes (e.g., truncation, deamination, oxidation), post-translational modifications (e.g., glycosylation), and higher order structural changes (e.g., secondary folding, aggregation). Because of the molecular structural complexity of a biologic, including its many possible structural variants, functional activity assays are required that can discern which structures have what amount of potency. While bioassay functional activity assays (i.e., in vivo, in vitro) are required for measuring potency, surrogate (analytical) assays can be used if properly correlated to the bioassays. At times, an assay matrix may even be required. Many manufacturers underestimate the amount of resources and time needed to properly implement these functional activity assays.
This course will help the attendee to develop an effective QA/QC quality risk management strategy for biologics, addressing the quality challenges all the way from Phase 1 clinical studies through commercialization. Guidance from the FDA, EMA and ICH will be discussed. In addition, the differences in managing quality for chemical drugs vs biologics will be examined.
This course has been pre-approved by the Regulatory Affairs Professionals Society (RAPS) as eligible for 12 credits towards a participant's RAC recertification upon full completion.
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CfPIE is a preferred provider and offers MichBio members a 15% discount on course registration fees. Click here for more information.