Da Yu Protein Sciences – Protein Characterization
Protein characterization is a critical part of CMC development for any therapeutic protein (i.e., a Biologic). Modern biotechnology has enabled the development of well-characterized biologics, which includes monoclonal antibodies and recombinant proteins. The CMC packages for these therapeutic entities are reviewed in the FDA by the Center of Drug Evaluation and Research (CDER) in the Office of Biotechnology Products. From a regulatory perspective, full characterization describes the chemical, physical and functional attributes of a protein. Circumstances where protein characterization of a Biologic is indispensable in the regulatory environment include the following:
IND Submissions – As part of the CMC section of an IND submission, regulatory agencies expect the sponsor to describe the chemical, physical and functional characteristics of the drug substance. Sponsors are also expected to describe stability studies for the drug substance and the drug product. Characterization of protein therapeutics under various environmental conditions (e.g., pH, temperature) provides insight into potential stability-indicating assays, which are a critical part of a Biologic’s stability program.
Specifications - Many specifications set during CMC development are based on thorough Biologic characterization. According to ICH guidelines (Q6B), “Characterization of a biotechnological or biological product…by appropriate techniques is necessary to allow relevant specifications to be established.”
Quality By Design (QbD) - QbD principles emphasize both process and product understanding. One of the outcomes of utilizing a systematic approach, such as QbD, to develop a manufacturing process is that it can produce a design space. Operating anywhere within the design space is not considered a manufacturing change and therefore it does not require regulatory review. In order to achieve this regulatory flexibility, sponsors should have enhanced knowledge about their Biologic’s characteristics throughout the design space. Thus, protein characterization conducted within a range of multiple manufacturing options and process parameters supports what is eventually designated as the design space.
Comparability Testing – When a manufacturing process for a Biologic changes, whether during clinical development or post licensure, regulatory agencies require a sponsor to perform comparability testing. Product comparability may depend on the physical, chemical and functional characterization of the Biologic before and after manufacturing changes as a first step to ensure the product remains safe and efficacious. Extensive side-by-side characterizations of the product before and after manufacturing changes showing comparability are advantageous to the sponsor. The critical importance of comparability testing is undeniable. A sponsor’s ability to demonstrate comparability to regulatory agencies may abrogate the need for clinical trials to reaffirm safety and/or efficacy after the manufacturing process changes.
Biosimilar Development - When a sponsor submits a Biologics License Application (BLA) to the FDA for a biosimilar it should include extensive analytical laboratory studies (i.e., physical, chemical and functional analyses) demonstrating the Biologic is “highly similar” to the licensed reference product. The submission should include a comparison of all relevant characteristics of the biosimilar and the reference product including assessment of the primary, secondary, tertiary, and quaternary structure as well as other chemical and functional characteristics. Regulatory agencies prefer a multitude of assays measuring the same product attribute (i.e., orthogonal assays) to provide separate and independent confirmation of biosimilarity.
Da Yu Protein Sciences provides a spectrum of protein characterization services including:
- Physical analyses utilizing Circular Dichroism Spectroscopy, UV Derivative Spectroscopy and Differential Scanning Fluorimetry.
- Chemical analyses such as Amino Acid Composition and Extinction Coefficient Determination.
- Functional analyses including ELISA, Michaelis-Menten Enzyme Analysis and Ligand-Binding Assays.
Clients interested in discussing these capabilities or any other protein characterization needs are encouraged to Contact Us.