Intertek Pharmaceutical Services
Abstract: At Intertek, we provide regulatory-driven, phase-appropriate, CMC laboratory and GMP analytical services. Our expertise ensures sufficient information for your filings through expert method development and validation, stability studies and GMP batch release testing for complex drug delivery, in particular inhalation, and formulation across both small and large molecules. To meet biopharmaceutical development milestones and comply with regulatory requirements safety assessment is paramount, as slight changes in the structure, physico-chemical properties, potency and impurity profile of a biologic can provoke an adverse immune response. In this poster we deploy Complement Dependent Cytotoxicity Assays (CDCC) and Antibody Dependent Cell Cytotoxicity (ADCC) potency assays to assess a monoclonal antibody biosimilar. Both assays are robust, reproducible and can be used to monitor changes in the biological functionality due to changes in the protein confirmation.
Description: Cell-based potency assays are important for establishing safety and efficacy profiles for biopharmaceuticals and in particular to support lot release and stability testing for products such as biosimilars and monoclonal antibodies as they measure the biological function of the drug against a known, characterized reference standard. This is a critical quality attribute and measurement of potency plays an essential role in quality control, product release and stability studies. The method/type of potency test employed is specific to the mechanism of action (MOA) of the biologic therapeutic being studied. Some biologics have multiple MOAs, and so multiple assays may be needed to sufficiently demonstrate product efficacy as well as lot-to-lot comparability. Monoclonal antibodies such as Rituximab are an example of a product with multiple MOAs. These molecules are the fastest growing class of biological therapeutic on the market and are complex in nature which means that novel, flexible approaches to designing and executing potency assays are sometimes required in order to assess their multiple MOA.
At Intertek, our potency testing experts apply tailored bioassays for molecules such as biosimilars, peptides, monoclonal antibodies, growth factors, hormones and cytokines. In this poster we assess the activity of Rituximab which is a monoclonal antibody therapeutic marketed as MabTheraTM (or Rituxan in the United States, Japan and Canada) (Roche). The patent expiry for this product in the EU was Nov 2013 however in the USA the patent on the drug expires in 2018. Rituximab Complement Dependent Cytotoxicity Assays (CDCC) and Antibody Dependent Cell Cytotoxicity (ADCC) potency assays are used to determine the relative potency of a product by comparing the biological response/activity, related to its mode of action, with a control/reference preparation. This helps to fully understand the mechanisms of action in order to demonstrate comparability to the innovator. Both assays are found to be robust, reproducible and can be used to monitor changes in the biological functionality due to changes in the protein confirmation. By applying a multiple assay approach with selection from an array of cell based assay platforms/models, as well as physico-chemical assays, product development and quality control of biologics can be thoroughly supported.
Alternative resource: http://www.intertek.com/pharmaceutical/
Category: Drug Product
Type: Biologics
Contact: Ashleigh Wake, Director of Biological Services, Intertek Pharmaceutical Services ([email protected])