Development and Validation of Bioanalytical Assays for Biologics: Quantification (PK) and Immunogenicity Assays

Part 1: Quantitation Assays

Quantitation assays are critical for the development of biologics and biopharmaceuticals as well as accurate detection of protein biomarkers. Immunoassays for quantitation of protein drugs in biological matrices (ex. plasma, serum, tissue) generally take much longer to develop and are subject to a wider range of interferences than traditional xenobiotic small molecule quantitation assays by LC-MS/MS. Part 1 of this interactive two day course focuses on these critical assays and will take you step-by-step through the development of quantitation assays for proteins including monoclonal antibodies.

The course begins with basic development, highlighting technical requirements, regulatory requirements and industry trends. We start by detailing how to select and maintain critical reagents, then move to assay formats. This includes understanding physical processes behind the four parameter model and how to interpret curve shape in terms of assay optimization. Then we move into qualification and validation of the assays to support pre-clinical and clinical studies. Part 1 of this course ends with preparation of the assay for use in a bioanalytical laboratory, including validation, establishing robustness, determining acceptable and practical system suitability criteria and suggestions for long term maintenance of the assay.

Part 2: Immunogenicity Assays

Part 2 of this course starts with an overview of immunology followed by the requirements of an immunogenicity program, including the establishment of a tiered testing approach for screening, confirmation assay analysis, titer assays and neutralizing antibody assays. The course then goes on to cover basic development of these assays, highlighting how to develop and label critical antibody reagents, different assay formats (ex. bridge, sandwich), including an analysis of strengths and weaknesses of each format. This is followed by a review of current scientific guidelines on how to establish cut-points (with a hands on calculation workshop with sample data at the end of the course). Optimization of screening assays to improve sensitivity and minimize outliers is also reviewed. The sensitivity of various assays to drug (assay drug tolerance) will be discussed and an overview of available technologies and sample pre-treatment approaches will be reviewed. Then we move into validation of the assays to support pre-clinical and clinical studies. The course will end with concepts of risk based testing approaches.

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.

Dr. Robert Dodge has worked in the Pharmaceutical Industry for 20 years in both CMC manufacturing of Biologics and Bioanalytical testing of Protein Drugs and Biomarkers. Dr. Dodge was Director of Immunochemistry and Cell Biology at the Pharmanet Development Group, a contract research laboratory specializing in bioanalytical assay development and sample testing. His group developed assays for drug quantitation, immunogenicity testing and biomarker detection. Before this, he was co-founder and Laboratory Director at Princeton Bio Lab. This GLP/GMP-compliant contract research laboratory specialized in cell-based assays for protein therapeutics and was sold to Pharmanet in 2007.

Previously, Dr. Dodge spent 10 years at Bristol-Myers Squibb. Starting in the Immunology Department of the Pharmaceutical Research Institute, he later moved into biologic drug development and characterization. While there, he developed bioassays, neutralizing antibody assays and ligand binding assays. He also characterized biologic drugs, developed biomarker assays, interacted with the FDA regarding regulatory filings and managed a staff of scientists.

Dr. Dodge received his Ph.D. from Cornell University, where he also completed an NIH post-doctoral fellowship.