Development and Validation of Bioassays: Potency and Immunogenicity

Learning Objectives

Upon completion of this course, attendees will have a clear understanding of regulatory agency expectations and will have gained the background knowledge necessary to effectively plan bioassay assay validation programs for both QC release potency assays and bioanalytical/GCLP immunogenicity assays for both marketed products and products still in clinical development.

Participants will develop expertise in writing protocols and reports and setting acceptance limits for bioassay method validation. Participants will have acquired insight into how to avoid common validation pitfalls and be able to quickly discriminate compliant from non-compliant validation activities. In addition, attendees will gain practical experience in applying what they have learned during a validation workshop.

Course Description

Part 1: Potency Assays

Biological assays are critical for the development of biologics and biopharmaceuticals.  Many companies find themselves on clinical hold because of poorly-developed and inadequately validated potency assays.  Part 1 of this interactive three day course focuses on these critical assays and will take you step-by-step through the development of biological potency assays.

The course begins with basic development, highlighting technical requirements, regulatory requirements and industry trends.  We start by detailing how to select and maintain critical rare reagents, then move to format issues.  This includes hints on how relative potency assays are run, the number of dilutions required, selecting number of replicates, and best approaches for potency calculations.  Then we move into characterization of the assays to support phase I, II and III clinical studies.  Part 1 of this course ends with preparation of the assay for use in a quality control laboratory, including validation, establishing robustness, determining acceptable and practical system suitability and hints for long term maintenance of the assay.

Part 2: Immunogenicity Assays

Immunogenicity assays are critical analytical methods which need to be developed early in the product development cycle.  During the past decade these assays have become the most hotly debated methods run on clinical samples.  Product approvals are often delayed because of a poor understanding of immunogenicity assay requirements.  This course will help you avoid the common pitfalls of these complex methods. 

Part 2 of this course starts with a review of the requirements of an immunogenicity program, including the establishment a three-tier testing approach for screening, positive confirmation assay analysis and neutralizing capability determinations.  The course then goes on to cover basic development of these assays, highlighting how to develop critical rare reagents. Different assay formats, including an analysis of strengths and weaknesses of each, is also covered.  This is followed by  advice on how to establish positive/negative cut-offs, and improve sensitivity while maintaining throughput. The sensitivity of various assays to circulating drug will be discussed and an overview of available technologies and sample treatment approaches will be discussed. Then we move into validation of the assays to support phase I, II and III clinical studies. 

The course will end with preparation of the assay for use in a clinical screening laboratory. This includes an in-depth look at how the assay needs to be run, the writing of the clinical report, which of the GXPs are applicable in each of the ICH regions and a technical assessment of how to keep the assay running and how to verify that answers from one study to another are comparable.