FDA Issues Guidance on Therapeutic Protein Immunogenicity Tests

The FDA released guidance for sponsors of therapeutic proteins on developing tests to assess immunogenicity during clinical trials.

The recommendations apply to assays that detect one or more anti-drug antibodies (ADAs) and may also apply, on a case-by-case basis, to certain peptides, oligonucleotides and combination products, the agency said.

Sponsors should use a risk-based approach to evaluate and manage immune responses and immunologically-related adverse events for therapeutic protein products that affect their safety, efficacy, pharmacodynamics and pharmacokinetics, the agency said.

The guidance recommends several testing strategies. For example, it suggests that sponsors use a multi-tiered ADA testing approach, using a sensitive screening assay to detect small levels of low- and high-affinity ADAs. Samples that test positive in the screening assay should be put through a confirmatory assay to show ADAs are specific to the therapeutic protein product.

In some situations, sponsors should develop assays to differentiate between antibody isotypes. For example, results from antigen-specific IgE assays may be informative for therapeutic protein products with a high risk of anaphylaxis or for which anaphylaxis has been observed, the agency said.

“Immunogenicity tests should be designed to detect ADA that could mediate unwanted biological or physiological consequences such as neutralizing activity or hypersensitivity responses,” the agency said.

Read the full guidance here: www.fdanews.com/01-23-19-ImmunogenicityTesting.pdf. — James Miessler