AAPS PharmSci 360 2026: CMC and NAM Strategies

Vibha Jawa, PhD, chief scientific officer at EpiVax, spoke with PharmTech at AAPS PharmSci 360 in New Orleans, about new approach methodologies (NAMs) and preclinical testing approaches in drug development. There is a gap, says Jawa, between assay development and real-world drug products.

Organoids, microphysiological systems, and other in vitro assays are typically built using only the API or discovery-stage molecule, before it has been formulated or taken through process development. While these models can capture how a specific chemistry or biologic interacts with a target, formulation introduces new critical quality attributes, says Jawa. A molecule may misfold, degrade, aggregate, or form subvisible particles, all of which can add safety liabilities that go undetected if the models never use formulated material. She urges early collaboration with chemistry, manufacturing, and controls teams and process development scientists so models can be validated with representative material, rather than discovering unanticipated liabilities that undermine investigational new drug (IND)-enabling toxicology studies, which use material close to the first-in-human drug product.

Jawa points to the TGN1412 case as an example of the shortcomings of animal studies, in which a severe cytokine storm emerged only in the clinic. The animal species used lacked the relevant receptor biology, and human-relevant assays had not been used to examine the molecule’s interaction with human immune cell receptors. She notes that animal models can be informative when receptors and targets match, explaining immunogenicity and mechanism-driven safety events, but they may still miss other toxicities, such as hypersensitivity reactions driven by preexisting antibodies that humans carry and animals do not.

The FDA’s draft guidance on NAMs rests on context of use, weight of evidence, and technical characterization, explains Jawa. Although NAMs may not replace animal studies entirely, they can reduce animal use and supplement existing data. She advises sponsors to raise their NAM-based strategy with the FDA at the pre-IND stage to confirm the package is viable and avoid delays to first-in-human studies.

About the Speaker

Vibha Jawa, PhD, chief scientific officer at EpiVax, a bioinformatics company in Providence, Rhode Island, that designs better vaccines and optimizes biologics to reduce immunogenicity risk. Before joining EpiVax, Jawa spent 5 years leading a translational group at Bristol Myers Squibb and earlier worked in translational drug development at Merck and Amgen.