Use of Generic PK Assays to Support Toxicology Studies for NBE

Christine Bain, Ph.D. February 7, 2025

What is a generic PK assay?

A generic pharmacokinetic (PK) assay, also referred to as a universal PK assay for New Biologic Entities (NBE), is used to measure circulating human biotherapeutics—primarily antibody-based—post-administration across various non-human matrices. These assays are particularly beneficial when drug-specific reagents, such as anti-idiotype antibodies, are unavailable, which often happens in early stages of drug development or with novel antibody formats.

What sets these assays apart is their flexibility. Instead of relying on a specific antibody or reagent tailored to one drug, a generic PK assay can be adapted to measure multiple drug candidates, making them a valuable tool for preclinical evaluation. They provide critical data for:

Ranking multiple drug candidates: Identifying the most promising candidates for further development.
Determining systemic drug levels in animals: Measuring how the drug distributes and persists in the organism.
Adjusting dose ranges for GLP toxicology studies: Ensuring the correct dose range is chosen for safety and efficacy testing.

One Size Does Not Fit All

When selecting a Ligand-Binding Assay (LBA) method for generic PK, several factors need to be considered to ensure the method’s suitability for the candidate drug^1,2. Key considerations include:

Characteristics of the drug: Factors such as the antibody scaffold, isotype, and specific engineering features (e.g., humanization or glycoengineering) play a significant role in method selection.
The antibody format: Whether the drug is a monoclonal antibody (mAb), a multi-specific antibody, or an antibody-drug conjugate (ADC), each format has its unique considerations.
Reagents: The choice of capture and detection reagents can vary based on the antibody target, anti-species antibody targeting the light chain or Fc fragment, or specific isotypes that are commercially available.
Cross-reactivity considerations: When measuring humanized antibodies in non-human primates (NHPs), care must be taken to address any potential cross-reactivity that could affect the assay’s sensitivity and specificity.

Additionally, the technological platform used for generic PK assays must be chosen based on factors like expected dynamic range, sensitivity, sample volume, and matrix interference. This ensures that the assay delivers accurate and reproducible results across the intended testing conditions.

“Off-the-Shelf” Does Not Mean “Ready-to-Use”

While “off-the-shelf” generic PK assays may seem like a convenient option, it’s important to note that they still require thoughtful adaptation for each specific application. These assays might need a few days of method development to fine-tune parameters like working range, sensitivity, and matrix effect before they’re ready for use in non-clinical sample analysis.

Scenarios for the use of generic PK assays

To better understand how generic PK assays are applied in practice, explore in the document below two examples that illustrate their flexibility and adaptability in real-world drug development scenarios for the Selection of a Lead Monoclonal Antibody and Dose Range Finding for a Monoclonal Antibody.

CaseStudy_GenericPK_KCASBio Download

Conclusion: Accelerating Preclinical Drug Development with Generic PK Assays

At KCAS Bio, we have extensive experience in developing and troubleshooting LBA-based generic PK methods. The versatility and flexibility of these assays are invaluable in the early stages of drug development, as they enable rapid, cost-effective data generation. By streamlining the preclinical process, generic PK assays accelerate the transition to late GLP toxicology studies and ultimately to the First-In-Human clinical phase.

Generic PK assays are more than just a convenience—they are a powerful tool that allows pharmaceutical and biotech companies to make faster, more informed decisions, ultimately bringing life-saving therapies to patients more efficiently.

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