How Advanced PK/TK Protocols Strengthen Data Integrity

*Full transcript available below

Sara Underwood, senior pharmacokineticist at Alturas Analytics, offers valuable guidance for pharmacokinetic (PK) and toxicokinetic (TK) study design and regulatory compliance in an interview with BioPharm International® at American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, held in San Antonio, Texas, on Nov. 9–12, 2025.

In bio/pharmaceutical product pipelines, the reliability of PK/TK data not only streamlines drug development but forms the backbone of regulatory strategy. Underwood emphasizes that robust PK/TK protocols are vital, saying, “You really need quality samples in order to have faith in the results that you can then put into your pharmacokinetic parameter evaluation for non-clinical studies.” She highlights how precise control over sample integrity, analytical variability, and biological variables can directly influence a program’s success.

From study conception, bio/pharma stakeholders must address pre-analytical variables—such as standardized animal handling and dietary controls—and select validated bioanalytical methods to minimize technical inconsistencies, Underwood explains. These disciplined approaches help manufacturers avoid batch failures and costly repeats, ultimately accelerating timelines and supporting smoother investigational new drug submissions, she notes.

How can CRO partnerships elevate bio/pharma manufacturing and drug development success?

Underwood also emphasizes that partnership models can be a differentiator for today’s leading drug developers. “Your CRO [contract research organization] becomes your source of regulatory intelligence,” she says, drawing attention to the value of strategic collaborations that extend beyond transactional services to function as regulatory knowledge hubs. She adds that these relationships enable rapid adaptation to changing compliance landscapes, facilitate rigorous audit trails, and support data packages assembled in alignment with good laboratory practice and good clinical practice requirements.

Underwood also states that actionable best practices ensure that manufacturers and drug developers not only boost PK/TK study reliability but also align their workflow with evolving industry and regulatory standards. The result, she notes, is a more nimble, compliance-ready organization with reduced development risk and enhanced speed-to-market for new therapies.

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Transcript

Editor's note: This transcript is a direct, unedited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

My name is Sarah Underwood. I work for alturas analytics. I'm the Senior pharmacokineticist there, and I have 27 years in the biotech industry, with the last 11 being specifically at alturis. So that was my first CRO job, and I am responsible for the PK department and doing NCA analysis and all the reporting, and I'm also a volunteer on the C disk send team.

It's the study design that should be optimized so that you're setting the stage to have sufficient quantifiable drug concentrations to evaluate the necessary PK parameters to meet the study objectives. So precision of pharmacokinetic parameters isn't quite the same as you would think of precision in a bioanalytical method. It's a bit more nuanced, because it depends on the integrity of your samples, and it's kind of like the proverbial garbage in does not equal Gospel out. So you really need quality samples in order to have faith in the results that you can then put into your pharmacokinetic parameter evaluation

for non clinical studies. Specifically, you need to know what decisions the data is going to support. So ensure that you have really clear objectives, a solid understanding of the regulatory expectations, and know what are you going to do if the results aren't what you expect?

The Big Three are pre analytical, analytical and biological variability, and your study protocol should take care of the pre analytical variability by defining the overarching conduct of the study, such as fed versus fasted, how the animals are going to be trained for procedural stress and method handling of your samples that should all be described in your protocol, having a validated bioanalytical method will help mitigate that analytical variability, or at least prepare you for what the expected variability will be. Biological variability can be mitigated by using inbred strains of animals and using aged, matched animals as well, and having an understanding of the different species and strains physiology and how your anticipated molecule will behave in that species,

a strategic relationship With a CRO is essential in achieving regulatory readiness in PK studies, because it is it functions as an integrated partnership, not just here's an extra set of hands, so your CRO becomes your source of regulatory intelligence. In that matter, with strict adherence to GLP and GCP and validated Bioanalysis that they already have stood up. They've had it stand up to regulatory scrutiny already across multiple audits, so they also know how to present the data and write justifications in the precise language that regulatory regulators are expecting.

First and foremost study designs should be made under the guidance of the ich m3 and regulations described in 21 CFR 312, which is for ind applications. So a robust pktk protocol should have clear objectives again, and the primary objective to describe the systemic exposure in animals and its relationship to the dose over time, over the entire time course of the study. Secondly, the objective should be again to bridge that nonclinical data to the clinical plan. The early phase studies should also contribute to the design of the subsequent studies that support the choice of the species and treatment regimen you.