Dr. Sohrab Habibi Goudarzi – Senior Director of Pharma Discovery and R&D Services, Bryan Parmentier – Senior Principal Scientist of Pharma Method Development, and Yu-Hui (Ann) Fu -Principal Scientist of Pharma Regulatory, along with other scientists at KCAS Bioanalytical & Biomarker Services, coauthored with scientists at Gilead Sciences, Inc. in…

Originally produced by Xtalks on Friday, April 22, 2022 | 12pm EDT (NA) / 5pm BST (UK) / 6pm CEST (EU-Central)  60 min Webinar Description: Due to the relative maturity of the technology, most people’s instinct when thinking about bioanalysis of large molecules is towards ligand binding assays.

Due to the relative maturity of the technology, most people’s instinct when thinking about bioanalysis of large molecules is towards ligand binding assays. However, we urge people to be open to a more flexible approach. Using hybrid LC-MS/MS can be an equally useful tool for quantitation of biological therapeutics and…

Assay validation is required during the development of new drugs or biologics in order to be in compliance with regulatory requirements for all studies that are not considered research/exploratory in nature. Beyond compliance, what is the point of assay validation? Assays must be precise, robust, and specific during use in preclinical studies and clinical trials in order to assure that drug candidates can be accurately evaluated for safety and efficacy. Validation plans assure that an assay will work reliably, even if an assay is run at different sites or by different users. Consider these other elements of assay validation to understand why it is a critical to preclinical and clinical research:   Fit-for-purpose strategy: Each validation plan determines if an assay is made to be fit-for-purpose for a given client’s evaluation needs. Assays can be customized to meet the specific needs of a preclinical screening or clinical trial and fit-for-purpose validation assures that reliable data can be obtained from assay. Test scripts: Test scripts are a series of procedures to be executed during a validation in order to determine if an assay satisfies the necessary specifications or to reveal errors that must be addressed. Running test scripts is essential to the development and continued reliability of a validated assay. GLP compliance: Assay validation must be carried out under the same conditions as will be used for routine assay use. Good laboratory practices (GLP) conditions are needed for many preclinical and clinical applications, and routine quality assurance/quality control monitoring may also be necessary. Be aware of these special circumstances during assay validation. Validation is so much more than a regulatory hurdle. Validation gives you confidence that an assay will yield reliable results that can be trusted to make critical decisions for advancing drug candidates or evaluating clinical efficacy.

Many flow cytometry users are happy to start an experiment with a general protocol and a question about their specimen -- Will my cells make more cytokines or express more markers after activation? Will my cells respond to a novel immunotherapeutic drug candidate?

Have you ever wondered why certain experiments are done under GLP (good laboratory practices) conditions? GLP is a term that is used frequently in preclinical research, and are a set of guidelines that act as a management control for research laboratories and organizations to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemicals (including pharmaceuticals) for non-clinical safety tests[1]. Sometimes it’s hard to understand when and why protocols must be done under GLP conditions. In general, GLP conditions must be maintained when an experimental drug or biologic may be used ultimately in humans and will need to be evaluated by regulators like the FDA.

Immunotherapy research is a rapidly expanding field with a pipeline of monoclonal antibodies in development to treat a range of cancers and autoimmune diseases. The mechanism of action (MOA) used by an antibody to mediate a therapeutic response must be fully defined to enable a candidate antibody to advance down the preclinical development pipeline. It is also required for all antibodies used in clinical research and regulatory IND filings in order to optimize dosing and assess the risk of detrimental side effects.

Drugs and biologics in the research pipeline must undergo stringent preclinical toxicology and safety assessments before use in a clinical trial. Most traditional preclinical toxicology screenings include testing in animal models in order to define toxicological and pharmacological parameters that are critical to determining appropriate dosing such as maximum tolerated dose (MTD).

Flow cytometry has been developed and used as a clinical tool since the invention of the first cytometers in the 1970s. At present, flow cytometry is considered essential for many routine clinical diagnostics, including assays for leukemia and lymphoma, stem cell enumeration, solid organ transplantation, HIV infection status, immunodeficiencies, and hematologic abnormalities. Many scientists involved in clinical trials or drug development are faced with developing clinical flow cytometry assays for multiple phases of clinical development. If you find yourself starting to plan a clinical flow cytometry assay, here are the top 3 issues to think about as you plan your experiment.

Toxicology screening is essential to any preclinical study, and flow cytometry-based toxicology assays are a fast and practical approach. Different animal models are used for toxicology studies, including rodents, dogs and non-human primates. One commonly used technique is the micronucleated erythrocyte endpoint assay, which measures DNA damage induced by exposure to experimental drugs or biologics. This method has been adapted into a validated flow cytometry-based assay and can use erythrocytes from different species. Consider these factors when selecting the best toxicology screening method.

Many basic and clinical immunology studies that focus on T cells include proliferation assays in order to determine if T cells are capable of proliferating under different in vitro or in vivo conditions. Flow cytometry is the ideal approach for measuring T cell proliferation and a suite of staining products…

Many scientists performing preclinical and clinical research hit a point when they need to have an assay validated. You may have painstakingly developed and perfected a particular assay, but now you must put it through the rigors of validation for it to be considered a “validated assay.” The basic principles of assay validation were described in an earlier blog post, but how do you know you if you need an assay validated? Use these questions as a guide to help you figure out your validation situation and get a little less vexed about validation.