Publication of Interest: Neutralizing Antibody Validation Testing and Reporting Harmonization

Experts from the AAPS's Therapeutic Product Immunogenicity Community and the Food and Drug Administration (FDA) recently published an open access article on "Neutralizing Antibody Validation Testing and Reporting Harmonization" in the AAPS Journal. This industry-Agency collaboration helps align the science and data needed for regulatory review of immunogenicity data.

 

The Abstract notes the areas required to be tested during validation and included in the validation reports:

(1) format selection;

(2) cut point;

(3) assay acceptance criteria;

(4) control precision;

(5) sensitivity including positive control selection and performance tracking;

(6) negative control selection;

(7) selectivity/specificity including matrix interference, hemolysis, lipemia, bilirubin, concomitant medications, and structurally similar analytes;

(8) drug tolerance;

(9) target tolerance;

(10) sample stability; and

(11) assay robustness

 

Kudos to Heather Myler and the team for the in-depth consideration of the issues related to NAb assays and in developing recommendations for standardized reporting formats.

AAPS PharmSci 360 Conference Program is Available (22-25 October in Orlando)

The AAPS PharmSci 360 Conference Program has been posted.  The conference will be held in the Orange County Convention Center, Orlando, Florida from 22-25 October.   You can register and book your hotel here.

If you're not familiar with PharmSci360, it is a conference that offers scientific presentations and posters across all fields of drug development along with career development sessions and a solution center with extensive vendors.

Pick any of the 5 Science Tracks (Discovery and Basic Research, Bioanalytics, Preclinical and Translational Science, Formulation and Delivery, Manufacturing & Analytical Characterization) or mix and match presentations to focus on the development of specific modalities.

Join me and your peers to discuss the latest science and network with others from around the globe.

AAPS Webinar: Development and Regulatory Landscape of Cell-based and CAR-T Therapies

 Tuesday May 9, 2023 @ 12:30 PM EDT

Register here.

Description

The webinar on CAR-T and cell-based therapies will touch on emerging concepts in the R&D, manufacturing and regulatory landscape of these immunotherapies. As living drugs, CAR-T and other cell-based therapies present particular challenges in terms of development and clinical and commercial deployment. Despite multiple FDA approvals, challenges in global access, manufacturing and targeting complex diseases such as solid tumors remains challenging. This webinar will present a history of CAR-T therapy and outline recent and emerging innovations of these therapies in terms of disease targeting, CAR design and architecture, and manufacturing advancements.

 

Speaker:

Sandro Matosevic, Ph.D.

Dr. Sandro Matosevic is an assistant professor in the College of Pharmacy at Purdue University, and is a member of the Purdue Center for Cancer Research. Dr. Matosevic runs an NIH-funded research program focused on the development and use of cell-based therapies with natural killer cells and CAR-engineered immune cells in the treatment of cancer and holds a number of patents on the engineering and utilization of NK cells and stem cell-derived NK cells in cancer immunotherapy.

Dr. Matosevic is on the editorial board of several journals, acts on pharmaceutical advisory boards, and has been on committees for several organizations advancing the development and standardization of cell-based therapies, and is current chair of the BIO Focus group of the National Institute for Pharmaceutical Technology and Education. Dr. Matosevic obtained his graduate degree from University College London and completed his postdoctoral training at the Scripps Research Institute.

Publication: A Novel Neutralization Antibody Assay Method to Overcome Drug Interference with Better Compatibility with Acid‑Sensitive Neutralizing Antibodies

A group at Merck recently published the above titled article in the AAPS Journal (2023) 25:18
https://doi.org/10.1208/s12248-023-00783-9 (link). They propose a new approach for the isolation and measurement of neutralizing antibodies that minimizes the harsher acid treatments of BEAD assays.  It appears to build on the PandA assay concept. The initial step is the addition of excess drug to form NAb-drug complexes that are precipitated out of the sample for further processing. After a lactic acid dissociation, biotin-bound-drug is added to be in excess of the expected NAb concentration.  The biotin-bound-drug then complexes with the NAb and is captured on the MSD plate along with the non-complexed biotin-bound-drug.  Using a rhuthenium-tagged drug target, the non-complexed biotin-bound-drug is measured. That measure is the inverse of the complexed (non-complexed biotin-bound-drug-Nab) concentration. 

It is interesting in that it may detect acid-labile NAb that may have been destroyed by the use of a BEAD process. The reduction in the use of biotin-bound-drug is also an advantage.

I look forward to seeing how other labs test this approach and provide further insights on its broad applicability.   What do you think about the proposed assay approach?