Safety assessment of protein A and derivation of a parenteral health-based exposure limit.

Autor: Graham JC; Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. Electronic address: graham.jessica@gene.com., Anand SS; Boehringer-Ingelheim, 900 Ridgebury Road, Ridgefield, CT, 06877, USA., Bercu J; Gilead Sciences, Inc., 333 Lakeside Dr, Foster City, CA, 94404, USA., Besenhofer L; Abbvie, Inc., 1 N. Waukegan Road, North Chicago, IL, 60064, USA., de Zafra C; Pfizer, 181 Oyster Point Blvd, South San Francisco, CA, 94080, USA., Feng Y; Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, 07065, USA., Fisher C; Takeda Development Center Americas, Inc., 35 Landsdowne St, Cambridge, MA, 02139, USA., Hillegass J; Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, NJ, 08901, USA., Hutchinson R; Johnson & Johnson Innovative Medicine, 1400 McKean Road, Spring House, PA, 19477, USA., Jolly R; Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA., Moudgal C; Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA., Nicholas T; Pfizer, 21717 30th Dr. SE, Bothell, WA, 98021, USA., Olszova D; Gilead Sciences, Inc., 4010 Ocean Ranch Blvd., Oceanside, CA, 92056, USA., Schmitz M; Takeda Development Center Americas, Inc., 35 Landsdowne St, Cambridge, MA, 02139, USA., Semmelmann F; Roche Diagnostics GmbH, Nonnenwald 2, 82377, Penzberg, Germany.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2024 Nov; Vol. 153, pp. 105700. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1016/j.yrtph.2024.105700
Abstrakt: Protein A (PA) is a bacterial cell wall component of Staphylococcus aureus whose function is to bind to Immunoglobulin G (IgG). Given its ability to bind IgG as well as its stability and resistance to harsh acidic and basic cleaning conditions, it is commonly used in the affinity chromotography purification of biotherapeutics. This use can result in levels of PA being present in a drug product and subsequent patient exposure. Interestingly, PA was previously evaluated in clinical trials as well as supporting nonclinical studies, resulting in a database that enables the derivation of a health-based exposure limit (HBEL). Given the widespread use of PA in the pharmaceutical industry, the IQ DruSafe Impurities Safety Working Group (WG) evaluated the available information with the purpose of establishing a harmonized parenteral HBEL for PA. Based on this thorough, collaborative evaluation of nonclinical and clinical data available for PA, a parenteral HBEL of 1.2 μg/kg/dose (60 μg/dose for a 50 kg individual) is expected to be health protective for patients when it is present as an impurity in a biotherapeutic.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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