Bindra, Dilbir, Bluemel, Markus, Kearns, Katrina, van Montfort, Bart, Newman, Alice and Yang, Houjun (2025) Patient-Centric Endotoxin Acceptance Criteria. Bioprocess International, 2025 (2-SEP).

Abstract

Summary:
This document discusses the industry's opinion on endotoxin acceptance criteria for parenteral drug products, emphasizing the need for patient-centric criteria based on average body weight and the threshold pyrogenic dose of 5 EU/kg/hr. It highlights the inconsistency between regulatory expectations and compendial guidelines, including recent trends to tighten acceptance criteria using the lowest body weight or safety factors. The document argues that overly strict criteria can risk supply consistency and limit future process improvements. It recommends calculating endotoxin contributions from diluent and co-administered drugs using product-specific calculations or a blanket safety factor. The analysis of historical data from FDA observations, product recalls, and adverse event reports demonstrates that the current industry practices provide significant safety margins. The conclusion is that the use of average body weight for calculating endotoxin acceptance criteria is scientifically justified, ensuring patient safety and manufacturing efficiency.

Item Type:	Article
Keywords:	Endotoxins
Date Deposited:	02 Dec 2025 00:45
Last Modified:	02 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/57186