Improved Time-to-Detection of Slow-Growers Microorganisms with an Automated Growth-Based Method

Introduction

Automated Growth-based methods are used for rapid detection of microbial contamination in pharmaceutical products. Historically, regulators have classified such methods as “alternative” to the compendial U. S. Pharmacopoeia (USP) chapter <71> / European Pharmacopoeia (EP) chapter 2.6.1 (1, 2), requiring extensive validation prior to implementation. In recent years, the regulatory environment has been evolving to be more inclusive of rapid and alternative methods for designated products thanks to chapters such as the EP 2.6.27, USP draft <72> and USP <1071> (3-5).

EP 2.6.27 and USP <72> (3, 4) specifically support the use of technology of the BACT/ALERT® 3D DUAL-T (BTA) solution as “compendial” with some restrictions. For short shelf-life products such as Cell And Gene Therapies (CAGT), every hour gained on release testing is crucial to quickly deliver therapies to patients in need. The BACT/ALERT® 3D DUAL-T answers this need by providing automated, non-destructive, growth-based detection of most relevant microorganisms in less than 72 hours. Despite this, the current practice is to release the product after 7 days of incubation, due to the risk of contamination with “slow grower” microorganisms such as molds or Cutibacterium acnes. To improve the detection of such microorganisms, different culture media, growth factors, and incubation conditions were evaluated.

The objective of this document is to showcase data on the optimization of BTA incubation conditions can lead to notable improvements in time-to-detection.