Schlereth, Katharina, Kiesel, Harald, Thoelken, Sebastian, Birmes, Lukas, Oberhuber, Christina, Knappe, Diana, Arakel, Eric, Roeck-Nieder, Maria, Koelbert, Celine, Isken, Jennifer and Le, Yen Thi (2025) Setting the Standard Cleanliness Grades Behind Every Sterility Test Isolator. PDA Letter.

Abstract

Sterility testing is a critical quality control measure in pharmaceutical manufacturing, ensuring the absence of viable microorganisms in sterile products. Traditionally performed in grade A laminar airflow cabinets within grade B cleanrooms, the industry is transitioning toward isolator-based systems that offer superior contamination control. This shift has prompted debate over the required environmental classification for the background in which sterility test isolators are located.
This paper explores the regulatory landscape surrounding this issue, highlighting the lack of harmonized guidance. While pharmacopoeial chapters emphasize aseptic conditions and environmental monitoring, they do not mandate specific background classifications. Regulatory documents vary in specificity, with some dismissing the need for classified environments, while manufacturing guidelines like EU GMP Annex 1 prescribe grade D for closed isolators and grade C for open ones.
The distinction between sterility testing and aseptic manufacturing is crucial. Sterility testing, a quality control activity, poses minimal direct risk to patient safety compared to manufacturing failures. However, aligning sterility testing environments with manufacturing standards can facilitate root cause investigations and regulatory discussions.
Ultimately, the requirement for a grade D background is not universally mandatory but should be justified through risk assessment and contamination control strategy (CCS). Cleanliness of the isolator, test samples, and consumables is paramount, and environmental monitoring alone does not prevent false positives. The paper advocates for a balanced approach, recognizing both regulatory flexibility and the importance of robust contamination control practices.

Item Type:	Article
Date Deposited:	26 Dec 2025 00:45
Last Modified:	26 Dec 2025 00:45
URI:	https://oak.novartis.com/id/eprint/58658