Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to Their Evaluation, Validation and Global Implementation

Deutschmann, Sven; Paul, Mousumi; Claassen-Willemse, Marja; Berg, Jonas van den; IJzerman-Boon, Pieta C.; Fonseca, Viviane Grunert da; Brunbech, Ellen; Johnson, Lynn; Knutsen, Chris; Plourde, Lucile; Salvas, Joanny; Villari, Philip; Wysocki, Lisa; Franz-Riethdorf, Margit

doi:10.5731/pdajpst.2021.012672

Cited by 3 publications

(2 citation statements)

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“…19 However, it should be noted that the interpretation of these standards may depend on the nature of the test method. 20 Validation of in-process testing is typically under the control of an individual company's quality management system (QMS) and governed by a quality risk management approach. 21 Risk assessment and risk management plans should be used to determine if a technology is appropriate and can accomplish the goal of quality by design.…”

Section: Need For Rapid Microbial Technologiesmentioning

confidence: 99%

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Integration of rapid bioburden testing into production quality management systems and process control

Ramos,

Najera,

Schaefer

2024

Biotechnology Progress

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The move to integrated continuous bioprocessing (ICB), while providing a means for process intensification, can put added strain on process analytics when conventional methods are used. For instance, traditional microbial methods provide minimal value to ICB processes given that the time required for data to become available is much longer than a typical full cycle of the manufacturing process. Although rapid microbial detection has been in discussion for over 30 years, it is still not routinely deployed in commercial biopharmaceutical manufacturing. One contributing factor is the ability to integrate this technology into a process control strategy and existing quality systems. An understanding of the capability of microbial detection technology available today can be leveraged to implement a control strategy for bioburden monitoring in real time for process intermediates. One key tenet of this proposed control strategy is the use of a “two‐tiered approach” wherein a fast (but possibly less sensitive) test is used to monitor the process and trigger further action for a second, longer duration test which is used to confirm and quantify the presence of bioburden and identify the organism. This approach, presented here alongside several case studies for microbial monitoring, can have broader application for other process analytical technologies where fit for purpose methods could be employed to establish process control alongside real time continuous processes.

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Section: Need For Rapid Microbial Technologiesmentioning

confidence: 99%

“…Eur 5.1.6 19 . However, it should be noted that the interpretation of these standards may depend on the nature of the test method 20 . Validation of in‐process testing is typically under the control of an individual company's quality management system (QMS) and governed by a quality risk management approach 21 .…”

Section: Need For Rapid Microbial Technologiesmentioning

confidence: 99%

Integration of rapid bioburden testing into production quality management systems and process control

Ramos,

Najera,

Schaefer

2024

Biotechnology Progress

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Identification of infectious viruses for risk‐based virus testing of CHO unprocessed bulk using next‐generation sequencing

Hsu,

Talley,

Yang

et al. 2024

Biotechnology Progress

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It is important to increase manufacturing speed to make medicines more widely available. One bottleneck for CHO‐based drug substance release is the in vitro viral (IVV) cell‐based assay on unprocessed bulk. To increase process speed, we evaluate the suitability of replacing the IVV cell‐based assay with next‐generation sequencing (NGS). First, we outline how NGS is currently used in the pharmaceutical industry, and how it may apply to CHO virus testing. Second, we examine CHO virus contamination history. Since prior virus contaminants can replicate in the production bioreactor, we perform a literature search and classify 159 viruses as high, medium, low, or unknown risk based on their ability to infect CHO cells. Overall, the risk of virus contamination during the CHO manufacturing process is low. Only six viruses were reported to have contaminated CHO bioprocesses over the past several decades, and were primarily caused by fetal bovine serum or cell culture components. These virus contamination events can be mitigated through limitation and control of raw materials, combined with virus testing and virus clearance technologies. The list of CHO infectious viruses provides a starting framework for virus safety risk assessment and NGS development. Furthermore, ICH Q5A (R2) includes NGS as a molecular method for adventitious agent testing, paving a path forward for modernizing CHO virus testing.

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Microbiology methods

Jain,

Sharma,

Ventura

et al. 2025

Specification of Drug Substances and Products

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Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to Their Evaluation, Validation and Global Implementation

Cited by 3 publications

References 0 publications

Integration of rapid bioburden testing into production quality management systems and process control

Integration of rapid bioburden testing into production quality management systems and process control

Identification of infectious viruses for risk‐based virus testing of CHO unprocessed bulk using next‐generation sequencing

Microbiology methods

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