The current compendial sterility test has a 14-day incubation time and is often the time-limiting step in the ‘assess and release’ process of pharmaceutical products. There is an ever-increasing number of alternative sterility test systems available that have benefits in addition to faster time-to-result, such as standardization and automation of readouts (eliminating analyst subjectivity) and improved data integrity (e.g., eliminating the need for concurrent verification of results by another analyst). 

Regulators have been encouraging the industry to adopt these innovative systems and, nowadays, there is an increasing number of approvals from various health authorities (including the FDA and EMA) for using an alternative and rapid sterility test for releasing sterile drug product lots. 

This is why BioPhorum’s Alternative and Rapid Microbial Methods team has written an article on Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to their Evaluation, Validation and Global Implementation.

Published in the PDA Journal of Pharmaceutical Science and Technology, the team describes a systematic, nine-step approach for the evaluation, equipment qualification, validation, and deployment of alternative sterility tests. To take advantage of the numerous benefits of alternative sterility tests, the following nine steps are recommended:

1: Identify operational/business need 

2: Define the application 

3: Assess requirements 

4: Compare options and technologies: landscaping and candidate(s) selection 

5: Develop a business case: technical, quality, and business evaluation and justification 

6: Perform proof-of-concept studies/feasibility studies/pre-validation studies 

7: Validate at pilot or primary site 

8: Deploy global/company-wide qualification of additional laboratories 

9: Define regulatory filings and implementation strategy.

Two case studies illustrate possible validation and implementation approaches, including statistical methods. These cover a respiration-based alternative sterility test and an adenosine triphosphate bioluminescence-based alternative sterility test in liquid growth media. 

While most of the steps towards implementation are aligned, the method validation and transfer have been approached differently for each case study because of differences in the chosen technologies and the companies’ internal strategies to validate and roll-out the new method. However, both case studies show a successful implementation of an alternative sterility test for sterile drug products with an ~50% reduced incubation time.

The special feature of the systematic, nine-step approach is that it can be used for many applications. BioPhorum has already used it to create technical papers for Automated Colony Counting Systems and PCR-based Mycoplasma Detection Methods, which follow the nine steps. Now this ubiquitous approach has been successfully used for alternative sterility test systems. The unique value of this paper lies in the insight into how guidelines have been translated into a detailed validation and deployment approach by two companies, as seen in the case studies.

Margit Franz-Riethdorf

Global Change Facilitator, Alternative and Rapid Micro Methods workstream

hello@biophorum.com