With increasingly complex pharmaceutical products, biologics, and cell and gene therapies, there is greater demand for more advanced and efficient testing solutions. Sterility testing plays a crucial role in drug product development, ensuring the safety of products by detecting microbial contamination.

A key driver of rapid microbiology testing is increasing pressure from regulatory agencies, such as the FDA and EMA, to ensure high standards of quality control with increasingly stringent guidelines for pharmaceutical product testing. As regulatory requirements change and evolve, there is a growing need for faster and more accurate testing methods.

Rapid sterility testing uses advanced bioluminescence technology to detect microbial adenosine triphosphate (ATP). This method reduces the testing time to at least half the time required by the traditional compendial method.

Rapid testing for product sterility is useful for a broad range of product types, particularly those with limited shelf lives, that require prompt release to market, or that are manufactured in small batches.

Nelson Labs, a provider of microbiological and analytical chemistry testing and advisory services, recently expanded its capabilities by adding product-sterility testing through rapid microbiological methods (RMMs) at three laboratory sites in the U.S. and Europe.

Nina Moreno, Global Segment Director, Sterility Assurance, Nelson Labs, shares insight on rapid sterility testing, the technologies used, advantages, and regulatory considerations.

Contract Pharma: How does rapid sterility testing work, and what technologies are typically used? 

Nina Moreno: There are various options available for rapid sterility testing, including ATP bioluminescence, respiration-based methods, solid-phase cytometry, and nucleic acid-based amplification. Each of these methods has different advantages, so it is important to define the factors that are most critical for your rapid test requirements. This can include parameters such as the limit of detection, the time to result, and the ability to perform organism identification as part of the investigation process. 

Nelson Labs offers an ATP-based rapid sterility test option. ATP bioluminescence has a long history of use in the industry as a reliable means of detecting viable organisms. This method allows for detection times that are faster than those relying on the compendial method, but it still supports the organism-identification process in the event of contamination. This type of ATP-based method can be applied to various products, including pharmaceuticals and medical devices. 

Contract Pharma: What are the main advantages of rapid sterility testing compared to traditional methods?

Nina Moreno: The primary benefit of rapid sterility testing is the ability to significantly reduce the time to result, while maintaining high standards for quality and safety. 

In addition, many rapid sterility tests utilize instrumentation to generate automated results. This eliminates the need for visual examination to detect evidence of growth. Technology-based rapid systems allow for detection of contamination at lower levels and earlier stages in the process than what can be achieved through traditional visual examination. 

Contract Pharma: What is the typical time to result for a rapid sterility test compared to a traditional sterility test?

Nina Moreno: The time to result for a traditional sterility test per USP <71> is 14 days. It can potentially be 18 days if a subculture is required. With a rapid test approach this time can be significantly reduced. For example, an ATP-based detection method for a sterility test can produce results in as little as 6 days. 

Contract Pharma: What are the potential drawbacks or limitations of rapid sterility testing? 

Nina Moreno: Rapid sterility testing requires validation, as outlined in USP <1223>, prior to implementation. It is also important to understand regional regulatory requirements when considering global implementation of a rapid sterility test method. 

Contract Pharma: What are the critical parameters that need to be evaluated during method validation for rapid sterility testing?

Nina Moreno: For a qualitative test such as the sterility test, the required validation parameters include specificity, limit of detection, robustness, repeatability, ruggedness, and equivalency. A method suitability test is also necessary to demonstrate that the test system is acceptable for the product being tested. 

Contract Pharma: What regulatory considerations are there for implementing rapid sterility testing? 

Nina Moreno: The regulatory outlook for rapid sterility test methods is positive; there is an established history of acceptance and use, and those pursuing rapid methods are encouraged to work with regulatory authorities on their approach.

Standards, such as USP <1223> and <1071>, are in place to help guide the implementation of rapid test methods. In addition, new USP chapters <72> and <73> were written specifically for the rapid testing of short-life products using either respiration-based methods or ATP bioluminescence.

Contract Pharma: Is rapid sterility testing suitable for all types of pharma/biopharma products, or are there specific applications where it is particularly beneficial?

Nina Moreno: Rapid sterility testing is suitable for many product types, including pharmaceuticals, cell and gene therapies, and medical devices. However, a rapid test method can be very beneficial for products that have a short shelf life, where the product is administered to the patient prior to the time when a compendial 14-day test can even be completed. 

If you are seeking additional information on whether a rapid sterility test is right for your product, Nelson Labs is available and happy to assist with your needs.