We’re proud to share that Eagle’s experts were recently interviewed by American Pharmaceutical Review magazine for an in-depth discussion on alternative sterility testing methods. The article was published in the September issue of American Pharmaceutical Review.
Below, you can read the full feature and explore insights from our team on evolving sterility testing approaches and future industry trends.
What are some of the key challenges in adopting rapid sterility testing methods over the traditional USP <71> approach within the pharmaceutical industry?
“Traditional” methods are viewed as the gold standard, highly recognized, widely regulated, and backed by decades of acceptance, which leaves little external pressure to move away from them. On the other hand, adopting rapid methods requires significant investment in new technologies, extensive validation to meet regulatory expectations, and overcoming cultural hesitation to abandon a well-established approach. Moreover, as we explore rapid methods more deeply, it becomes clear they are not a one-size-fits-all solution. Each comes with its own strengths and drawbacks, and because they are designed to be faster and more efficient, they often become more selective in their application.
How can method suitability testing help mitigate risks of false results or incompatibilities when switching to faster sterility assays for novel formulations?
Method suitability testing serves as a critical checkpoint to ensure that a sterility test is truly reliable for a given product. Different drug products can have unique properties such as viscosity, color, pH, or antimicrobial activity that may interfere with the sterility test and either mask contamination or generate misleading outcomes. By performing method suitability, laboratories confirm that the test can detect potential contaminants in the presence of the actual product, rather than just in a clean growth medium.
This step is critical when transitioning to newer or faster assays, as it minimizes the risk of false negatives (contamination being missed) or false positives (contamination appearing where none exists). In other words, it ensures that the chosen method is both accurate and compatible with the product’s characteristics, building confidence in the results and supporting regulatory expectations for patient safety.
How do recent updates in USP <797> and USP <1223> affect the validation and acceptance of rapid sterility testing technologies, and what requirements must be met for regulatory compliance?
Recent revisions to USP <797> and USP <1223> clarify how rapid sterility tests can replace the traditional USP <71> sterility test, provided it is proven that the alternative is at least equivalent (non-inferior) and fit for its intended use. In other words, if the rapid method is validated per <1223> and implemented within a compliant quality system per <797>, it can be used it in place of <71>. There must be however, A <1223>-aligned validation that includes IQ/OQ/PQ, accuracy, precision, specificity/selectivity, sensitivity/LOD, robustness, and equivalence/non-inferiority vs. <71>, plus method suitability for each product.
What are the current FDA and USP expectations for alternative rapid sterility methods, and how can organizations demonstrate equivalency or superiority to USP <71>?
FDA does allow rapid and alternative microbiological methods for in-process, and finished-product release, including sterility, if you demonstrate the method is equivalent or better than the conventional method. You would also need to validate accuracy, sensitivity, specificity, and reproducibility per 21 CFR 211. USP <797> states that for sterility testing you may use USP <71> or a validated alternative that is non-inferior to <71>, with validation aligned to USP <1223>, which in turn provides the playbook for selecting, validating, and justifying alternative and rapid methods, emphasizing qualification with the actual product and demonstration of equivalence or superiority to the compendial method.
What are the main differences between rapid sterility testing platforms such as ScanRDI®, BacT/Alert®, and Celsis®, and what advantages does each bring for different product types?
Each has different detection principles, and their strengths depend on the type of product being tested.
ScanRDI® (bioMérieux) uses solid-phase cytometry with fluorescent staining to directly detect individual microbes captured on a membrane. It is non-growth-based and can deliver actionable sterility decisions in ~4 hours. That makes it a strong fit for short filterable aqueous products with a short BUD.
BacT/ALERT® (bioMérieux) is an automated growth system that monitors CO₂ production in inoculated culture bottles via a colorimetric sensor. It is highly versatile across complex matrices, including cell & gene therapy and products where filtration is impractical or organism recovery is challenging. It can yield results in 7 days.
Celsis® (Charles River) employs amplified ATP bioluminescence after enrichment to flag contamination. It can yield sterility results in 6-7 days. It’s a strong option for a wide range of filterable and non-filterable products.
How does the ScanRDI® system achieve 1-2 day sterility results, and what types of pharmaceutical products can it effectively test?
ScanRDI® utilizes solid-phase cytometry principles to detect viable microorganisms. Unlike traditional methods, it is not growth-based, allowing for rapid detection. The process begins by filtering an appropriate volume of the product through a 0.45 µm membrane. The membrane is then rinsed to eliminate any residual substances that could cause autofluorescence. Viable cells retained on the membrane are stained using proprietary reagents and incubated. These reagents interact specifically with enzymes present in viable cells. This enzymatic activity transforms one of the reagents into a fluorescent compound, causing the viable cells to fluoresce. The prepared membrane is placed into the ScanRDI® instrument, which performs a laser scan across the entire surface. The software flags all fluorescent events—these may include viable cells or autofluorescent particles—and records their X-Y coordinates.
Finally, the operator reviews these coordinates under a fluorescence microscope to distinguish true viable cells from background particles or artifacts.
What new advancements or future trends are emerging in the field of rapid sterility testing, and how might they further shorten turnaround times or expand testing capabilities for complex biopharmaceutical products?
New advancements in rapid sterility testing are focused on reducing turnaround times from weeks to hours or days by leveraging technologies like nucleic acid amplification, bioluminescence and nanopore sequencing. These innovations help accommodate the limited shelf-life of complex biopharmaceuticals, such as cell and gene therapies in addition to conventional sterile pharmaceutical products. Future trends include greater automation, machine learning for faster analysis, and new technologies for in-process and real-time monitoring.
