There are a wide range of options for sterility testing out there. What is the most significant advantage EMD Millipore can offer?
The main advantage to working with EMD Millipore is that in addition to a full range of products for both traditional and rapid sterility testing, we also have 40 years of industry, method and regulatory expertise in sterility testing. We offer an array of liquid and agar media, Steritest closed canister systems with different filter options and needle configurations, Steritest pumps for laminar flow hoods or isolators, the Milliflex Rapid system for rapid recovery of microbial contamination, and environmental monitoring media, swabs, and equipment, but it’s our services that really make us different. Application (feasibility and method development), Validation and Calibration/Repair services allow us to support the customer through their entire process life cycle.
If a laboratory or company is new to pharmaceutical products and they will need to work out sterility testing, what key pieces of advice would you offer?
First, be familiar with the regulations. USP <71> recommends membrane filtration as the preferred method for sterility testing and sets a maximum volume for the rinsing step. Next, understand the composition of your product and the product container closure system(s) to determine which type of membrane filter would work best, sample pre-treatment (ie, ointments may require isopropyl myristate, antibiotics may require enzyme inactivation, etc), canister needle configuration, type and volume of rinse fluids, etc. Here at EMD Millipore, we offer method development as an Application service or we can provide guidance to the customer so that they can perform these activities themselves.
What could EMD Millipore offer a laboratory or company that has been in pharmaceutical products business for many years and they have already established long-standing sterility testing methods and protocols?
We find that most customers have ‘inherited’ these test protocols from their predecessors, and there is no documentation for why these procedures were established. Sometimes the methods are no longer compliant with current regulations! Many times these customers are performing direct inoculation (DI); however with the expertise of our Application group, we can perform a filterability evaluation and develop a method to achieve filtration of their product. This enables them to switch from the less sensitive DI method which has a high false negative rate to the more sensitive membrane filtration method. Membrane filtration allows more product volume to be tested and removes any product inhibitory properties by incorporating a rinsing step.
What recent innovations have you seen in sterility testing in the past few years?
The industry has finally made the leap from the traditional 14-day sterility test to alternative, rapid methods with results as quick as 5 days or less. One growth-based rapid method is our ATP bioluminescence technology for detection and enumeration. Another is a simple colorimetric technology that detects changes in carbon dioxide (CO2) levels. A non-growth-based alternative method which has incorporated traditional analytical technology and complex instrumentation includes solid-phase laser scanning cytometry.
When evaluating alternative technologies for rapid sterility, these key factors should be considered: sample volume, direct inoculation vs. membrane filtration, whether or not a pre-enrichment step is required, open vs. closed systems, the number of process steps, destructive vs. non-destructive methods, and the ease of validation.
What do you think the future of sterility testing holds?
The next logical step would be a technology that not only detects low levels of contamination rapidly but also provides a microbial identification of the contaminant at the same time of detection.