By Paul Nirgenau and updated by Mesa staff
The Contract Studies team at Mesa Labs provides a variety of services to support companies that produce sterile products. These services range from third-party label claim verification on lethality indicators (biological and chemical indicators) to product D-value studies on medical devices and pharmaceutical products.
Mesa Labs possesses the necessary equipment and supplies for conducting these tests, the most important of which are resistometers and calibrated bacterial spores. Resistometers are specialized pieces of equipment designed specifically for the performance evaluation of biological and chemical indicators. The bacterial spores required for product D-value studies are inventoried at Mesa Labs or can be produced upon demand (in the case of bioburden studies).
Most of the services provided are a precursor to a sterilization validation event or to verify the performance of a lethality indicator tool prior to its use in a production setting.
Third-party testing of biological indicators is a common practice when a quality audit of the vendor has not been conducted and therefore confidence in the vendor has not been established. D-value studies on product and/or families of product are a component of a sterilization development process. Not only is this a sound scientific activity but it is also expected from a regulatory standpoint.
The Contract Studies group at Mesa Labs was formed in 1998 in response to pharmaceutical companies requesting product D-value studies. As such the Mesa team has many years of experience testing a wide range of products and has expanded its offerings to include other services related to the field of sterilization. Arguably, no other lab has more experience in conducting product D-value studies than the Contract Studies group at Mesa Labs.
D-value Analysis on Liquid Pharmaceutical Products
Mesa Labs performs steam D- and z-value analysis on pharmaceutical products using Geobacillus stearothermophilus, or Bacillus subtilis “5230” spores for heat-sensitive products. Onionskin glass ampoules containing the pharma product and 106 spores are manufactured and exposed to gradient cycles in a steam resistometer. Four ampoules per cycle are exposed, and population assays are performed immediately after exposure. The D-value for liquid pharmaceutical products is calculated using the Survivor Curve Method.
The low volume of product, use of onionskin glass ampoules, and square wave steam cycle of the resistometer generate data that can be used for multiple volume configurations if the time to temperature is known for each volume. If this information is not known, D-value analysis can also be performed with direct inoculation into the customer’s product configuration. Mesa Labs is licensed with the Drug Enforcement Agency and can perform studies on controlled substances.
D-value Analysis on Pharmaceutical Stopper/Piston/Vial Components
Inoculating the septum or most difficult location of the component to sterilize, D-value analysis is performed using the fraction/negative method with 10 or 20 components per cycle. Components are exposed to gradient cycles in a resistometer, aseptically cultured, and monitored for growth. D-values are calculated using either the Limited Holcomb-Spearman-Karber or Stumbo- Murphy-Cochran method.
D-value Analysis on Custom Biological Indicators
Mesa Labs can perform resistance testing on custom biological indicators. Analysis can be performed using the customer’s specified inoculation location, or Mesa can determine the most resistant inoculation location. In the past, we have performed resistance testing on syringes, powders, membranes, medical devices, lumens, and Process Control Devices.
Bioburden Resistance Testing
Spore-forming bacteria that have been identified by the customer can be sent to Mesa Labs on a plate or slant. The bacteria will be grown (targeting a 108 population), harvested, and inoculated into WFI (Water for Injection) or product ampoules. D-value analysis is conducted using the Survivor Curve Method.
Verification of D-value, Survival/Kill time, population, purity, and microbial identification listed on the Certificate of Analysis can be performed on other manufacturers’, as well as Mesa’s, biological indicators. The Contract Studies Lab is ISO 13485 certified for these services and functions as an independent lab because its reporting authority is separate from Mesa’s biological indicator manufacturing.
We can work with you to design a study around your product and sterilization method. The Contract Studies team at Mesa can perform testing in steam, ethylene oxide, dry heat, and vaporized hydrogen peroxide processes.