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Validation of Growth Direct Applications: EM and Sterility Testing

Written by Rapid Micro Biosystems | Dec 5, 2013 11:00:00 AM

In a previous post, we discussed the general process for validation of the Growth Direct™ System. No matter the application, Growth Direct™ System users must complete installation and operational qualifications (IOQ), performance qualifications (PQ) and method suitability testing. Overall, these validation processes ensure the system's components are working correctly and the machine's imaging technology is producing reliable results with a given set of contaminants and finished products.

Still, more nuanced testing is often necessary to validate the Growth Direct™ System's specific applications. While bioburden testing doesn't require any additional validations, environmental monitoring and sterility testing do take a few extra steps.

Environmental Monitoring (EM)

While the Growth Direct™ System process for environmental monitoring does involve media defined in the US Pharmacopeia, it requires a membrane – rather than an agar plate – be used to capture organisms from surfaces and air. Manufacturers will therefore need to demonstrate equivalence in colony growth between this membrane and the traditional naked agar. The following steps are necessary during EM validation:

  • Growth Promotion of Media Cassettes: As with any application validation, manufacturers will need to grow colonies on Growth Direct™ System cassettes to demonstrate accuracy, precision, range, specificity and limits of detection.
  • Verification of Disinfectant Inactivation: Since EM takes place in environments cleaned with disinfectants, Growth Direct™ System users will need to verify that those chemicals aren't interfering with colony growth within their cassettes. Disinfectants are spread on coupons, which are then dried and sampled with a contact plate. Test organisms are then added to that contact plate to demonstrate colony growth.
  • Desiccation Effect Verification: Manufacturers requiring air samples will need to verify airflow and resultant desiccation aren't affecting the performance of their growth media. This requires the Growth Direct™ System membranes be run in parallel with the traditional media and these different media ultimately display equivalent levels of growth.
  • Time-to-Result (TTR) Selection: During performance qualification (PQ), users select their TTRs based on a suite of microorganisms commonly found in their clean rooms, environmental isolates and stressed organisms.
  • Parallel Testing: To ensure that commonly found microorganisms are growing within their selected TTRs, manufacturers complete the EM validation process by running new and old methods in parallel. They verify the recovery of organisms on the Growth Direct™ System membrane surfaces, using a variety of test sites to cover wide ranges of criticality and contaminant distribution.

Sterility Testing (ST)

Sterility testing with the Growth Direct™ System involves capturing organisms on membranes as described in the Pharmacopeia, but the growth media is a broth with a different formulation. Also, the membrane is placed on top of this broth, rather than submerged.

There is more than one way to validate the performance of this membrane-broth combination, and the method will depend on whether a manufacturer will be using a qualitative Presence Absence test or a quantitative Enumeration test for sterility. To validate a qualitative testing method, specificity, limits of detection and equivalence are required, and the exact parameters are effectively the same as those found in USP<71>.

Validation of a quantitative sterility test requires all of these components, as well as accuracy, precision, linearity and range. Exact validation procedures vary from one company to the next, but they will typically require sample sizes of microorganisms to be grown in parallel within the new and traditional media.

Still have questions regarding the Growth Direct System? Contact us today.