INTRODUCTION
This chapter is intended to be used as a risk-based test for the detection of microbial contamination in clear aqueous solutions. Clear aqueous solutions are products for which water is used as the main matrix, which are filterable and have a low level of inherent fluorescent background, e.g., water, ophthalmic solutions, saline solutions, etc.
In solid phase cytometry (SPC), the sample is filtered through a membrane and large volumes of filterable products can be processed. Using fluorescence techniques, the membrane is scanned to detect and enumerate fluorescing cells.
Limitations of this technology may include interfering autofluorescent particles, systems that do not allow microbial identification, and the ability to only test filterable samples. If a manual reading is performed, SPC systems should preferably include the possibility to capture images of the fluorescent events and utilize enhanced imaging systems to ease interpretation. For systems using algorithms for the image and/or signal analysis, the stakeholder must be able to demonstrate that the system can detect microorganisms in the product matrices.
PRIMARY VALIDATION
A primary validation of the method must be conducted by the vendor of the technology or by the end user. If the primary validation has been executed by the vendor, it is the end-user’s responsibility to evaluate whether the validation criteria meet the requirements for the specified application or intended use.
For systems that are using algorithms to enumerate microorganisms, the associated software and/or computer system must be validated.
The primary validation should demonstrate detection of low levels of live microorganisms in product matrices. The following validation criteria are typically applied as noted in Validation of Alternative Microbiological Methods 〈1223〉 for a qualitative presence or absence test: specificity, limit of detection, robustness, repeatability, and ruggedness.
METHOD SUITABILITY TESTING
The microorganisms used for method suitability should include the test strains listed in Table 1 and a selection of test strains relevant to the product and/or manufacturing process supported by a suitable justification. Inclusion of local isolates may be included if relevant for the process or product risk. Use of appropriate culture collection strains that are comparable to in-house isolates is acceptable.
The SPC method must demonstrate detection of the test microorganisms in the product inoculated at NMT 10 colony-forming units (cfu) per test. The inoculum control results for each microorganism should be reported to demonstrate a level of NMT 10 cfu. Considering the variability of the microbial inoculum and assuming it follows a Poisson distribution, it is possible that a low sample size targeting NMT 10 cfu may have an inoculum control that exceeds 10 cfu. A scientific justification would be required if the inoculum control final mean value exceeds 10 cfu and is maintained for the suitability test results.
For direct detection, the count of fluorescent microbial cells in the product sample must not differ by a factor greater than 2 (50%–200%) from the count of fluorescent microbial cells in the sample control without product.
Source from USP and Please refer to USP for details:
https://online.uspnf.com/uspnf/document/2_GUID-8543EC02-CEC9-4299-A0E2-79DB20280EDF_10201_en-US?
Polymer Vial for cell and gene therapies
RTU(ready to use) 2ml COP vial
Copyright © Shijiazhuang Xinfuda Medical Packaging Co., Ltd. All Rights
MAKE AN ENQUIRY
