Understanding Biological Indicator Grow-Out Times - Pharmaceutical Technology

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Understanding Biological Indicator Grow-Out Times
This study used biological indicators containing   Geobacillus stearothermophilus spores and a new technology to continuously monitor incubated BIs and record nonsterile results.

Pharmaceutical Technology
Volume 34, Issue 1

Analysis of biological indicator incubation grow-out times

The following data were generated to form a basis for the analysis of BI grow-out time following exposure to a moist heat sterilization process; the analysis presented here is based on the results from testing approximately 4,000 BIs. Self-contained BIs (EZ-Test, SGM Biotech) inoculated with approximately 105 Geobacillus stearothermophilus spores were used.

Groups of 100 replicate BIs were exposed to a moist heat sterilization process designed to result in sterilization of only a fraction of the BIs with a target of 30 to 80 of the BIs per group to be nonsterile. For each group of 100 BIs, the average number of surviving spores was calculated by the MPN approach, and the number of BIs with 0,1,2,3,4,5,6,7,8,9, and 10 spores was estimated by a Poisson distribution analysis.

Table II gives the average number of surviving spores per BI and the Poisson distribution analysis for all possible experimental outcomes from 1 to 99 nonsterile BIs.

Materials and methods

A series of experiments were performed using an ISO 18472-compliant resistometer (23). Self-contained BIs produced from four separate Geobacillus stearothermophilus spore crops were tested. The four spore crops, ATCC #7953, were produced over a span of seven years. Fourteen distinct manufacturing lots of BIs were produced from these spore crops; these lots were produced over a span of approximately 18 months. All BI lots and resistance testing results met the requirements of ISO 11138-1:2006,11138-3:2006, and ANSI/AAMI ST79:2006 (4,7,24). For the sterilization exposures, BIs were selected randomly from the 14 production lots.

Groups of BIs were tested in the following manner:

1. Nine groups of 100 and two groups of 50 BIs were tested for sterility with no exposure to the moist heat sterilization process.

2. Ten groups of 100 BIs were exposed to a moist heat sterilization process targeted to result in approximately 300 surviving spores per BI. This number of surviving spores was chosen because it approximates the outcome of a "survival time" exposure as defined in USP 32 (5).

3. Eighteen groups of 100 BIs were exposed to moist heat sterilization processes targeting results of 30 to 80 nonsterile BIs per 100, the "window" in the RIT protocol.

SGM's Smart-Well system (60 + 2 C) was used to incubate the BIs and detect color change in the BI growth medium. When growth was detected, the system recorded the incubation time as hours:minutes; e.g. 2:53. All BIs in these experiments were incubated for a total of seven days.


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