Biological Indicator Reduced Incubation Time (RIT) Presented by: Andrew Melloy

Transcription

1 Biological Indicator Reduced Incubation Time (RIT) Presented by: Andrew Melloy

2 BIOLOGICAL INDICATOR A device containing calibrated bacterial spores used to monitor the adequacy of sterilization processes Geobacillus stearothermophilus Bacillus atrophaeus

3 REDUCED INCUBATION TIME (RIT) 7 day Incubation 48-hour RIT 24-hour RIT 10-hour RIT

4 REDUCED INCUBATION TIME (RIT) Biological indicator results are not immediate, they require time for incubation of the viable microorganisms so we can determine if they have survived the process

5 REDUCED INCUBATION TIME (RIT) For how long do these samples need to be incubated? ISO days for established sterilization processes (such as moist heat and ethylene oxide) 14-day for novel sterilization methods

6 REDUCED INCUBATION TIME (RIT) The concept of reduced incubation time is to determine a minimum amount of time necessary to achieve valid results These RITs are developed using a guidance set forth by the FDA s Center for Device and Radiological Health (CDRH) in The document Guidance for Industry and FDA Staff - Biological Indicator (BI) Premarket Notification 510(k) Submissions establishes a test protocol for qualifying reduced incubation times

7 REDUCED INCUBATION TIME The US FDA protocol is the only recognized protocol to reduce the incubation time for culturing BIs Assay is required for BI manufacturers who want to reduce the incubation time label claim to < 7 days While the CDRH guidance is directed toward biological indicators used in Healthcare facilities historically it has generally been adopted by the manufacturing industry as well.

8 REDUCED INCUBATION TIME Assay determines the appropriate amount of time needed to recover low numbers of injured spores

9 REQUIREMENTS OF THE FDA RIT TEST PROTOCOL The guidance requires BI manufacturers to expose a total of 100 BIs to partial conditions in the appropriate sterilization process that produce a mixture of BIs that are positive and negative for growth The guidance requires that the overall number of positive BIs from each lot be within the range of 30-80% of the total number of BI s

10 REQUIREMENTS OF THE FDA RIT TEST PROTOCOL The RIT is the time where 97% of the growthpositive results are observed compared to the 7 day total value The protocol must be reproduced with 3 lots of BIs ( 3 x 100 units)

11 REQUIREMENTS OF THE FDA RIT TEST PROTOCOL Those BIs are graded daily and at the end of the seven (7) day incubation period. The daily results are compared against the final result at seven (7) days Using the number of BIs that test positive on day 7 as the base of 100% grow out, the greatest number of days of incubation time to obtain more than 97% positive BIs (based on the 7-day incubation time) in any one of the three lots is the minimum incubation time for the BI

12 RIT QUALIFICATION TESTING

13 REDUCED INCUBATION TIME The US FDA RIT test protocol is NOT globally accepted Currently there is no universal RIT standard

14 REDUCED INCUBATION TIME The more spores present on the BI, the faster the growth-positive result will be detected

15 POSITIVE CONTROLS (10 5 SPORES/BI) INCUBATION TIME # of Positive Units Positive Controls (10 5 ) Time (Hours)

16 SUB-LETHAL EXPOSED UNITS BETWEEN 10 4 AND 10 2 SPORES/BI # of Positive Units Positive Controls Sublethal Exposure (10 5 ) ( ) Time (Hours)

17 SUB-LETHAL EXPOSED UNITS BETWEEN 10 1 AND 10 0 SPORES/BI # of Positives Units Positive Controls Sublethal Exposure 1-10 Spores (10 5 ) ( ) ( ) Time (Hours)

18 QUANTAL ZONE (FDA RIT PROTOCOL) BETWEEN 30 TO 80 POSITIVE BIS PER 100 TESTED # of Positive Units Positive Controls Sublethal Exposure 1-10 Spores (10 5 ) ( ) ( ) 30-80% (+) FDA RIT Protocol Time (Hours)

19 REDUCED INCUBATION TIME Delayed grow-out is the result of a BI with only ONE viable but damaged spore a HIGHLY improbable event in a production sterilizer

20 TIME TO POSITIVE INCUBATION TEST Geobacillus stearothermophilus Time To Positive Incubation Test Positive Controls 3:12 Mean Time to Positive in White Sublethal Exposure 3: Spores 5:16 RIT 6: Time (hours)

21 REDUCED INCUBATION TIME CDER (Centre for Drug Evaluation and Research) is indicating that manufacturers of sterile drug products should adhere to the 7-day recommendation that appears in ISO : Sterilization of healthcare products Biological indicators-part 1: General Requirements states the following in sections and 7.3.2: The incubation time and temperature shall be validated BI manufacturer shall provide instructions for incubation

22 REDUCED INCUBATION TIME FDA CDER (Center for Drug Evaluation and Research) might not necessarily endorse or condone the test protocol published by the FDA CDRH; citing that the test parameters set forth in the CDRH protocol are applicable for BIs used to monitor sterilization processes in healthcare facilities, but are not appropriate for BIs that are used in a manufacturing setting. CDER does not generally recognize the acceptance criterion that the minimum incubation time is the greatest number of days to obtain more than 97% positive BIs subjected to a partial cycle.

23 REDUCED INCUBATION TIME ISO 14161: Sterilization of healthcare products biological indicators-guidance for selection, use and interpretation of results section acknowledges that a BI manufacturer may validate a reduced incubation time that does not have to be repeated by the end user as long as the end user uses the BI in the same sterilizing agent for which the BI was designed and validated

24 REDUCED INCUBATION TIME BI users in the Pharmaceutical/manufacturing industry would be prudent to disregard that which appears in ANSI/AAMI/ISO 14161, section and incubate their exposed BIs for a full seven days BI users in the pharmaceutical/manufacturing industry might choose to incubate and score the BIs at the reduced incubation time that appears in the instructions and keep the BIs incubating for the remainder of the 7-day period at which time the BIs are again scored for results.

25 ISO TC 198 WG 4 MINIMUM INCUBATION TIME - MIT Understanding BI Grow Out Times, Part I (January 2010): Biological-Indicator-Grow-Out-Times/ArticleStandard/Article/detail/ Understanding BI Grow Out Times, Part II (June 2013): Indicator-Grow-Out-Timesm/ArticleStandard/Article/detail/ Historical Perspective (May 2012): Indicator-Growout-Times-The-Impact-on-E/ArticleStandard/Article/detail/ Establishing a Minimum Incubation Time for Biological Indicators, Part III (Dec 2013): Minimum-Incubation-Time-for-Biologi/ArticleStandard/Article/detail/830014

26 ANTICIPATED RESULTS Present to ISO a database statistically analyzed protocol that focuses on the expected levels of contamination not the last survivor Reduce the required incubation time for BIs to less than occurs with the FDA protocol so their results are timely Direct thinking to focus on the first positive not the last positive

27 ANTICIPATED RESULTS Enhance the perception that the BIs are an essential tool that should be used more diligently Provide regulatory agencies and notified bodies with a globally harmonized standard

28 IN CONCLUSION Reduced Incubation time means faster results and potential release of product however you must take into account your regulatory environment ISO is currently working on Minimum Incubation Time (MIT) standards as a replacement for the current RIT

29 ANY FURTHER QUESTIONS? Thank You!