Info for: Home | Site Map | Archives | About Us

Medical Device School

Safety and Efficacy First

Medical Supplies
 

 

Medical Devices

FEATURED PRODUCT:  Interpretation of FDA's (QSR) With QSIT references

A complete compendium to FDA's Quality System Regulation (QSR) with relative references to FDA's Quality System Inspection Technique (QSIT). Now ONLY $99 (limited time)

Developing policies and procedures
Preparing for FDA audits
Responding to 483 Observations and Warning Letters
Conducting Internal Audits or determining Gap Analysis  

Search This Site

 Biological Indicator Reduced Incubation Time Study

(RIT)

Medical Device ethylene oxide sterilization is monitored by the use of biological indicators (BIs) using Bacillus subtilis species. The common “off the shelf” recommendation for incubation by most manufacturers is 7 days or more. However, there is a way to reduce the incubation time to as much as 24 hours.

Reducing the BI incubation time can be a big financial asset to an organization bent on reducing inventory. Other benefits including being able to matching customer demand and just having better overall control with regards to timing.



A lot of factors take part in the RIT including the sterilization cycle and the Challenge Pack (developed to mimic the device packaging – either equaling or making it more difficult for gas penetration). When a manufacturer decides to reduce the BI incubation time the method chosen to validate the process is very crucial in ensuring a) a successful time reduction and b) ensuring that the process is adequately validated to meet FDA requirements.

FDA Requirements

The FDA has proposed a method for validating a RIT. In summary the process works by subjecting a Lot of BIs to a Fractional cycle (or sublethal cycle – since the exposure time is significantly reduced). If done correctly a number of BIs will grow out. It is critical that the number stay within a range. The FDA recommends 30 to 80 percent survival.
The following is an excerpt taken from Premarket Notifications [510(k)] for Biological Indicators Intended to Monitor Sterilizers Used in Health Care Facilities; Draft Guidance for Industry and FDA Reviewers

You can read the document online at:

http://www.fda.gov/cdrh/ode/guidance/1320.html#tablenote_1


Obtain a minimum of 300 biological indicators. One hundred (100) biological indicators should be from each of 3 separate lots.

Using the predefined sterilization parameters, expose the biological indicators in 3 partial sterilization cycles (100 per partial cycle). Each of the test cycles will have 30% to 80% of the indicators surviving (i.e., test positive).

A partial cycle is one in which all sterilization parameters, except the time parameter, are met. The exposure time is much shorter than the standard sterilization cycle.

Only the biological indicators from one lot are to be used in each partial cycle. Do not mix biological indicators from different lots.

It is preferable to run biological indicators in a device load. However, the inherent difficulties of achieving a partial cycle kill under such circumstances are understood. Thus, partial cycles can be run without device loads.

NOTE: During all sterilization validation studies, consider the effects of the sterilant in combination with the device material on the indicator organism. If the materials are judged to have a significant effect on organism destruction, the biological indicators should be exposed to the sterilant in conjunction with the devices during the partial cycle studies.

If there are fewer than 30% survivors or more than 80% survivors in any one run, this particular run is invalid and should be rerun to achieve the desired number of survivors.

Three partial cycles are the minimum number of testing cycles to be run. If the results of any one cycle are invalid, another partial cycle should be substituted for it.

After exposure incubate the BIs for a minimum of 7 days. Place the BIs in the growth media no more than 8 hours after removal from the sterilization chamber or removal from the sterilized load of devices. Record the number of positive BIs on either a daily basis or for the particular time interval of interest.

Using the number of Bls that test positive on day 7 as the base of 100% grow out (denominator data), determine from the growth chart if the required number of BIs have grown out (numerator data) in the time interval in question. More than 97% of the base number of BIs should test positive in each partial cycle for the proposed incubation time to be acceptable.

The greatest number of days of incubation required to obtain more than 97% positive BIs (based on the 7 day incubation time) in any one of the partial cycles is the minimum incubation time that will be allowed. Averaging the three (or more) partial cycle incubation times is not allowable (see example in Appendix).

If the biological indicator user has not or cannot validate the biological indicator incubation period using the described methodology, then the user should remain with at least a seven day incubation period.

Number Positive Biological Indicators Required to Achieve 97% Growth
 

The numerator is the number of positive biological indicators that is greater than 97% of the denominator. If the numerator is equal to or greater than the one listed for the corresponding denominator (based on the total number of positive biological indicators on day 7), the length of the incubation time when this occurs is acceptable.

2 The denominator is the total number of positive biological indicators on day 7 of incubation.

Example: A manufacturer would like to reduce its biological indicator incubation time to 3 days. The test data show the following:

 

The 3-day reduced incubation time is not validated because, of the three valid partial cycles, not all achieved 97% growth in 3 or fewer days. However, based upon the criteria listed in #5 of the test methodology, the data validate a 5-day reduced incubation time. The 5-day incubation time in this example is the greatest number of days, from all the valid partial cycles, needed to grow out more than 97% of the denominator biological indicators.



* * * * * * * * * * * * * * * * *

Bier Vessels

The best way to conduct a RIT study is using a Bier vessel in a laboratory setting without the device load. Though many have argued that a Bier vessel does not closely enough mimic the “real” conditions there are many benefits.

For those of you not familiar, a bier vessel is a miniature sterilization chamber. The vessel allows for the rapid evacuation of gases, the rapid injection of Ethylene Oxide gas and finally the subsequent evacuation and elimination of sterilant from the chamber. This last point is very important for a successful RIT study. It is known that ‘residual kill’ can occur in the post gas dwell phase. The time to eliminate the gas is critical in ensuring repeatable results. Likewise using a full sterilization chamber can have unpredictable results – often costing you in a lot of unsuccessful runs.

Conclusion
In conclusion an ethylene oxide sterilization program can in fact compete with the quick turn-times seen by Gamma sterilization. Unless extra inventory and turn-time has no real benefits to your organization a RIT study can in turn quickly pay for itself. A reason RIT may not benefit you is if your product requires a lengthy degassing (or aeration) phase. Some products require weeks if not months before levels of Ethylene Oxide residuals drop to acceptable levels. If residual levels are not a concern having a RIT study as stated above can be rewarding.
 

Site Map »

Media package available for advertisers looking to advertise on this site.

Contact us | About Us | Sitemap
© Medical Device School 2003-2011