BI Failure Investigation in Moist Heat Sterilization Process | Das, Palash Chandra
Biological Indicator Failure Investigation
Using biological indicators in the steam sterilization process helps validate that the conditions to
kill microorganisms were met. The BI is exposed to the sterilization process and then incubated to
determine whether any endospores survive. If no spores survive or grow, the test is a pass. A
passing result demonstrates that the sterilizer is effective in killing a large number of highly
resistant bacterial spores.
But what if the test is a fail? It could be caused by several factors, including operator experience,
load preparation and sterilizer condition. When a positive culture results after processing the BI in
a validated steam sterilization cycle, finding the cause is critical. Majorly investigators are
interested to review such failure investigation which has potential impact on the product sterility
and patient safety. If we review the last 10 years 483’s trend the major concern area is inadequate
failure investigation.
If a failed BI occurs in your department, it is an alarm that something is wrong but can also create
a positive learning experience for your sterilization staff to stop and examine process and
procedure.
Finding true Root causes from a failure investigation is like iceberg what we assume or realize that
is 10% of the iceberg and what we misinterpret or ignored that is 90% of the iceberg which is not
visible and submerged in the water. In the agile terms, the visible iceberg is about DOING agile,
and the submerged section is more about BEING agile.
Use of Robotics and Artificial Intelligent (AI) are the evolving techniques in modern pharmaceutical
manufacturing and medical device industries. Robots, which can perform the repetitive task
otherwise handled by human operators.
Drawback of BI failure investigation is we can’t suddenly understand the failure unless growth is
observed, or lower log reduction is realized through enumeration after incubation. BEING agile
always directing towards continues process develop, monitoring, review and release. Sterility
assurance program is widely correlated with product design to throughout the product self-life.
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BI Failure Investigation in Moist Heat Sterilization Process | Das, Palash Chandra
Sterilization is one of the most critical process steps or manufacturing sterile products. In this
article we will be discussing about moist heat sterilization process. In these applications,
Geobacillus stearothermophilus spores are primarily used due to their high resistance to these
sterilization processes.
Review sterilization cycle parameter
Check sterilization display/ Printout – Confirm if there are an error or alarms
Critical parameters met for the intended cycle
Review and evaluate if any undesirable events or interruptions during cycle
Review External Chemical Indicators, or Process Challenge Device (PCD) Indicator
Confirm the BI & CI used are validated for the cycle
Confirm the PCD or BI is not expired
Review storage of PCDs or BI – Whether stored outside of recommended conditions
Review Process for Handling and Placement of the PCD
If not using a pre-assembled PCD, was it correctly built? – Use of self-content or dilution or
sport suspension from master stock
Appropriate challenge population and tolerance (D-Value)
Review placement of PCD in the chamber (How & Where) – placement should be
considering the worst-case simulations / cold spot / or representing the penetration sensor
positioning
Confirm Proper BI Activation And incubation – Was correct process followed, incubation
temperature and incubator used.
Investigate Potential Error in Load Preparation, packing and handling
Load configuration – Overloading or improper loading pattern can cause the BI failure
Load placement – Incorrect loading container / trollies
Load type – Appropriate fill volume and container configuration, selection of surrogate or
product solutions (change in viscosity)
Mixed up with treated (exposed in sterilization conditions) and nontreated (positive
control) BI unit
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BI Failure Investigation in Moist Heat Sterilization Process | Das, Palash Chandra
Figure 1: Fish Bone Diagram on BI failure
If the failure cannot be attributed to any cause listed – Its’s time to explore other opportunities
like, sterilizer performance (e.g operation, calibration, breakdown and maintenance issues) , Utility
supply , inhouse or third party microbiology laboratory evaluations (e.g analyst , method , testing
or evaluation technique, cross-contamination and record keeping ).
Getting appropriate root case will reduce the chance of recurrence.
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BI Failure Investigation in Moist Heat Sterilization Process | Das, Palash Chandra
References/ Additional reading resources:
PMF Newsletters, Volume 17, Number 5, May 2011.
procedure.[Link]
Variations in the Resistance of Biological Indicators Used to Assess Sterilization;IVT,By Tim
Sandle, [Link]
used-assess-sterilization
Positive Biological Indicators, [Link]
[Link]
POTENTIAL CAUSES OF A POSITIVE BIOLOGICAL INDICATOR,
[Link]
f%20a%20positive%20BI%[Link]
BI Checklist: Troubleshoot a Positive Biological Indicator in Steam Sterilization, November
8, 2018 Technical Tip,
[Link]
indicators-for-steam-sterilization
Author Details:
Palash Chandra Das
M. Pharma in Pharmaceutical Chemistry > Click here for LinkedIn Link
Core Technical Area:
Qualification & Validation , Sterility Assurance, QMS, Investigation, Risk Management
Blogs: [Link] ; Email: [Link]@[Link]
Please find our YouTube channel link, [Link]
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