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SOP for Investigation of Sterility Test Failure


Standard operating procedure for conducting investigation for failure of sterility test.

1.0  Objective

       To clearly define the process for conducting investigation for failure of sterility test. This will find out whether the sample actually fails or it is an error due to test or analysis in the laboratory equipment and area malfunction and equipment malfunction in production or laboratory

2.0  SCOPE

       This  procedure is applicable to OOS results of sterility test of finish product only carried out in  microbiology laboratory.       

3.0  Responsibility

3.1  Doing      :   Technical Assistant/Executive
3.2  Checking :   Executive/Manager

4.0  AccountAbility

       Head  of the Department  

5.0  Procedure

5.1  Definition OOS :

       This term includes all suspect results that fall outside specifications on acceptance criteria establishedby the manufactures in official compendia in product registration dossier or any other form of legal documents.   

5.2  Laboratory  Investigation

5.2.1  Inform  to Q.C incharge immediately when OOS results occurs, in laboratory notification form as per Annexure – I.
5.2.2  Complete the investigation  check list and report as per annexure - II.
5.2.3  Check negative control for no growth.
5.2.4  Identify the organisms for positive test from the growth of sample.
5.2.5  Try to find the source of organisms in laboratory as well as in manufacturing area.
5.2.6  If no cause is found, reject the batch.
5.2.7  If cause is found, perform a retest on the same number of the sample.
5.2.8  If no evidence of microbial growth is found on retesting, the preparation being examined passes the test for sterility.
5.2.9  If the evidence of microbial growth is found on retest, the preparation being examined fails the test for sterility.
5.2.10  As per IP if evidence of microbial growth is found, preparation being examined does not comply with the test for sterility.
5.2.11  Do not repeat the test unless it can be clearly shown that the test was invalid for causes unrelated to the preparation being examined.
5.2.12  The test may consider invalid only when one or more of the following conditions are fulfilled.
5.2.12.1  If microbial growth is found in the negative controls.
5.2.12.2  Data on microbial monitoring of the sterility testing facility show a fault.
5.2.12.3  A review of the testing procedure used for the test in question reveals a fault.
5.2.12.4  After identifying the micro organisms isolated from the containers showing microbial growth, the growth may be ascribed without any doubt to or the technique used in conducting the test procedure.
5.2.13  If the test is declared to be invalid repeat with the same number of unit as in the original test. It no evidence of microbial growth is found in the repeat test, the preparation being examined complies with the test for sterility. It microbial growth is found in the repeat test and conformed microscopically the preparation being examined does not comply with the test for sterility. 
5.2.14  Prepare laboratory investigation report with complete details as per annexure – III and submit to QA for their approvals and further investigation if necessary.

6.0  ABBREVIATIONS :

       O.O.S  = Out of Specification



ANNEXURE - I  
LABORATORY INVESTIGATION NOTIFICATION FORM                                                                                                                            
INVESTIGATION REPORT NO: ____________________________________
Name of Product  : __________________________________________
Batch No.              :________________________
Batch Size            : _______________________


SUMMARY OF PROBLEM : __________________________________________

Out of Specification result : ____________________________________________

                                              ___________________________________________

Equipment malfunction
Sample preparation error
Procedural error
Other
Assignable cause not apparent
Microbiologist error

Report By    : _____________________                                       Date : _____________

Checked By : _____________________                                       Date : _____________
          



    



ANNEXURE - I                               
                                LABORATORY INVESTIGATION NOTIFICATION FORM                                                                                                                           

INVESTIGATION REPORT NO: _____________________________________
Name of Product  : __________________________________________
Batch No.              :________________________
Batch Size            : _______________________


   SUMMARY OF PROBLEM : __________________________________________

Out of Specification result : ____________________________________________

                                              ___________________________________________

Equipment malfunction
Sample preparation error
Procedural error
Other
Assignable cause not apparent
Microbiologist error

Report By    : _____________________                                              Date : _____________

Checked By : _____________________                                              Date : _____________
          




        ANNEXURE - II
QUALITY CONTROL.DEPARTMENT
                                                     CHECKLIST                                         PAGE  1 OF 2
No.
 Particulars
Yes
No
A
Environment


A1
Are the count of sterility room by settling  plate test above action level ?


A2
Are  the viable count  of all area of sterility testing room by Rodac plate and
swab above action  level? 


A3
Are  the count obtained in gowning  and finger print above action level ?


A4
Is the fumigation properly carried out?


A5
Are the non viable count observed within the limit?


A6
Are the floor cleaned with respective disinfectant  and according to schedule?


A7
Are the LAF  cleaned as per the schedule  with respective disinfectant ?


A8
Is the last DOP test carried out as per the  schedule  and satisfactory?


A9
Is the LAF in proper working condition with respect to pressure drop.?


B
Personnel monitoring correlation


B1 Correlation of environmental monitoring (lab) ,surface and personnel monitoring isolate with organisms observed in sample?


B2
Co-relation of environmental  monitoring (mfg.) surface and personnel 
monitoring isolate with the organisms observed in the sample?


C
General


C1
Is the filtration assembly working, properly assembled and sterilised  ?


C2
Is the autoclave validated or not ?


C3
Is UV lamp in working period ?


C4
Is the incubator under controlled temperature?





        ANNEXURE - II
QUALITY CONTROL.DEPARTMENT
                                                           CHECK LIST                                       PAGE 2 OF 2
No
Particulars
Yes
No
C
General


C5
Were media used before expiry ?


C6
Is there any evidence that  contaminated media was used ?


C7
Is the culture used for the control have transferred as per schedule ?


C8
Is the culture used for the  positive  control have been activated by 3-4 transfer  ?


C9
Is the master culture from ATCC ?


C10
Is the approved method used for sterility testing  ?


C11
Was the test method followed correctly ?


C12
Is the -ve control kept or not during testing and growth found or  not ?


C13
Growth observed in –ve control tube ?


C14
Is there any evidence that  sampling done is not proper ?


C15
Is there as similar history with the product in past ?


C16
Have there been similar errors in the past ?


C17
Is microbiologist trained ?


C18
Is  microbiologist enough experience ?


C19
Has microbiologist sufficient job knowledge ?



Report By : _____________             Date of Report : _____________          Checked By : ___________


ANNEXURE – III
LABORATORY INVESTIGATION REPORT
 Page No : 1 of  2

NAME OF PRODUCT/MATERIAL : _____________________BATCH NO/AR NO : ______________

DESCRIPTION OF PROBLEM : _______________________________________________________
                                                       ____________________________________________________________________________________
TEST : _______________________        TEST DATE : _______________ SOP : __________________

ANALYST : ____________________    RETEST DATE : __________________
(RESAMPLED)

LABORATORY INVESTIGATION :

ASSIGNABLE CAUSE IDENTIFIED :
Explanation : _______________________________________________________________________________
ASSIGNABLE CAUSE NOT IDENTIFIED :
Explanation : ______________________________________________________________________________

ACTION TAKEN TO PREVENT RECURRENCE : _______________________________

Prepared By (Q.C) : _________________                          Date : _______________
Checked By (Q.C) : _________________                          Date : _______________
Approved By (Q.A) : __________________                      Date : ________________




ANNEXURE – III
LABORATORY INVESTIGATION REPORT
Page No : 2 of  2
INVESTIGATION REPORT NO : _____________________________

ADDITIONAL INFORMATION :

Additional information required : Retest date and reasons for retest, all participants’ names, all original and retest results, evidence for the conclusion and names of individuals responsible for the corrective action.

If other additional information is available concerning the nature of the problem, diagnostic tests to be performed, more detailed results of the investigation or suggested corrective action, explain below or attach a memo to this form.
Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
Email: .moc.enilediugamrahp@ofni Need Help: Ask Question


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