SOP on Handling of Out of Trend (OOT)

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  • Objective:To lay down a procedure for handling of Out of trend for stability sample
  • Scope:This procedure shall be applicable for handling of out of trend of stability sample at quality control of pharmaceutical company name with location.
  • Responsibility:QC personnel shall be responsible to follow the procedure as per SOP.
  • Accountability:Department Head & QA Head shall be accountable for implementation of this SOP.
  • Abbreviations and Definitions:
  • SOP : Standard Operating Procedure; a document where step by step instructions are cited to serve as support for methods or manners of fulfilling a function or functions reliably and consistently.
  • OOT: Out of Trend
  • STP: Standard Test Procedure
  • ICH :International Conference on Harmonization
  • Procedure:
  • Criteria to consider a result as out of trend:
  • Result shall be considered as OOT and an investigation shall be done to evaluate the cause if following variations are observed:
  • Assay:
  • a)  5% change in assay from its initial value.
  • Related substances:
  • The result shall be consider as out of trend if:
  • For impurities ( individual or total ) between 0.1 % to 0.2 % the increase / decrease    in reported value is ±100% or more from the reported value in previous station for
the same individual or total impurity.
  • For impurities (individual or total) more than 0.2 % the increase / decrease in reported value is ± 50 % or more from the reported value in previous station for the same individual or total impurity.
  • The following are not treated as OOT:
  • a)  The value obtained from any individual impurity is less than 0.1%.
  • b)  If all the values are below the limit of quantitation. One or two data may be above the limit of quantitation.
  • C)  If there is an increasing trend of impurities.
  • Dissolution:
  • a) Failure to meet the acceptance criteria for dissolution for 12 units.
  • Other tests:Significant change in appearance, physical attributes or and functionality test (e.g. colour, phase separation,caking, hardness, dose delivery per  actuation) may be consider as out of trend. However some changes in physical attributes (e.g. softening of suppositories, melting of creams, partial loss of adhesion of transdermal products) may be expected under accelerated conditions and asappropriate for the dosage form.
  • On observing OOT results analyst shall report to his / her supervisor.
  • QC personnele shall investigate cause for OOT results based on investigation. An out of trend result can be due to
  • a) Assignable cause
  • b) Non-Assignable cause
  • Assignable cause for OOT results can be due to laboratory error.
  • Laboratory errors occurs when an analyst makes a mistake in following the method of analysis, uses incorrect working standard or wrongly calculation of data.
  • To confirm an error is a laboratory error an investigation shall be carried outas per Annexure.
  • If the investigation reveals that the OOT is due to laboratory error, then the sample shall be re-tested as per respective STP.
  • Repeat analysis shall be done in duplicate each by the original analyst (say A) and another analyst (say B) after taking the required corrective actions as applicable.
  • If on repeat analysis the results obtained are as per expected trend then the original testing results shall be invalidated and the repeat test results shall be reported.
  • When a laboratory error is not identified (non assignable cause ) then a repeat testing shall be planned in duplicate each by two different analyst (say B) and (say C). If the  repeat analysis results are within trend then the average of retest results shall be        reported.
  • If repeat analysis results obtained are still out of trend then initial OOT results shall be reported. Repeated results shall be identified as confirmatory results.
  • If OOT is confirmed , further trend of data shall be compared with the OOT values.
  • OOT investigation shall be completed within 30 days of its detection.
  • Each OOT investigation shall have its own OOT number as per the following    procedure: OOT Number shall be as OOT-YYY-ZZ
  • Where OOT stands for Out of Trend
  • YYY stands for serial number and started from 001 for each calendar year.
  • ZZ stands for year  e.g. ‘16’ for 2016.
  • A typical identification number of OOT is OOT-001-016.
  • Where 001 is a serial number and 16 stands for year 2016.
  • Maintain a record of the number of out of trend (OOT) in a log book as per Annexure.
  • Forms and Records (Annexures)
  • Out of trend ( OOT ) investigation Report-Annexure-I
  • Out of trend ( OOT ) investigation log-Annexure-II
  • Distribution:
    • Master copy – Quality Assurance
    • Controlled copies – Quality Assurance,Quality Control
  • History
Date
Revision Number
     Reason for Revision
 –
00
New SOP
                                                     Annexure-I            
Out of trend ( OOT ) investigation Report 
Product Name :
OOT Number:
Batch. Number:
Station:
Discovery Date:
Condition:
STP number:
Effective Date:
Analyst:
Test:
Specification:
OOT Initial Result:
Equipment Used:
Intrument ID.:
Balance Id. No.:
Brief description of the event:
Preliminary Investigation:
1.0 Methodology
Yes
No
Comments
1.1 Physical appearance of the solution cceptable
1.2    Correct Potency of     In-house / Reference         standard used for calculation
1.3    Mobile phase was degassed properly before usage
1.4    Test and standard preparation as per  approved test procedure
1.5    Appropriate glassware used as  indicated in approved test procedure
1.6    Reagent used are appropriate and within shelf life
1.7   Correct wavelength used
1.8   Correct Normality / Molarity of Volumetric solution used
1.9   Correct inhouse / Reference standard used
1.10 Inhouse / reference standard used  within expiry date
1.11 Correct filter used
1.12 Granules / tablets were ground properly
1.13 Correct dissolution Apparatus / rpm used
1.14 Calculation performed correctly
1.15 Integration parameter acceptable
2.0 Column
Yes
No
Comments
2.1 Correct column used ( e.g. pore size ,dimension and make )
2.2 No leakage observed in column fitting
2.3 Raw data ( Particularly chromatogram  peak shape acceptable )
2.4 System suitability criteria meets
Conclusion / Recommendations:
3.0 Instrument
Yes
No
Comments
3.1 Instrument within the calibration period
3.2 Instrument set-up according to standard test  procedure
3.3 Possibility of any leakage or air bubble in the  system
3.4 Correct system parameter were used  during  analysis
3.5 Electric and tubing system are correct for the system and column
Conclusion / Recommendations:
4.0 For related substance only:
Yes
No
Comments
4.1 Solution injected after freshly preparation
4.2 Peak of concern is an unknown impurity
4.3 Peak of concern is a degradation product
4.4 Peak of concern found is blank / Mobile  phase / Placebo
4.5 Fresh blend used for sample preparation
Conclusion / Recommendations:
5.0 General
Yes
No
Comments
5.1 Same instrument available for  investigation
5.2 Same vials available for investigation
5.3 Same standard and sample solutions  available for investigation
5.4 Same column available for investigation
Conclusion / Recommendations:
 
6.0 Repeat Analysis ( Re-analysis )
Yes
No
Comments
6.1 Re-injection from the same vial to be  done
 
 
 
6.2 Re-filteration from the same final dilution  of  the sample
 
 
 
6.3 Re-dilution from the same stock solution  is done
6.4 Resonication / Reshake due to incomplete insolublization
 
Conclusion / Recommendations:
 
Initial assessment Performed by/ Date:
Manager/ Nominee Review By/ Date:
 Comments and conclusion:
a)    Laboratory error ( Include explanation of error and data to be
      reported):
b)    No laboratory error
 
   Remendial Action:
Remedial Action required: An explanation of the remendial action required:
Retraining was performed ( attach training document):
No Remedial action required:
Analyst Sign. / Date:
 Manager  Sign. / Date:
                                                                            Annexure-II
                                    Out of trend ( OOT ) investigation log
OOT Number
OOT
Observation
Date
Product Details
Batch Number
Test
Analyst
Date of
OOT
closure
Investigation closed By

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