Drugsformulations

SOP on handling of Out of trend (OOT)

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

Responsibility:

•  Officer or above of QC laboratory.

 Accountability:

•  Head – Quality Assurance.
• Head – Quality Control.

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:

1. 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.
2. 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 , resuspenpendibility, 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 as appropriate for the dosage form.
• On observing OOT results analyst shall report to his / her supervisor.
•  Executive-QC / Nominee shall investigate cause for OOT results based on investigation  as per Annexure No.A01
•  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 out as per

Annexure No. A01

•    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 discovery.
• Each OOT investigation shall have its own identification number as per the following

procedure:

• Identification Number shall be as OOT-YYY-ZZ
•   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. ‘08’ for 2008
•  A typical identification number of OOT is OOT-001-08
• Where 001 is a serial number
•  and 08 stands for year 2008
•  Maintain a record of the number of out of trend (OOT) in a log book as per Annexure No.

A02

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List of Annexure / Format:

S. No.	Format Title	Annexure Number
1	Out of trend ( OOT ) investigation Report	A01
2	Out of trend ( OOT ) investigation log	A02

References (if any):

•  ICH (Q1A)

Reason for Revision:

• Scheduled Revision.

Abbreviation / Definitions:

• QC        :    Quality Control
•  SOP      :    Standard Operating Procedure
•  OOT      :    Out of Trend
• STP       :    Standard Test Procedure
•  SG         :    Sub-General
•  ICH        :    International Conference on Harmonization
• Id. No.   :    Identification Number

 

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: HPLC Id. No.:                                                                       UV-VIS. Id. No.: Balance Id. No.:                                                                    GC Id. No.: Dissolution Tester Id. No.:                                                    Others :
Brief description of the event:

 

Preliminiary Investigation:
Methodology	Yes	No	Comments
Physical apperance of the solution acceptable
Correct Potency of Inhouse / Reference standard used for calculation
Mobile phase was degassed properly before usage
Test and standard preparation as per approved test procedure
Appropriate glassware used as indicated in approved test procedure
Reagent used are appropriate and within shelf life
Correct wavelength used
Correct Normality / Molarity of Volumetric solution used
Correct inhouse / Reference standard used
Inhouse / reference standard used within expiry date
Correct filter used
Granules / tablets were ground properly
Correct dissolution Apparatus / rpm used
Calculation performed correctly
Integration parameter acceptable

 

Column	Yes	No	Comments
Correct column used ( e.g. pore size ,  dimension and make )
No leakage observed in column fitting
Raw data ( Particularly chromatogram  peak shape acceptable )
System suitability criteria meets
Conclusion / Recommendations:
Instrument	Yes	No	Comments
Instrument within the calibration period
Instrument set-up according to standard test procedure
Possibility of any leakage or air bubble in the system
Correct system parameter were used  during analysis
Electric and tubing system are correct for the system and column
Conclusion / Recommendations:

 

For related substance only:	Yes			No		Comments
Solution injected after freshly preparation
Peak of concern is an unknown impurity
Peak of concern is a degradation product
Peak of concern found is blank / Mobile  phase/ Placebo
Fresh blend used for sample preparation
Conclusion / Recommendations:
General	Yes			No		Comments
Same instrument available for  investigation
Same vials available for investigation
Same standard and sample solutions  available for investigation
5.4 Same column available for investigation
Conclusion / Recommendations:
Repeat Analysis ( Re-analysis )			Yes		No		Comments
Re-injection from the same vial to be  done
Re-filteration from the same final dilution  of  the sample
Re-dilution from the same stock solution  is done
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 / Nominee  Sign. / Date:

Annexure 2

OUT OF TREND ( OOT ) INVESTIGATION LOG

OOT Number	OOT Observation Date	Product Details	Batch Number	Test	Analyst	Date of OOT closure	Investigation closed By	Remarks

 

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