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:
- 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 , 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 |
