3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)

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SOP for Handling Out of Specification (OOS)

 MUBARAK PATEL  OCTOBER 24, 2020

OBJECTIVE
To describe the procedure for handling of Out Of Specification (OOS) laboratory
test results to ensure that the OOS test results are properly investigated and
corrective actions taken to avoid recurrence.

SCOPE
 This SOP shall be applicable at XYZ Ltd.,
This SOP is applicable to all the OOS results, which are obtained for Raw
Material, Semi Finished Products, Finished products and Stability samples.
If an out-of-specification results is generated for dissolution / drug release,
uniformity of dosage units, weight variation, disintegration and friability,
Preliminary investigation shall be carried out in such cases, respective
Pharmacopoeia guidelines or criteria shall be applied.
This SOP is not applicable to samples of various stages like scale up batches,
cleaning validation, swab analysis, Pre shipment samples, miscellaneous items,

description and solubility test and tests where tentative limits are given.

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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)
 This SOP is not applicable for OOS to tests like Bulk density, Sieve analysis,
Particle sizing and other physical parameters.
This SOP is not applicable for incomplete analysis (due to malfunction of
equipment’s) where results are not derived.

RESPONSIBILITY
 Chemist QC: To inform the OOS test result to the Superior or Manager QC: To
initiate the laboratory investigation on OOS test results and forward the
laboratory investigation report to Quality Assurance for final disposition, in case
of real OOS test.
 Manager-QC / designee: To review and approve all investigations of OOS
results before forwarding to Quality Assurance.
 Manager-QA / designee: To decide for final disposition of material / products.

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DEFINITION
 OOS: An unacceptable result that is the outcome of analysis. The result which
does not meet the pre-established specification of the test product shall be
termed as OOS (out of Specification) result.
 Evaluation samples: Samples, which are of deviation batch, recovery batch,
market complaint, pre-shipment sample, study and trial purpose.
 Questionable results: A result, which does not confirm but is out of limit at the
first analysis considered as questionable and needs to be investigated.
 Assignable cause: A cause that has been identified as the reason to invalidate a
questionable test result. The assignable cause is a conclusion derived from direct
or indirect evidence found during the investigation process, from the
interpretation of analytical data or a combination of both.
 Investigation: An investigation jointly conducted by an investigator and the
analyst. The purpose of the analytical investigation is to verify that a valid result
was obtained or discover what occurred to explain an invalid result .It must be
thorough enough to discover any analyst or equipment error, if one occurred.

PROCEDURE
 This procedure shall cover OOS test results and investigation
Definition: The term “OOS test results” includes all suspect test results that fall
outside the established specifications.
 Causes of OOS test result
An OOS test result can be due to

1. Assignable cause
2. Non-assignable cause 

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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)

 An assignable cause for OOS test result can be due to,

1. Laboratory error during analysis

2. Error in sampling, handling or storage of sample
3. Non-process related or Operator error
4. Process related error
5. Laboratory error can occur when an analyst makes a mistake in following the
method of analysis, uses a non-calibrated instrument, uses incorrect or
invalid working standard, does a mistake in calculation or any such other
reason associated with lab analysis.
6. All such laboratory errors shall be investigated during a laboratory
investigation (primary investigation), which shall be started immediately
upon getting an OOS test result.

Laboratory Investigation (Primary Investigation)

 The procedure described shall be followed if a laboratory test result for the
finished product sample fails to meet the established specifications. The flow
chart for investigating an OOS test result is given at the end of this procedure.
The analyst shall check the analytical data, for compliance with applicable
specifications, before discarding the test preparations.
 On obtaining an OOS test result, the concerned analyst shall immediately report
the OOS test result to his next superior through OOS notification (Annexure-1) and
OOS test result report (Annexure-2 and shall assign and register the OOS No. in
the OOS register by following the below order : OOS No. OOS/XXX/YYYY (XXX-
Serial No. , YYYY- Current Year)
 The analyst shall retain all the test preparations, glassware used, portions of test
POPULAR CATEGORIES
sample, sample blend, etc., till the review and investigations are concluded.
 The analyst and the immediate superior shall carry out a Laboratory
Quality Control Production
investigation as per the checklist (refer Annexure-3).
 The Laboratory investigation checklist shall cover various possible reasons Quality Assurance HPLC Engineering

involving laboratory operations such as: weighing, dilution, sample Microbiology Warehouse
preparation/work-up, labeling, glass-wares usage, cleaning of testing
Analytical Method Validation
tools/glass-wares, calculations, transcription of data and others listed in the
checklist. Pharmacopeia Qualification Packing

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Costing Insurance AHU

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Cleaning Interview Trading Video

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Repeat Analysis
Export GPAT ZyCoV-D
 If Laboratory investigation reveals that the OOS test result is due to laboratory
error then a repeat analysis shall be performed. The procedure followed and the
scientific rationale for concluding the laboratory error shall be properly
documented. POPULAR POSTS
 QC Head, in writing, shall give instructions for Repeat Analysis to a second
Analyst (Analyst-B). Analyst-B shall perform the repeat analysis in single. USP 2021 (United State
The repeat analysis shall be performed from the same sample portion, which Pharmacopeia 44 - NF 39)
 JANUARY 09, 2022
was used for the original analysis.
If this sample portion is not available, or is spoiled, then another portion of the
SOP for Preparation of Master
same larger sample pool / sample composite (previously collected for analysis)
Formula Record (MFR)
shall be used.  JANUARY 13, 2022

 If the batch meets the specifications during repeat analysis (performed after
finding a laboratory error) then the passing result shall be verified by a third Tablet Scoring Study of
analyst (Analyst-C) Azithromycin Tablets USP
500mg (Tablet Breakline
In case the repeat analysis by the Analyst-B gives an OOS test result, then the
Study)
batch shall be rejected. A secondary investigation shall be performed by the QA  JANUARY 04, 2022 
Head to find out the reason for batch failure.
Types of Tooling in
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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)
Types of Tooling in
 The batch shall be approved if Compression Machine
 MAY 28, 2020
1. The two repeat analysis results (by Analyst B & C) are within specifications.
2. For a quantitative determination the overall RSD for the two repeat analysis
What is the Expiry Date for HPLC
shall not be more than the following values: Mobile Phase?
 APRIL 24, 2022
Assay : NMT 2%
Related Substances/impurities : NMT 10%
Residual Solvents : NMT 15% 
The results shall be reported as an average of two repeat analysis (analyst B
&C) (refer Annexure-4). Oct 2020 (14)

The laboratory investigation report shall be prepared jointly by the analyst and
Head QC.
 The laboratory investigation report shall be handed over to QA Head. In case of TAGS
an identified laboratory error, the other samples/batches, which were analyzed
along with the initial OOS test sample, shall also be reviewed and the impact Accounts Audit Books Business
evaluated, along with implementation of the necessary corrective action plan.
 Re-sampling (for repeat analysis) shall be performed, only if an investigation of Cleaning Costing Export HPLC
the OOS test result indicates a sampling-error, as the reason for OOS test result.
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For re- sampling approval refer Annexure – 5)
Pharmacopeia Trading

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Secondary Investigation
When a laboratory error is not identified, an investigation shall be extended to USP 2021 (United State
the process area/manufacturing area for identifying any operator error / Pharmacopeia 44 - NF 39)
 JANUARY 09, 2022
equipment-related error / process-related error.
QA shall initiate ‘Secondary Investigation’ (Production investigation) by
SOP for Preparation of Master
approving the ‘Production Investigation Initiation’ form (Refer Annexure - 6). QA
Formula Record (MFR)
shall assign the production investigation number (PIN)  JANUARY 13, 2022

 Assigning a Production investigation number.

                          PIN / AAA / BBB (AAA-Serial No ; BBBB-YEAR) Tablet Scoring Study of
Azithromycin Tablets USP
QA shall conduct detailed production investigation along with respective
500mg (Tablet Breakline
production department and jointly prepare the ‘Production Investigation report’ Study)
(Refer Annexure - 7)  JANUARY 04, 2022

When complete investigation does not reveal any conclusive reason i.e. there is
a Non- assignable cause for the original OOS test result, QA shall recommend for
re – Analysis.

Re-analysis
 Re-analysis shall be performed on same sample / sample composite (i.e. same
portion of the sample used for original analysis / the same sample composite
previously collected for analysis) 
Re-analysis shall be done, in triplicate, by a different Analyst (Analyst-B), other
than the original Analyst (Analyst-A).
 In case one or more of the triplicate results of Analyst B is out-of-specification,
then the analysis shall be discontinued and the batch shall be rejected.
If all three results of the triplicate analysis performed by Analyst B, are within the
specification, then the analysis shall be repeated, in triplicate, by a third Analyst
(say C) for verification.
 The batch shall be approved if :

1. All the six individual results of Re-analysis are within the specification
2. For quantitative determination, the overall RSD of all the six values shall not be
more than the following values : 

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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)
Assay : NMT 2%
Related Substances/impurities : NMT 10%
Residual solvents : NMT 15%

  3. The difference between average value by the two analysts shall not be more
than the following values :
Assay : NMT 2%
Related Substances/impurities: NMT 10%
Residual solvents: NMT 15%
The average of average values reported by individual analysts shall be reported
on a certificate of analysis. 
 The original OOS test result shall not be averaged along with repeat analysis
results.
 The investigation shall be completed within 30 days of initial OOS occurrence.
In case of rejection of a batch, a thorough investigation shall be performed by
the Production Head and Quality Assurance Head to determine whether this OOS
test result is due to,

1. Process related. 
2. Non-process related error /operator error 

The secondary investigation report shall be signed by the Production Head and
QA Head.
 The QA Head shall communicate the Manufacturing Location Head and Head
QA about the rejected batch
OOS Investigation report shall outline the corrective actions necessary to save
batch and prevent similar recurrence.
The investigation shall be extended to other batches of the product, possibly
affected due to process related / non-process related error
 The investigation shall also be extended to other batches and other products,
possibly affected due to operator error or malfunctioning of equipment or poor
quality utilities etc.
 QA shall assess the overall investigation and recommend the corrective action
to be taken based on the investigation reports. (Refer to Annexure-8)
QA shall send a copy of the ‘Investigation Assessment Form’ to QC for release of
the result.
 QA shall retain the original OOS reports

REFERENCE(s) 
NIL

ABBREVIATION(s)
SOP - Standard Operating Procedure
Q.A - Quality Assurance
No. - Number
Q.C - Quality control
OOS - Out of specification
% - Percentage
RSD - Relative standard deviation

ANNEXURE(s)
Annexure - 1: OOS Notification
Annexure - 2: OOS Test Result Report
Annexure - 3: OOS Laboratory Investigation Checklist
Annexure - 4: Reanalysis / Retest Analysis Report of OOS Results
Annexure - 5: Resample Approval 
Annexure - 6: Production Investigation Initiation
Annexure - 7: Production Investigation Report
Annexure - 8: OOS Investigation Assessment Form
Annexure - 9: OOS Issuance No Record

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Page 1 / 19

REVISION HISTORY
Nil

Figure: 1 - OUT OF SPECIFICATION (OOS) PROCESS FLOW

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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)

Figure: 2 Out of specification Flow Diagram - Investigation of OOS Test Result

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3/23/23, 12:08 PM SOP for Handling Out of Specification (OOS)

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