Out of Specifications (OOS) Handling Procedure

A Standard Operating Procedure (SOP) for Out of Specifications (OOS) Handling Procedure results in the pharmaceutical industry is crucial for managing deviations from established specifications during the testing or manufacturing of pharmaceutical products. Below is a general outline for creating an SOP for handling Out-of-Specification results.


To describe procedure for reporting, investigating and responding out of specification (OOS) analytical results

Out of Specifications (OOS) Handling Procedure Scope

The scope of this document pertains to the OOS results in QC for Raw materials / Packaging materials, In Process and Finished Products for releasing at Pharmaceuticals Ltd


  1. It is the responsibility of all laboratory personnel working in QC to ensure that this procedure is performed as described and that proper supportive documentation is maintained.
  2. It is the responsibility of QC Analyst to inform out of specification results to the QC Manager or Supervisor.
  3. It is the responsibility of QC Manager or Supervisor and Analyst to complete OOS Form and investigate the cause of OOS.
  4. It is the responsibility of QA to issue OOS tracking number and allow to further investigate for root cause.
  5. QA ensures that this SOP is followed in its entirety.
  6. It is the responsibility of QA Head or Designee to approve this SOP.
  7. It is the responsibility of Director Operation to authorize this SOP.

Definitions & Abbreviations

  1. Out of specification (OOS) Results: A test that is valid, but the result does not comply with acceptance criteria or the established specifications.
  2. Retest: Repetition of a test(s) on another aliquot of the same sample or another container (e.g., vial) from the initial sample.
  3. Sample: The quantity of material taken according to an established sampling plan (e.g. item specifications, stability protocols) that is considered to be representative of the entire batch of material under test.
  4. Analyst A: A qualified and trained technical person performing the 1st test on 1st sample.
  5. Analyst B: A qualified and trained technical person with at least equal or more experience than the Analyst A.
  6. Analyst C: A qualified and well trained technical person with more experience and training than Analyst A and Analyst B. Analyst C should be the subject matter expert.
  7. Assignable Cause: A documented and scientifically justified determination that an anomalous result can potentially be traced to an error in the laboratory or in processing.
  8. Un-Assignable Cause: When the cause of test failure cannot scientifically be determined.
  9. Resample:  A new sample taken from the collection of the batch. A resample is warranted when it is demonstrated that the original sample is neither representative nor homogeneous, is contaminated, or has been exhausted/consumed in testing.
  10. Reference Sample: A sample solution used for comparison purpose during the investigation, which is re-measured and/or reworked parallel to the sample solution in question. Initial results obtained from the control sample should be reliable and as expected from the testing performed.
  11. Material Review Board (MRB): A team comprising of Head of Quality Assurance, Quality Assurance Manager, Quality Control Manager, Production Manager and Material Manager Head to resolve the issues related to the quality of materials and its impact on the product quality.
  12. SOP: Standard Operating Procedure
  13. QM: Quality Management
  14. OOS: Out of Specifications
  15. cGMP: Current Good Manufacturing Practices
  16. HOD(s): Head of Department(s)
  17. QA: Quality Assurance
  18. QC: Quality Control
  19. PR: Production


Out of Specifications (OOS) Handling Procedure

Expected type of errors:
  • Type 1: Laboratory Error e.g. analyst error, incorrect calculation, malfunctioning of equipment, use of incorrect standards or sample preparation, lack of precision and mis-measurement etc.
  • Type 2: Non-process related or operator error in manufacturing i.e. human or mechanical error, which occur during manufacturing e.g. failure to add a component, malfunction of equipment or cross contamination.
  • Type 3: Process or manufacturing error due to poor control over processes e.g. incorrect mixing, heterogeneity of blends etc. Confirmation that this was the cause of OOS error will constitute a product failure.
  • Type 4: If no process error / Laboratory error is observed during the investigations and results of the tests, constitute a product failure.

OOS Tracking Number

QA assigns a number to each OOS as given below;
OOS / YY / 0000
OOS: Out of Specification
YY: Year in which OOS is initiated and recorded.
0000: Sequential Number of OOS in a calendar year.
Example: OOS / 23 / 0001 is the First OOS of QC Department for the year 2023.
QA maintains a logbook for the OOS and records the information along with OOS tracking Number (Annexure B).
After confirmation of the OOS, relevant person requests QA to assign OOS tracking number.

Stage 1: OOS Investigation (Annexure A)

  1. While carrying the test by Analyst “A”, if the result of test is found out of specification, analyst is to complete “General Section” of form QA/FRM/0000/00, record the result (Stage 1A) and preserve sample, standards and dilution.
  2. The analyst must inform QC Head / Designee of the OOS result immediately after confirmation of the occurrence.
  3. Analyst and QC Supervisor jointly complete investigation section of Form QA/FRM/0000/00.
  4. If any error is found upon investigation (assignable cause), correct the error and same sample should be reanalyzed by the same analyst “A”. Enter result in Stage 1B investigation.
  5. If the result meets specification, consider test passed and release the material.
  6. If the result of investigation is indeterminate (un-assignable cause), proceed to Phase II OOS investigation (Stage 2).
  7. In case the knowledge of Analyst A is not satisfactory, replaces the analyst.

Stage 2: OOS Investigation (Annexure B)

  1. Full scale investigation Stage 2 is performed from production / warehouse to find out if the factor causing OOS is a result of deviation / manufacturing error / sampling error.
  2. If the root cause is found to exist from manufacturing / sampling the Stage 1 QC test will be declared invalid and resampling is performed.
  3. Risk assessment and CAPA are generated to conclude the problem.
  4. If no error or root cause is found from manufacturing / sampling then retest from the same sample is performed.
  5. Allow the test to be performed by Analyst “A” and “B” either on the same sample or on resample.
  6. Forwards the results of Analyst “A” and “B” to Stage 3 investigation.
Note: Resampling should be performed by the same qualified, validated methods that were used for the initial sample

Stage 3: OOS Investigation (Annexure C)

Four possible scenarios to consider:
  • Scenario 1: Analyst “A”, FAIL and Analyst “B”, FAIL
  • Indicate product / material fails specifications: Reject the material.
  • Scenario 2: Analyst “A”, PASS and Analyst “B”, FAIL or results difference is above 3% from each other.
  • Allow the test to be performed by Analyst “C”. If result difference is within 3% of pass result, accept material. If fail or result difference is above 3%, indicate product / material fails specifications.
  • Scenario 3: If analyst “A” FAIL and Analyst B, PASS or results difference is above 3% of each other)
  • Allow the test to be performed by Analyst “C”. If result difference of Analyst C is within 3% of pass result of Analyst B, accept material. If fail, indicate product / material fails specifications.
  • Scenario 4: If Analyst “A” PASS and Analyst “B” Pass, Accept the material, if results difference are within 3% of each other.
  • Out of Specifications (OOS) Handling Procedure
  1. In case of Scenario 2 and 3, Analyst “C” performs test on the same sample tested by Analyst A and B.
  2. If test passes, Analyst “C” repeats test on the same sample used in Stage 1 (results should be within 3% of the previous results).
  3. QC Head / Manager is to record the result of investigation in Stage 3 of Form (QA/FRM/0007/01) and report results.
  4. QC Head / Manager gives the assignable root cause at the end of investigation (if any), then it is forwarded to MRB.

MRB Investigation Out of Specifications (OOS) Handling Procedure

  1. If material fails or there is a failure to give an assignable cause to failure of test at Stage 1, 2 or 3, investigate on the investigation section of the Form (QA/FRM/0000/00).
  2. State the Formal investigation indicates the investigation is forwarded to the MRB for further evaluation of possible root cause and for determination of corrective action or preventive action.
  3. If the material fails specifications, E-mail notification is sent to all the concerned departments.
  4. The MRB will make a decision regarding quality / regulatory impact and disposition of the material(s) / batch(s) and complete the Formal investigation (QA/FRM/0000/00).
  5. Obtain result on the investigation, conclusion Form (QA/FRM/0000/00).
  6. OOS is finally closed and archived by QA.
  7. In case OOS is not closed successfully, MRB will take the final decision for further proceedin

Attached Documents (Forms / Annexure)

  1. Flow Diagram for Handling OOS (Stage 1) (Annexure A)
  2. Flow Diagram for Handling OOS (Stage 2) (Annexure B)
  3. Flow Diagram for Handling OOS (Stage 3) (Annexure C)
  4. Format of Log Book for Out of Specifications (Annexure D)
  5. OOS Investigation Report (QA/FRM/0000/00)
  6. Out of Specifications (OOS) Handling Procedure

Reference & Linked Documents

  1. FDA Guidance for Industry: Investigating Out of Specification (OOS) results for Pharmaceutical Production
  2. WHO: Good practices for national Pharmaceutical control Laboratories
  3. SOP for Management of Documents
  4. SOP for Change Control
  5. SOP for Quality Risk Management
  6. SOP for  Corrective Action & Preventive Action

Revision History

Revision No. Date Responsible Person /Designation Description of Change
01 15.02.22 QA Manager To update the SOP as per requirements
02 28.05.23 QA Head To update the SOP and form as per “SOP for Management of Documents” and Major Flow changes as per Document Change Request
03 17.07.23 QA Head To update SOP as per discussion with Auditor, flow changes in stage 2 and stage 3, relevant changes in flow diagram and OOS form

Annexure D: Format of Log Book for OOS

General Section                       

Sample Name: ______________________________                       SOP number: ________________________
Lot No.: ___________________________________                        Product Stage: _______________________
Title of SOP: _______________________________                        Specification: _______________________
Effective date of SOP: _______________________                         Analyst / Department: _________________
OOS Generated by: __________________________                        OOS Tracking Number: _______________

QC Head Sign / Date: ________________________

Stage 1A: Analyst A, First Test Test Result (first test): ___________
Specification: _______________Does not conform QC Investigations: The following step should be taken as part of supervisory assessment. 

Out of Specifications (OOS) Handling Procedure

Details of investigation                                                          Yes                   No·

  • Analyst knowledge and performance of test satisfactory
  • Raw data obtained in the analysis are satisfactory
  • Identification of Anomalous or suspect information
  • Is the calculation used to convert raw data values into final result are significantly sound, appropriate and recorded correctly
  • Is the performance of instrument acceptable
  • Are appropriate reference standards, solvents reagents, and other solutions were used and  they met QC specifications
  • Evaluation of performance of test method to ensure that is performing according to standard based on method validation data and historical data
  • Has the analyst  properly trained and competent to perform test
  • Instrument calibration checked
  • Clean glassware used
  • Laboratory error exists and tests results are invalid

Remarks of QC Head:                         Satisfactory                                               Not satisfactory

Stage 1B: Analyst A, Second Test (In case of assignable cause) Retest Result (second test):______________

  • Specification: _________________ 
  • Analyst A: ____________________
  • QC Head: ____________________
  • Stage 2: Full Scale OOS Investigation from Production / Warehouse
    Reason for Investigation: _______________________________________
  • Aspects of Manufacturing / Sampling that may have caused the Problem: __________________________
  • Results of Documentation Review (BPR) of probable cause: ______________________________
  • Problem occurred previously: __________________________________________
  • Description of Corrective Action(s) taken: ___________________

Resampling The material is allowed to be re-sampled with the authorization from QA.

Sample Quantity: ____________________                                          Authorized By/Date: _______________
Resampled By/Date: __________________                                         Sample ID: _______________________

Stage 3: OOS Investigation
Date of Re-test: ______________________ Analyst A Name: _____________________Analyst B Name: __________________
Result of Analyst A: _______________

Result of Analyst B: _________________________

Results are within 3% limit:                            Yes                              No
In case of Scenario 2 and 3:
Analyst C Name: _____________________
Result of Analyst C: ___________________
If Result passes, Analyst C also performs test on the sample used in Stage 1
Result of Stage 1 sample by Analyst C: _______________

  • Results are within 3% limit:                            Yes                              No
  • Sample preparation Accurate:                         Yes                            No
    Factor affecting batch quality present:            Yes                            No

Assignable Root Cause (if any): _________________________
Comments: _________________________________________

Analyst A: ____________________ 

Analyst B: ____________________

Analyst C: ____________________

QC Head: ____________________

MRB Investigation List of Participants: 

  1.  _________________________________
  2.  _________________________________
  3.  _________________________________
  4.  _________________________________
  5.  _________________________________
  6.  _________________________________

Investigation by MRB: _______________________

  1. Possible Root Cause Analysis: ______________________________
  2. Corrective & Preventive Action: ________________________________ 
  3. Conclusion: ___________________________

OOS Closed Successfully:                             Yes                            No
If No, give reason: ___________________________      

Quality Assurance: ___________________________        

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