1. No category

Handling of out of specification
results
Michael Koupparis
University of Athens
Handling of out of specification
results
1.0
Purpose:
To provide instruction for handling
of out of specification results.
2.0
Objective:
To provide a documented procedure
for handling of out of specification results.
3.0
Scope:
This procedure is applicable for
handling of out of specification results.
4.0
Responsibility:
– Primary: Officer – QC
– Secondary: Officer-QA / Officer-QC
5.0
Procedure
Initiation of OOS (Phase I):
• QC chemist shall report to QC In-charge, as and
when he notices out of specification.
• The analyst should retain the entire sample /
standard solution.
• QC In-charge shall initiate Phase I investigation as
per the format given in the SOP
• Initial results have to be reported along with the
certificate of analysis and worksheets.
• Then the investigation is to be done by QC Incharge for the following types of the OOS failure:
5.0
Procedure:
• Material failure: Review and Comparison of the party
certificates of analysis of raw material used.
– Material shall not match the specifications.
– If OOS is identified, reject the material.
•
Production: Change in reaction time / sequential
addition of the components / Functioning of the
equipment / review of BMR (Batch Manufacturing
Record).
– If OOS is identified reject the product of the reprocess
– If OOS does not identified, investigate as laboratory error.
•
Laboratory: In laboratory, there are four possibilities
for error:
5.0
Procedure:
• Clerical error: Correction to be made according to
clerical error, training shall be given to analyst. And
release the material.
• System failure: Power failure / calibration failure check
/ any spillage or contamination in standard and sample /
unsuitable instrument is used / instrument parameters
set incorrectly.
• Analyst failure: Errors in dilution / Usage of appropriate
and valid standard / method followed / sample stored
appropriately / status of balance / Homogeneity of the
sampling procedure / status of Instruments.
• Sampling procedure failure: Sample preparation
method followed / sample taken is representative /
sampling plan followed / sampling equipments status.
5.0
Procedure:
• If not found from all the above-mentioned
failures, product can be considered as the
material failure on the basis of trend
analysis.
• The QC In-charge will fill the phase I
investigation form with duly signed to QA
for further actions.
• Upon conclusion, and remark initiation of
the OOS phase-II is to be done.
5.0
Procedure:
Phase II investigation of OOS:
• Nature of OOS is to be decided as per
phase- I conclusion.
• Reason / Remark is to be noted for the
nature of the OOS.
• Repeat testing can only be performed
after an investigation of failure is initiated.
5.0
Procedure:
Phase II investigation of OOS:
• Determine if the cause of the OOS is based on
clerical error.
– If the review of the OOS result demonstrates the
result is attributable to error based on incorrect
calculation, transcription error, etc. correct the entry
(ies) in accordance with current laboratory notebook
entry error corrections procedure and re-review the
result.
– If the corrected result is within specifications and
acceptable based on historical test result trends,
record and report the result.
– A formal investigation report is not required in this
case.
5.0
Procedure:
Phase II investigation of OOS:
• Conduct additional analyst training and/or
review the test or process procedure for
clarity to minimize future inconsistencies.
5.0
Procedure:
• If the preliminary investigation of the OOS result
demonstrates the result is attributable to a
determinate analytical identifiable error(s) (e.g.
non-adherence to monograph instructions,
instrument response drift, observed
technique/instrument abnormalities, etc.):
– the OOS result is recorded in the laboratory
notebook with suitable explanation as part of the
batch or process record, and
– repeat testing can be performed.
– This initial OOS result, demonstrated to be
attributable to determinate error, is not considered in
the final release of the material or process
5.0
Procedure:
• When the investigation demonstrates that
the OOS result is attributable to
determinate analytical identifiable error:
– conduct repeat testing by the original analyst
A following any corrective action indicated by
the investigation.
– Record and report the repeat results.
– These repeat results are considered in the
final disposition of the material or process.
5.0
Procedure:
• If the preliminary investigation of the OOS test
result demonstrates that it is not attributable to
determinate identifiable error, but is attributable
to indeterminate error (unknown):
– Document the conclusion of the investigation.
– Record the results in the laboratory notebook and
include as part of the batch or process record.
– This initial OOS result is considered in the final
disposition of the material or process.
5.0
Procedure:
• Where repeat testing is warranted after the
investigation has disclosed indeterminate
error:
– repeat the test in duplicate by the original
Analyst A and another Analyst B on the
original sample unless the preliminary failure
investigation demonstrated that the original
sample was non-representative.
5.0
Procedure:
• Note: If the initial aliquot from the original
sample is not sufficient for retest, a second
aliquot from the original sample is used.
• In the event that the original sample has
been consumed during analysis, a second
sample (new sampling) can be used.
• Re-sampling / Re-processing is to be done
in case of the sampling procedure failure /
In-process sample failure.
5.0
Procedure:
• If one or both repeat results of Analyst A
are out-of-specification and one or both of
repeat results of Analyst B are out-ofspecification:
– record both repeat results of Analyst A and
Analyst B and the original OOS results of
Analyst A as part of the batch or process
record.
– Indicate the material as failing the
specification.
5.0
Procedure:
• If both repeat results from Analyst A and
both results from Analyst B are within
normal specification range (review
historical result trend):
– record all repeat results as part of the batch
or process record.
– Indicate the material as passing the
specification.
5.0
Procedure:
• If one or both results from Analyst B are
out-of-specification and both results of
Analyst A are within normal specification:
– record both repeat results of Analyst A and B
and the original OOS results of Analyst A as
part of the batch or process record.
– And based on the trend analysis material to
be rejected or re-sampling to be performed
and re-test by analyst B.
5.0
Procedure:
• If re-test results of Analyst B are out-ofspecification:
– record re-test results of Analyst B and the
original OOS results of Analyst A as part of
the batch or process record.
– Indicate the material as failing the
specification.
5.0
Procedure:
• If re-test results from Analyst B are within
normal specification range (review
historical result trend):
– record re-test results as part of the batch or
process record.
– Indicate the material as passing the
specification.
5.0
Procedure:
• When an OOS result has been
demonstrated through laboratory
investigation to be valid and reflects the
true quality of the material:
– an investigation is initiated to determine the
cause of the material failure.
– The Product Failure Investigation, if required
based on the outcome of the OOS
investigation, must be completed.
5.0
•
Procedure:
Phase II concludes with the result of
material / product-released / not released.
• Attach the available certificate of Analysis
and worksheets of all the tests conducted.
• Mention preventive / Further action.
• Final closure by QC In-charge and
approval by the QA In-charge.
Intimation of the OOS (1)
• Intimate to materials departments and corporate
QA of the OOS in case of rejection.
• QA Chemist to fill the final rejection note.
• This note should include the following things:
OOS No. / Item code / Used for / Item name /
Date of receipt / Control no. / Supplier’s
consignment no./ Supplier’s name / Referred
specification no. / Reason for rejection.
Intimation of the OOS (2)
• Party Certificate Of Analysis, XXXXXXXXX
Pharmaceuticals Ltd Certificate Of Analysis and
samples if available should be attached with the
rejection note.
• Forward this to the material department for
further action.
• If the frequency of the out of specification
exceeds more than three times, then the vendor
shall be black listed in case of raw / packing
material and if in-process then the process shall
be considered for change.
6.0
•
•
•
•
•
Reference Documents
Phase I Investigation Form
Decision Tree of Phase II
Phase II OOS Form
Final rejection note
OOS logbook.
6. LOG BOOK FOR OUT OF
SPECIFICATION RESULTS
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Serial no: ………………….
OOS no: ……………….
Date: ……………………
Department: ……………
OOS details: …………….
Investigation details: …….
Signature of QA: …………
Remarks: …………………
7.0
•
•
•
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Abbreviations:
QA = Quality Assurance department
SOP = Standard Operating Procedure
QC = Quality Control
OOS = Out of specification
8.0
Copies to Distribution Sites :
• QA - Quality Assurance department
• QC - Quality Control
OUT OF SPECIFICATION INVESTIGATION FORM
Format No.: SOP/QA/XXXX/F/1
Parameter
Limit (Spec. No) Actual
Result
Pass / Fail
Pass / Fail
Attachement:
First CoA with
Work sheet
Phase-I
Analyst failure
(Yes / No)
•
Is there any Error in calculation?
• Is there any Error in dilution?
• Are appropriate and valid standards and
reagents used?
• Are methods
followed?
Phase-I
Analyst failure
(Yes / No)
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•
•
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Are the test parameters
followed?
Is sample stored appropriately?
Is the balance used with appropriate accuracy and
calibrated?
Is the sample Homogenous?
Is the calibrated instruments/Glassware
used?
Is the analyst trained and
evaluated?
Phase-I
System failure
(Yes / No)
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To check for Power
failure
Are the system/Instruments are calibrated? (Calibrate
again)
Is the calibration standard Used
appropriate?
Is there any spillage/contamination in
Standard/sample?
Is suitable instrument
used?
Is the instrument parameters set
correctly?
Are the Appropriate Equipment Accessories used?
Phase-I
Sampling Procedure failure
(Yes / No)
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Is Sample preparation done properly?
Is sample taken representative?
Is sampling plan followed?
Are sampling equipments ok?
Were environmental conditioned OK during Sampling?
Is Appropriate Sample container / Sample bag Used?
Phase-I
Other Checks for In-process Sampling
(Yes / No)
• Check if there is change in reaction time.
• Is the Sequential addition of components followed?
• Is functioning of equipment proper?
• Is BMR/BPR (Batch Manufacturing Record / Batch
Process Record) reviewed and found OK?
• Review & comparison of Party COA of Raw
Materials.
Phase-I
Conclusion
System Failure / Analyst Failure /
Sampling Failure / In-process Failure /
Material Failure.
(According to the above conclusion initiate
the OOS Phase II as per flow chart)
Phase-I
Remark:
QC In charge (Name/ Signature/ Date)
__________________________________
Authorized By: QA In Charge
(Name/Sign/Date)
_______________________________
FINAL REJECTION NOTE
Format No.: SOP/QA/xxxx/F4
Material/Product:
Process/Stage:
Lot/Batch No.:
Lot/Batch size:
To: Purchase Department / Plant
Manager
xxxxxxxxxxxxxx
From: QA Site
Date of Initiation
Date of Sampling
OOS Number
Manufacturer’s Name:
DATE:
Please note that the following item is finally rejected:
Details:
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Item Code:
•
Used For:
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Item Name:
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Date of Receipt/Manufacturing
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Control No./Batch No.:
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Quantity Received:
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Quantity Rejected:
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Supplier’s Consignment No.:
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Supplier’s Name:
•
Ref. Specification:
REASON FOR REJECTION:
Further Action Plan:
QA In charge
Enclosure:
Party COA, ---------------------- COA and Samples
Cc To: Corporate QA, Supplier through Purchase Department