1.0 Purpose
1.1 This SOP covers evaluation of out-of-specification (OOS) and unusual results obtained in the laboratory testing.
2.0 Scope
2.1 The purpose of this SOP is to outline the requirements for handling of OOS results, including responsibilities, investigational actions and documentation. This includes addressing the batch(es) impacted, as well as correcting the cause to eliminate or minimize future occurrences.
3.0
Responsibility
3.1
It
is the responsibility of Head of Quality Control to assure that all test
results generated are accurate and valid. Quality Assurance has the ultimate
responsibility for investigations and therefore must be involved in all
investigations as well as approving all investigation reports and product
disposition decisions.
3.2
Head
of Quality Assurance is responsible for SOP Compliance.
4.0 Abbreviations and Definitions
4.1 SOP : Standard Operating Procedure
4.2 OOS : Out of Specification
5.0 Materials and Equipment
5.1 None
6.0 Precaution / Health and Safety Considerations
6.1 Everybody should follow the SOP of OOS handling. For OOS investigation data should be valid and accurate.
7.0 Procedure
7.1 Investigation Principle:
The purpose of an OOS investigation is:
7.1.1 To confirm the OOS result as VALID or INVALID, i. e. identify the OOS result as a laboratory error or as error in product itself by investigating analytical testing report.
7.1.2 To confirm the OOS result as VALID or INVALID, through Full Scale Failure Investigation i.e. involving Quality Control, In process control (re-sampling, If needed), Production, Quality compliance and other areas as applicable for identifying the root cause.
7.2 Initial Laboratory Investigation (ILI):
7.2.1 Any results deemed to be questionable (i.e. out of expectation, OOE) and does not meet established release / shelf life (for stability only) specifications (i.e. OOS) must be investigated in order to either verify the results or to invalidate the test results.
7.2.2 When unexpected results (either OOS or OOE) are obtained, analyst must inform Head of Quality Control or his/her delegate immediately (within the same day) and all test preparations (with documents) are to be retained, until the investigation is concluded, for further assessment of the test results.
7.2.3 Laboratory investigations must be expedited, taking priority over other assignments. In general the laboratory investigation needs to be completed within 5 working days (including re-testing).
7.2.4 The presumption must be made that the result is valid, until proven otherwise and any unusual circumstances or laboratory error should be investigated through the checklist provided in Annexure-III, with log book entry. The OOS reference numbering should be maintained as QC/OOS/YY/SN, where YY is the last two digit of the year (22, 23 etc.) and SN is the serial number of OOS of the same year.
7.2.5 In case if it is identified that an OOS/OOE results is due to one of the points listed in Annexure-III, the concern OOS/OOE result can be invalidated. The investigation report (Annexure-II along with other documents) must be documented in which reason behind the laboratory error must be mentioned along with corrective actions taken to prevent recurrence. Final disposition decision of the concern lot/batch will be taken based on re-testing as described in 7.2.6 to 7.2.8. This OOS document has to be attached with relevant location (e.g. in case of a lot/batch, compile with batch document).
7.2.6 The sample used for retesting must be taken from the same material that was originally used. Re-tests are performed by same analyst or a second analyst (if required), using the same equipment.
7.2.7 Under normal circumstances averaging of the original OOS results and the re-test result is not allowed but may be warranted for example in an HPLC assay where the test procedures require the test results to be determined by averaging peak responses from a number of consecutive, replicate injections (usually 2) from the same sample preparation, as defined in approved testing method. For some other tests, e.g. water content, it may be required to perform the test in duplicate (each individual result used for averaging must conform to specifications) and to report the mean value as the test result.
7.2.8 If the retest passes, the initial test result is to be invalidated and the result from the retest is taken for the release decision of the lot/batch. In this case (i.e. invalidated by re-testing) the rational must be fully documented and approved by Quality Assurance. If the retest confirms the initial OOS/OOE result, full scale investigation is to be performed. If the initial investigation concludes the reason for the OOS result to be inconclusive, then the initial OOS/OOE is considered valid and the investigation has to be extended to full scale.
7.3 Full-Scale Laboratory Investigation (FSLI):
The full-scale laboratory investigation includes:
a) Further confirmation or non-confirmation of the initial OOS test result by re- testing of the original sample.
b) Further evaluations for excluding laboratory error or by considering re-sampling.
7.3.1 Re-testing of original Sample:
The sample used for retesting must be taken from the same material that was originally collected from the lot. Retesting is performed three times than that of initial sample preparation (i.e. when testing monograph states single sample preparation, in this case three samples are to be prepared). Retesting should preferably be performed by an analyst other than the one who performed the original test, using the same equipment for the retest. If the retest passes (all retest results within specification), the initial test result is to be invalidated and the result from the retest is taken for the release decision of the lot/batch. In this case (i.e. invalidated by re-testing) the rational must be fully documented and approved by Quality Assurance.
7.3.2 Depending on the results of the retest and the conclusions of the full-scale laboratory investigation, re-sampling from the involved batch may be indicated if a clear sampling error can be established. Re-sampling is only allowed if the full-scale laboratory investigation shows that the original sample was not representative for the batch. This would be indicated for example, by widely varied results obtained from several aliquots of the original sample (if laboratory error can be excluded).
7.3.3 Under normal circumstances averaging of the original OOS results and the retest result is not allowed but may be warranted for example in an HPLC assay where the test procedures require the test results to be determined by averaging peak responses from a number of consecutive, replicate injections (usually 2) from the same sample preparation, as defined in approved testing method. For some other tests, e.g. water content, it may be required to perform the test in duplicate (each individual result used for averaging must conform to specifications) and to report the mean valued as the test result.
7.3.4 If the retest with same sample / re-sample (point 7.3.1 & 7.3.2) passes (all retest results within specification), the initial test result is to be invalidated and the result the retest is taken for the release decision of the lot/batch. In this case (i.e. invalidated by re-testing) the rational must be fully documented and approved by Quality Assurance. If the retest has confirmed initial failing test results and the findings of the investigation strongly indicate a product failure, in this case an investigation must be initiated as per relevant SOP of deviation and investigation involving relevant department. Batch disposition decision will be taken by the outcome of this investigation.
7.3.5 In general the full-scale laboratory investigation needs to be completed within a maximum of 20 working days (including re-testing).
8.0 Reference Document
8.1 In-house
9.0 Annexure
9.1 Annexure-I : OOS Investigation Flow diagram
9.2 Annexure-II : Log book of Out of Specification (OOS)
9.3 Annexure-III : Initial Laboratory Investigation (ILI)
9.4 Annexure-IV : Full Scale Laboratory Investigation (FSLI)
10.0
Revision
History
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Revision No. |
Brief
reason for the revision |
Effective Date |
Remarks |
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01 |
New |
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11.0 Training
11.1 Head of Quality Control or his/her nominee shall give the SOP training before effective date.
Annexure-II
Log book of Out of
Specification (OOS)
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Sl.
No. |
OOS
No. |
Product
Name |
Batch
No/ Lot No. |
Reason
of OOS |
Remarks |
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Annexure-III
Out of Specification (Initial Laboratory Investigation (ILI)
OOS Ref # QC/OOS/______ /______
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Product Name: |
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Material Number: |
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Batch/Lot Number: |
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Test |
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Requirement |
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Results found |
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Signature of Analyst |
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ERROR DETECTION BY
MEANS OF THE LABORATORY FAILURE INVESTIGATION
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Sl. No. |
Description of failure |
Yes |
No |
NA |
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1 |
External conditions satisfactory
(temperature, humidity) |
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2 |
Instrument parameter settings
correct |
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3 |
System suitability requirements
corresponding |
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4 |
Correct test procedure used (number,
version) |
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5 |
Test performance strictly complies
with the procedure |
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6 |
Reagents/solutions without deviations
(storage, purity, expiry date) |
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7 |
Reference standard without deviation
(weighing, dilution, storage, purity, expiry date) |
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8 |
Samples prepared correctly (e. g.
weighing, dilution) |
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9 |
Calculations performed correctly |
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10 |
Instrument calibration/service
correct |
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11 |
Retained solutions, glassware for appearance,
correct volume/size, free of contamination |
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12 |
Performance of analyses by trained
personnel |
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13 |
Samples OK (no peculiarities,
correct storage, representative) |
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14 |
Analytical history or history of
product (10 batches/ two years) |
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15 |
Other findings (description): |
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Comments & Recommendations:
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Investigated by:
Signature/Date:
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Evaluation after re-testing:
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Re-test findings:
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Analyst:
Checked by: |
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Comments from Head of QC: |
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Signature/Date: |
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Comments from Head of QA: |
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Signature/Date: |
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Corrective & Preventive actions: |
Close by/Date |
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1.
_____________________________________________________
2. _______________________________________________________
3.
_______________________________________________________
4.
______________________________________________________
5.
______________________________________________________
6. ______________________________________________________
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1. _____________
2. _____________
3. _____________
4. _____________
5. _____________
6. _____________ |
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Comments for Closing of
Investigation by Head of QA:
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Sign and date: |
Annexure-IV
Out of
Specification(Full-Scale Laboratory Investigation (FSLI)
OOS Ref
# QC/OOS/______/______
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Product Name: |
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Material Number: |
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Batch/Lot Number: |
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Test |
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Requirement |
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Results found |
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Signature of Analyst |
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Re-test findings using same sample:
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Analyst: Checked
by: |
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Re-test findings using re-sampling |
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Analyst:
Checked by: |
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Comments from Head of QC:
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Signature/Date:
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Comments from Head of QA:
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Signature/Date: |
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Corrective
& Preventive actions: |
Close
by/Date |
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1.
_______________________________________________________
2.
_______________________________________________________
3.
_______________________________________________________
4.
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1.
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2.
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3.
_____________
4.
_____________ |
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Comments
for Closing of Investigation by Head of QA:
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Signature/Date: |
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