CONTROLLED DOCUMENT SOP73-242 Status: Effective Effective Date: 19/Sep/2022

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BAUSCH & LOMB INCORPORATED

STANDARD OPERATING PROCEDURE
HIDDEN RIVER

TITLE: Laboratory Investigations

Approvals Required (Electronic copy of signatures on file)

Author
QC Chemistry
Quality Assurance

REFERENCES:

• 27.1.8-NSOP Laboratory Investigations

• 27.1.1-NSOP Non Conformance Management

• 27.1.12-GSOP Escalated Quality Event

• 27.1.10-NSOP Field Alert Reporting

• 20.1.1-NSOP Corrective Action and Preventative Action Reporting

• SOP75-029 Chemical Action and Out of Trend Limits Stability Program

• SOP73-240 Procedures for Chromatography

• SOP73-077 Procedure for Governing the Documentation, Interpretation, Review and

Reporting of Analytical Data Generated by the QC Chemistry Laboratory

• SOP73-110 Procedure for the Use, Maintenance, and Retrieval of Controlled

Laboratory Documentation in QC Chemistry and IQI

• SOP72-079 Documentation and Review of QC Microbiology Laboratory Data

• GUIDANCE FOR INDUSTRY: Investigating Out-of-Specification (OOS) Test Results for

Pharmaceutical Production, October 2006

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1.0 PURPOSE

This procedure defines the process for conducting out-of-specification (OOS) out of action
limits (AL) and out-of-trend (OOT), analytical laboratory investigations. This procedure
defines a uniform and clear path for problem solving, decision-making, retesting, data
reporting and documentation of investigations. This procedure is designed to ensure that
laboratory investigations are carried out in a consistent and timely manner, that the
assignable cause(s) or most probable cause(s) is identified, and that the risk is assessed and
addressed. This procedure also ensures that corrective action(s) are promptly implemented
to prevent reoccurrence and that tracking and trending mechanisms are employed to ensure
compliance.

2.0 SCOPE

This procedure applies to analytical tests of cGMP materials and products, in support of
commercial manufacturing. The procedure includes an investigation of atypical
chromatography such as unknown peaks, OOT, and OOS results. This procedure should
be followed for antibiotic potency assay testing.

This procedure does not apply to the obvious errors listed below:

• Documentation errors: events in the lab that are not OOS/OOT (testing) related.
These are documented and corrected where applicable and/or investigated per the site
non-conformance process, where applicable.

• Power outage – analyst and supervisor or designee document the event, note power
failure, and analysis to be repeated on associated analytical documentation.

• Testing error – the spilling of the sample solution, incomplete transfer of the sample,
or incorrect preparation. Original and new sample prep worksheets must be provided
for review and kept in the same analytical packet.

• Calculation error – analyst and supervisor or designee review and both initial/date
the correction.

• OOT/OOS testing results received from a contract laboratory. The contract

laboratory’s investigation procedure(s) will be followed for these situations. The
investigation, conclusion, and report detailing the OOS or OOT results generated by
the contract laboratory will be communicated, reviewed, and approved by Management
as specified in the individual quality agreement.

• Instrument errors or system suitability failures, including check standard failures,

prior to the injection of samples. These issues will be documented in the instrument
logbook, where applicable; and on the related testing documents (i.e lab worksheets).

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• OOT/OOS result for stressed stability studies (accelerated stability samples) with a
previously confirmed failure or where degradation/change is expected to occur.

NOTE: It is recommended that accelerated and expired stability samples are to be

run after all finished product/in-process samples are analyzed finishing with the
bracketing standard; thus, creating essentially two independent sample sets.

Each "sample set" before and after bracketing standard shell be processed
independently.

When an expired stability sample(s) is (are) tested and OOS/OOT result is (are)
generated the disposition of the lots (long-term stability, finished product, or in-
process samples) tested within the same analytical run and that is (are) and have not
generated OOS/OOT results may be determined while the investigation is open and
those samples may be dispositioned independently on the hard copy and E-Systems.

• Stability OOT results which are generated at or past expiry test interval and testing
after expiry which is typically performed only for internal information purposes.

• Stability OOT results trending downward for attributes with a specification limit of
NMT (i.e. impurities, weight loss gain) or for OOT results trending upward if the
specification limit is set as NLT (i.e. droplet size).

• Repeated OOT stability results for a particular test; once an initial LIR is created for
an OOT of that test, further LIRs for that test in that study will not be created for
continuing the same OOT. The original LIR will be referenced for additional OOT
instances. A stability assessment of the expiry must be included with the data/results
report to support the disposition of generated data.

• Repeated weight loss/gain (WLG) stability OOS results; once an initial LIR is
created, further LIRs for that study will not be created for continuing WLG OOS. The
original LIR will be referenced for additional OOS instances.

• Testing performed for engineering studies or development studies for products that
will not be commercialized or be included as part of a regulatory filing. These failures
are investigated as part of the R&D processes.

• OOT/OOS result or non-conforming testing performed for training purposes

• Incorrect Instrument parameter – Incorrect wavelength, flow rate, sample size, etc.
The analyst and supervisor will document the event and annotate incorrect instrument
parameters and VOID original data.

• System suitability failure – System accuracy, precision, repeatability, or specificity

requirements were not met.

2.1. For all examples listed above and other instances that are the same/similar in nature,

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the analyst and supervisor or designee will document the event on the applicable
worksheet/e-record.

2.2. With QC management approval, the analyst will abort the initial work performed and
restart the test.

2.3. QC management will document the approval in the appropriate laboratory notebook or
on the appropriate form/worksheet/chromatogram.

2.4. The analysis is to be repeated as soon as possible using the same sample preparation
(in case of equipment-related errors) or fresh prepared from the same sample set in case
of the testing preparation error, spills, etc., and properly documented.

2.5. The original data set is to be VOID. The original (VOID data) and repeated data sets
must be reviewed and disposition accordingly.

2.6. In the case where data has been processed, any result regardless if the result is within
the specification, OOT, or OOS during the original analysis shall not be
accepted/considered in the product acceptance determination.

3.0 RESPONSIBILITY

Analyst

• Be aware of potential problems that could occur during the testing process and
watch for problems that could create inaccurate results. Analysts should not
knowingly continue an analysis they expect to invalidate at a later time for an
assignable cause.
• Ensure that only instruments and equipment meeting established performance
specifications are used and that instruments are properly calibrated prior to use.

• Notify QC management if any errors were encountered during the preparation

phase of testing, (i.e. sample solution spill, discolored sample solutions, dilution
errors, etc.), or any instrument problems were encountered during the analysis
phase (i.e. leaking pump, temperature excursion, the air bubble in a flow cell, etc.).
Do not continue the preparation or analysis if an error is suspected to have occurred.
A laboratory investigation is not required at this point in the process. The analyst
will document the cause of the known error in the appropriate laboratory
notebook(s) or on the appropriate form/worksheet. Clearly written justification, for
decisions, must be provided even when the reasons seem obvious. With QC
management approval, the analyst will abort the initial work performed and restart
the test. QC management will document the approval in the appropriate laboratory
notebook or on the appropriate form/worksheet.

• Initiate a laboratory investigation report within 24 hours of issue identification.

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• Retain all data (including any invalidated data) for review during the final audit
phase at the conclusion of testing.

• Retain all testing solutions until final results have been calculated. Do not discard
any solutions, volumetric glassware used in the analysis, or consumable materials
where appropriate (disposable filters, syringes, HPLC vials, etc.), until the
OOS/OOT and any related investigation have been closed and affected material
dispositioned.

• Retain samples or test preparations until the data is checked for compliance, the
data is reviewed, and the laboratory investigation is completed.

• Do not add additional injections, re-measure or resample prior to initiation of the

LIR.

Quality control management or designee

• Perform the investigation in a timely and objective manner. Target Phase I
investigation completion within 24 hours.
• Do not include preconceived assumptions as the cause of the OOS/OOT results
• Determine if an immediate re-examination of the actual solutions, test units, and
glassware might provide more credibility for lab error in the original measurements
or preparations.
• Determine the significance the OOS values represent to the laboratory quality
system.
• Document activities and outcomes
• Manage LIRs to ensure investigations are closed within the specified time period.
• Monitor and trend investigations to ensure repeat/problematic areas and associated
root cause(s) are addressed

Stability
• Provide stability assessments of the product, including trend data and shelf-life
predictions, where applicable and required.

MQA/Quality Assurance
• Review LIRs for completeness, correctness and concurrence prior to closure.
• Determine if the event qualifies as an Escalated Quality Event and/or requires Field
Alert Report according to local site procedure in the event of a marketed stability
nonconformance or nonconformance for material used at multiple locations.
• Approve re- test/re-sample plans in both Phase I and Phase II of the investigation
process.
• Approve Laboratory Investigation
• Lead Phase II cross-functional team investigations

4.0 DEFINITIONS

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Aberrant Data – Data, in the reviewer’s judgement, which deviates from the expected
value and can be defined as either unexpected, questionable, irregular, abnormal or deviant
but is still within applicable specifications.

Action Limits - Internal limits (typically tighter than release specifications) based on
release criteria, release history and stability projections available

Analyst Error – An error attributed to a mistake by an analyst.

Assignable Cause – A cause for a discrepancy is assignable which can be proven or

reproduced by correction of input data or an experiment. Examples are analyst error,
instrument error, sample preparation error, etc.

Field Alert Report - Written notification to the Food and Drug Administration (FDA)
concerning any failure of a distributed batch to meet any of the specifications established
in an application.

Laboratory Error – An assignable cause attributed to the laboratory (i.e. analyst error,
equipment malfunction, etc.) that resulted in the specific OOS or OOT result. When
possible, the cause should be verified by observational findings, experimental data, re-
measure or hypothesis testing.

Laboratory Sample – A set of representative units collected from a lot of material or

product and submitted to the laboratory for testing.

Nonconformance report (NC) – CQMS element for evaluating and dispositioning non-
conforming materials or products.

Obvious Error – A clear error due to external circumstances that the analyst has detected
prior to generating data. Examples include:

• Calculation error
• Power outage
• Equipment failure
• Testing errors (sample preparation errors, solution/reagents/standards or
glassware errors)
• Incorrect Instrument parameter, incorrect instrument set up or equipment
• System suitability failure

Out of Specification (OOS) Result – An examination, measurement, or test result that

does not comply with pre-established specifications (i.e filed applications, drug master
files, approved marketing submissions, official compendia, or internal acceptance
criteria).

Out of Trend (OOT) - A result that does not follow the expected trend, either in
comparison with other manufactured batches or with respect to historical data for
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the product. For finished product release testing, OOT results include any values
outside established control limits. The result is not OOS but does not follow the
pattern of previous or expected results. A statistical model can be applied or a
manual evaluation of the data can be used to determine if a result is OOT. For
accelerated studies that have a “significant change” as defined by the VICH guidelines,
investigate as an OOT result.

Probable Cause – Possible reason for a given result but data must be gathered to confirm
it is the root cause.

Re-dilution – Repeating necessary dilution(s) using the original stock sample and/or
standard solutions and measuring the test results of the re-diluted working solutions.

Re-filter – The process of filtering an aliquot of the final sample preparation dilution
prior to the analysis being performed.

Re-injection - Re-injection of the original vial.

Re-measure – Additional examination of the original sample preparation with the

purpose of determining if the subject result can be attributed to instrument error, the
sample, or its preparation. (Re-injection, re-vial, re-dilution, and re-filter)

Repeat testing – Phase I testing utilized to provide scientific justification for overcoming
an OOS result for known laboratory error.
Reportable result – Final reported statement of quantitative/qualitative analysis as
defined by test procedure. In the event of a laboratory investigation, it is the result(s)
reported after completing the investigation

Retest Plan - Detailed pre-defined, pre-approved written procedure, including criteria for
acceptance of results, which requires QA approval. This is used in Phase II
investigations.

Re-Test – A new sample preparation from a sample provided as part of the original
laboratory sample.

Re-sampling – A new sample of the original container/homogenous material. An

additional sample was submitted for testing which is taken from the same population but
at a different time than the original laboratory sample.

Re-vial – A second vial (GC/ HPLC) of the original working solution to be analyzed

Root Cause – The most basic reason for a given result. The point at which intervention
could reasonably be implemented and expected to change performance and prevent future
recurrence of an undesirable outcome.

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Unknown (Extraneous) peak – A peak not previously noted in the method validation or
identified in other studies for assay and preservative methods. The peak is not present in
the placebo, diluent, blank(s), or mobile phase and cannot be established as system
carryover, or system/gradient artifact, and is above the limit of quantification for the
method.

5.0 PHASE I INVESTIGATION

The purpose of the Phase I investigation is to provide an initial assessment of the accuracy
of the data generated by the laboratory. During this phase of the investigation, the
hypotheses regarding laboratory error or instrument malfunctions can be tested using the
original test preparations. At no point should an investigation’s sole purpose be to
invalidate a result. This represents an inadequate investigation and can give the impression
of testing for compliance. If the initial assessment indicates no meaningful errors were
made in the analytical method used to arrive at the data, a full-scale OOS investigation
should be conducted (Phase II).

5.1. The analyst or designee should initiate the investigation in the CQMS system. It is the
responsibility of the analyst to fill out the Phase 1 Investigation Form and include the
form with data package for review. OOS results associated with long term stability
samples require immediate verbal notification to Quality Control and Quality
Assurance management. The field alert clock starts when an initial OOS is generated
and management notification must occur immediately.

5.1.1. In the event CQMS is unavailable, use the attached forms to document the
investigation activities and attach them to CQMS when the system becomes
available.

5.2. A Phase 1a investigation is conducted to determine if an obvious error occurred. The

attached checklist should be used as a guide to ensure that all relevant aspects are
considered. The following are examples that are encompassed in a Phase 1a
investigation and which are to be included in the CQMS record and documented as
outlined in the bullets below:
• Calculation error – analyst and supervisor review and both initial/date the
correction.
• Power outage – analyst and supervisor document the event, note power failure
and analysis to be repeated on associated analytical documentation.
• Equipment failure - analyst and supervisor document the event, note equipment
failure, and analysis to be repeated on associated analytical documentation. Cross-
reference maintenance record.
• Testing error – the spilling of the sample solution, incomplete transfer of the
sample, or incorrect preparation. The analyst must document immediately.
• Incorrect Instrument parameter – Incorrect wavelength, flow rate, sample size,
etc. The analyst and supervisor document the event, annotate incorrect instrument
parameters, analysis to be repeated on all associated analytical documentation.
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• System suitability failure – System accuracy, precision, repeatability, or specificity

requirements were not met.
• For examples listed above and other instances that are same/similar in nature, the
analysis is to be repeated, documented using the same sample preparation (in case
of equipment-related errors), or fresh prepared from the same sample set in case of
the testing preparation error.

5.3. If an obvious error is not noted as part of the Phase 1a investigation, a Phase 1b
investigation will be initiated. The attached checklist should be used as a guide to
ensure that all relevant aspects are considered. A supervisor or designee should assess
the following as part of the Phase 1b investigation and document the results in the
CQMS record.

• The test method used and confirm analyst knowledge of and performance of the
correct procedure. Ensure training was provided where specific training is
required/applicable.
• Examine the raw data obtained in the analysis, including chromatograms and
spectra, and identify anomalous or suspect information. Use pictures to preserve
evidence that will not be retained at the conclusion of the investigation.
• Verify that the calculations used to convert raw data values into a final test result
are scientifically sound, appropriate, and correct; also determine if unauthorized or
non-validated changes have been made to automated calculation methods.
• Confirm the performance of the instruments
• Determine that appropriate reference standards, solvents, reagents, and other solutions
were used and that they met quality control specifications. In cases were the solutions
were prepared in-house, confirm the accuracy of the preparation.
• Evaluate the performance of the test method to ensure that it is performing
according to the standard expected based on method validation data and historical
data.
• Chromatography should be reviewed for unknown peaks or atypical peak shapes,
especially those present in assay or preservative methods.

5.4. Quarantine all associated equipment and reagents concerned whenever possible until
they can be excluded as a cause of the OOS result.

5.5. Samples with atypical physical characteristics should be documented and brought to
the attention of QC management and QA. Samples should not be excluded from testing
plans unless justified and approved by QA.

Remeasurement plans should be launched in CQMS prior to performing re-

measurement activities. Additional preparations from the laboratory sample or
additional samples are not permitted as part of the Phase I investigation, unless
approved by QA.

5.6. Laboratory testing results should be overcome when the Phase I investigation shows
clear and scientifically supported evidence that a laboratory error exists.
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5.6.1. If a laboratory error is unequivocally identified, single repeat testing may be

initiated at the point in the process immediately prior to where the error occurred.
If insufficient material remains, single repeat testing must be performed on a new
sample preparation.

5.6.2. The impact of the assignable cause identified on other analyses, laboratory systems,
and batches/lots must be addressed and documented in the investigation report. This
should include analyst performance, OOS trends associated with the method,
instrument or analyst, and whether other batches may be impacted by the probable
cause.

5.6.3. CAPA, including retraining, should be considered to limit occurrence of further

laboratory errors when applicable. If no CAPA is required, justification should be
provided.

5.7. When evidence of laboratory error remains unclear, a full-scale OOS investigation
should be conducted to determine what caused the unexpected results. It should not be
assumed that OOS test results are attributable to analytical error without performing
and documenting an investigation.

5.8. The Phase I investigation will be considered completed when the LIR investigation is
closed in the CQMS system. Phase II (full scale) investigation, when necessary, will
be executed under the NC module in CQMS.

6.0 PHASE II INVESTIGATION

When the initial assessment does not determine that laboratory error caused the OOS result
and testing results appear to be accurate, or a laboratory based root cause could not be
identified, a full-scale OOS investigation should be conducted. The objective of such an
investigation should be to identify the root cause of the OOS result and take appropriate
corrective and preventative action.

6.1. When the Phase I investigation does not determine that an error caused the OOS result,
a Phase II investigation will be performed. This phase of the investigation will be led
by Quality Assurance.

6.2. An investigation may involve other impacted departments including, but not limited to:
manufacturing, process validation, facilities, etc.

6.3. Prior to further testing, a manufacturing investigation should be started to determine

whether there was a possible manufacturing root cause

6.3.1. If a manufacturing deviation can be substantiated as the cause of the OOS,

additional laboratory investigation may be terminated and the product rejected.

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6.3.1.1. The impact to other products/lots must be evaluated prior to closing the
investigation.

6.4. Stability OOS/OOT

6.4.1. If abnormal results are found at any stability interval which predicts the test results
may be out of specification before the next testing interval, schedule additional
testing before the next scheduled testing interval to better determine appropriate
actions to be taken.

6.5. Once an investigation task is received in CQMS for Phase II testing, extended lab
testing may commence.

6.5.1. Hypothesis testing may be completed to help confirm or discount a possible root
cause. A testing plan and acceptance criteria must be established and approved prior
to performing the testing. This is considered investigational testing and may not be
used to replace an original suspect analytical result. It may be only used to confirm
or discount a probable cause.

6.5.1.1. The hypothesis description should detail the theoretical root cause being
investigated, what samples will be testing, the exact execution of the testing
and how the data will be evaluated.

6.5.2. Multiple hypotheses may be tested as part of the investigation.

6.5.3. If an assignable cause cannot be determined through hypothesis testing and all
potential causes have been discounted, retesting may be considered.

6.5.4. If hypothesis testing reveals an assignable cause, the original data is invalidated,
and retesting is completed.

6.6. Retesting/resampling is carried out to confirm or invalidate the initial OOS result based
on a sufficient number of analytical results.

6.6.1. The sample used for retesting should be taken from the same homogenous material
that was originally collected from the lot, tested, and yielded the OOS result, if
available. It may be a second aliquot from the same sample that was the source of
the failure.

6.6.2. The retest plan is based on the variability of the analytical method, the difference
to the specification limit and the concrete circumstances of the analytical test. Any
statistical review for %RSD and repeatability should relate to the values obtained
during method validation. Generally, 5X retest is performed by a second equally or
more qualified analyst.

6.6.3. If further OOS results are identified and confirmed, testing may be terminated

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before the maximum number of assays is performed.

6.6.4. Re-sampling is only performed if the investigation concludes that the original
sample was not representative of the batch, if the remaining sample amount is not
sufficient for the retesting or if the sample was not handled/stored properly.

6.6.4.1. The re-sampling should be performed by the same qualified methods that were
used for the initial sample. However, if the investigation determines that the
initial sampling method was in error, a new accurate sampling method shall
be developed, qualified and documented.

6.6.5. Individual data from initial and retesting must be provided to Quality assurance for
evaluation and consideration in the release decision.

6.7. No OOS results identified during Phase II retesting

6.7.1. If all analytical values of the retesting are within specification limits and an
assignable cause has been found or a most probable cause has been detected, the
initial OOS result is not confirmed. All individual analytical results obtained under
retesting are reported on the associated report form (FCS, PRSC, IPCS, stability
coversheet, RMXA, or RMXB) and considered for final batch disposition.

6.7.2. The impact of the assignable/probable cause identified on other analyses,

laboratory systems, and batches/lots must be addressed and documented in the
investigation report. This should include analyst performance, OOS trends
associated with the method, instrument or analyst, and whether other batches may
be impacted by the probable cause.

6.7.3. CAPA should be considered to limit occurrence of further laboratory errors when
applicable. If no CAPA is required, justification should be provided.

6.7.4. When an investigation does not reveal a cause for an OOS result and the OOS result
is not confirmed by retesting, the OOS result should be given full consideration in
the batch or lot disposition decision. If no laboratory or calculation errors are
identified in the first test, there is no scientific basis for invalidating initial OOS
results in favor of passing retest results. All test results, both passing and suspect,
should be reported (QC documents and Certificates of Analysis), and considered in
batch release decisions. Any decision to release a batch should come only after a
thorough investigation has shown that the OOS result does not reflect the true
quality of the batch. This may include a review of all other tests related to the batch
and other batch historical data. In making this decision, Quality Assurance should
always err on the side of caution.

6.7.5. Where results are close to the specification limits, whether above or below the
specification, all individual results, including any OOS result(s), are reported and
considered for final batch disposition

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6.8. OOS results identified in Phase II retesting

6.8.1. If one or more of the individual results of the retesting plan are OOS, and an
analytical error is excluded, the passing results are no more likely to represent the
true result for the sample than that the OOS result(s). For this reason, the batch
should be treated as an OOS batch. The initial OOS result and any additional results
obtained under retesting are to be reported.

6.8.2. Once a batch has been rejected, there is no limit to further testing to determine the
cause of the failure so that corrective action can be taken. The decision to reject a
batch cannot be reversed because of further testing.

6.8.3. The impact of the OOS result on other batches, on going stability studies, validated
processes and testing procedures should be determined by Quality Assurance and
Quality Control and be documented in the conclusion, along with the appropriate
CAPA.

6.8.4. A determination should be made if the material is used at other sites. If the material
is used at multiple locations, Quality Assurance should notify other sites through
the escalation process.

7.0 TIME FRAME FOR INVESTIGATION

7.1. Target completion of the Phase I OOS/OOT investigations within 3 business days of
the initiation date. The awareness date is considered day 1.
7.2. Complete Phase II OOS/OOT investigations within 30 calendar days of the Phase I
initiation date. The Phase I initiation date is considered day 1. If this is not possible,
an extension must be requested and approved by QA.

8.0 DISPOSITION OF THE AFFECTED MATERIALS:

8.1. When an expired and accelerated stability sample(s) is (are) tested and OOS/OOT
result is (are) generated the disposition of the lots (with the expiry and at the expiry
long term stability studies, finished product lots, or in-process samples) tested within
the same analytical run and that have not generated OOS/OOT results may be
determined while the investigation is open and those studies/lots/samples may be
dispositioned independently on the hard copy and/or E-Systems.

8.2. Affected materials (stability studies, product lots) shell be dispositions based on the
investigation findings and current applicable procedures (i.e 27.1.1-NSOP: Non
Conformance Management)

9.0 ATTACHMENTS:

Attachment A:Process Flow

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CONTROLLED DOCUMENT SOP73-242 Status: Effective Effective Date: 19/Sep/2022

CONFIDENTIAL
This is Proprietary Information SOP73-242 Rev. 2

10.0 FORMS CONTROLLED OUTSIDE THIS SOP:

SOP73-242 Form A: Phase 1 Investigation

SOP73-242 Form B: Phase 1a Investigation Checklist

SOP73-242 Form C: Phase 1b Investigation Checklist

SOP73-242 Form D: Phase 1b Investigation Conclusion

10.0 REASON FOR REVISION:

CR-000344535, 07/22: Added section 8.0: Disposition of affected materials,

revised Attachment A (Process flow chart). Minor
clarifications and formatting throughout document to fulfil
chages required by QCR 467693.

CR-000182540, 05/19: New site procedure which combines some content from
WI73-227 into one procedure.

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CONTROLLED DOCUMENT SOP73-242 Status: Effective Effective Date: 19/Sep/2022

CONFIDENTIAL
This is Proprietary Information SOP73-242 Rev. 2

Attachment A: Process Flow

Phase 1a Lab
Investigation

Obvious Error No Error Found

Document and Sta rt Pha se 1b

correct invalid result Investigation

No further action Investigation by

required analyst & supervisor

Close LIR

Assignable
cause?

Assignable Cause – No assigna ble cause

Root cause or error remains
identified unclea r

Test Data
Invalidated
Generate CAPA Close LIR

Repeat analysis a nd
record results

Phase II
Investigation (NC
initiated)

Extended Lab Manufacturing

Investigation Investigation

Assignable
No Assignable Results Confirm Assignable
Cause
Cause OOS Cause

Hypothesis Invalidate
Testing original results Disposition Ba tch
No further
retest

Retest Report retest

results

Resample

Generate CAPA

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>
CONTROLLED DOCUMENT SOP73-242 Status: Effective Effective Date: 19/Sep/2022

CONTROLLED DOCUMENT
SIGNATURE PAGE
Document Name :SOP-000182552

Document Title :Laboratory Investigations

Document ID :SOP73-242

Signed By Date (GMT) Justification

Mujagic Anita 14/Jul/2022 Functional Approval

19:07:29

Perry John 18/Aug/2022 Quality Approval

16:33:21

Giles Brad A 28/Jul/2022 Functional Approval

15:52:08

Viewed/Printed: 25 October 2022 3:9:31 PM **Confidential GDMS-D2 Copy-Use per procedure** SOP-000182552 Rev 2