STANDARD OPERATING PROCEDURE

Title Handling of Out of Trend (OOT) Result

SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 1 of 14

Effective
Review period 2 Years
Date

Prepared by
Name Designation & Department Signature & Date
T.Arun Prasad Manager - GQM

Reviewed by
Name Designation & Department Signature & Date

Venugopalan P Manager - GQM

Approved by

Name Designation & Department Signature & Date

S. Sri Rama Murty Sr. Director - GQM

GQA001/F01-02
 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 2 of 14

1.0 OBJECTIVE
To lay down a procedure for identification and handling OOT results obtained during
QC testing.

2.0 SCOPE
2.1 This SOP is applicable to all drug substance and drug product manufacturing units of Dr.
Reddy’s Laboratories within India and covers the OOT obtained for variables data from
following category of samples;
• Intermediates, in case of drug substance manufacturing,
• Active Pharmaceutical Ingredients,
• Inprocess, in case of drug product manufacturing,
• Finished products.
2.2 This SOP covers the handling of OOT resulted during;
• Release testing of commercial batches
• Stability evaluation
2.3 This SOP is NOT applicable to ;
• Packaging materials,
• Attribute data,
• Drug products, which are having overages such as Nutraceuticals and other
types which are administered for prophylactic purpose

3.0 RESPONSIBILITY :
3.1 Laboratory analyst: To report the OOT results promptly to laboratory head/designee and
QA head/ designee and log the OOT results.
3.2 Laboratory supervisor: To investigate the reported OOT test results as per procedural
requirements stated in current version of GQA035.
3.3 Laboratory head/designee: To initiate CAPA based on the findings of laboratory
investigation. In co-ordination with QA head/designee, shall be jointly responsible for
implementation and compliance of this procedure.

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 3 of 14

3.4 QA head/designee: In co-ordination with laboratory head/designee shall be jointly

responsible for implementation and compliance of this procedure.
3.5 Designated personnel of site QA: To provide control limits for required variables, post
review of annual product quality review.
Note: In addition to the above responsibilities, unless the context otherwise indicates, the
roles & responsibility set forth in section 3.0 of current version of GQA035 “Handling
OOS results” shall apply to this procedure.

4.0 DEFINITION(S)

4.1 Assignable causes: The underlying special cause, identified (either during laboratory
/manufacturing investigation) based on scientific evidence, which is responsible for
OOT.
4.2 Atypical result: A laboratory test result that is within its specification, but which is
markedly different from values obtained from series of test results, which is considered
to be aberrant/abnormal/irregular and need to be investigated.
4.3 Attribute data: Discrete categorical data that can be counted or classified in some
meaningful way but which cannot be measured. These ‘count’ data may be expressed as
‘PASS/FAIL’ ‘YES/NO’ ‘PRESENCE OF DEFECT/ABSENCE OF DEFECT’
4.4 Control chart – A Graphical method of recording results (obtained by measuring a
continuous variable), in order to distinguish between random causes and assignable
causes of variation in a process. It presents a graphic display of process stability or
instability over time.
4.5 Control limit – Numerical value derived (through control chart) for a process such that
any result obtained beyond that value indicates some change has occurred to the process
and that action should be taken to investigate and/or correct for the change. These limits
are assigned either side of the center line and are designated as Upper control limit (UCL)
and Lower control limit (LCL).
4.6 Out of Trend: In case of release testing of commercial batches, a laboratory test result
which is atypical and indicates that manufacturing process could be out of control.

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GQA001/F01-02
 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 4 of 14

(outside the normal analytical /sampling variation & normal change over the time). In
case of stability evaluation, a laboratory test result that is significantly different and not
in agreement with the results obtained from previous stations. An OOT in stability
sample may provide early indication of a potential OOS result, which may also
necessitate CAPA.
4.7 Random causes: These are the common causes of variation that cannot be precisely
identified and are part of normal variability of the process or testing. Example. Machine
vibration, Temperature fluctuations, etc.
4.8 Variable data: Data which is obtained by measurement (for a specific process:-
manufacturing/testing) and has a definite numerical value. Within the context of this
SOP, variables refers to test results of “Assay, Chromatographic purity, Related
substances, LOD, Water content, Dissolution, Acceptance value for Content Uniformity,
Preservative content, Residual solvents, Microbial limit test which are either included
as part of release and/or shelf life specification”.
Note: In addition to the above terminology, definitions set forth in section 4.0, in current
version of GQA035 “Handling OOS results” shall apply to this procedure.

5.0 ABBREVIATION(S)

API - Active Pharmaceutical Ingredient

APSD - Aerodynamic Particle Size Distribution

CAPA - Corrective Action & Preventive Action

UoD - Uniformity of Dosage units

DDU - Delivered Dose Uniformity

LIMS - Laboratory Information Management System

LoD - Loss on Drying

RoI - Residue on Ignition

TAMC - Total Aerobic Microbial counts

TVC - Total Viable counts

TYMC - Total yeasts and Moulds counts

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GQA001/F01-02
 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 5 of 14

6.0 PROCEDURE
6.1 General requirements : Unless otherwise explicitly stated in this procedure, the
procedural requirements to below mentioned activities shall be followed as per current
version of GQA035 ‘Handling of OOS results’

Detailed approach for Phase I (to identify and rule out any laboratory error) &
for phase II investigation (to identify the assignable cause which has resulted the
OOT, provided there is NO lab error), including the investigation formats for
documenting the investigation findings, Retest plan, including experimental
activities, if any ,

Timelines for investigation & Extension requirements.

Similarly, for investigations related to OOT observed in microbiological parameters,

including their timelines shall be as per current version of GQA036 ‘Investigation of
Microbial failures.

6.2 Identification of OOT result: Upon completion of analysis, the analyst shall evaluate,
whether the ROUNDED OFF result meets criteria for OOT as applicable to the sample type.
6.2.1 During release testing of commercial batches, where control charts are not
established. The obtained result shall be considered as ‘Atypical’, provided the result
meets the criteria mentioned in table l.0
Table 1.0. R E L E A S E T E S T I N G O F C O M M E R C I A L B A T C H E S
TEST IF/FOR CRITERIA TO CONSIDER THE RESULT AS A TYPICAL
Assay / One sided specification
Chromato limits Not applicable.
graphic Specification width < 6
purity Specification width is even Any result, which is > 80 % specification width
and which is > 6
Absolute difference A test result obtained, which is not more than
between the highest or lower limit by absolute value of 1.0 and not less
lowest value from 100 is than upper limit by absolute value of 1.0.
between > 3 to < 5 Illustration: For an product with specification
limit of 96.0 to 105.0% , any value, which is either
< 97.0 or which is > 104.0% shall be considered
as OOT.

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GQA001/F01-02
 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 6 of 14

Table 1.0. R E L E A S E T E S T I N G O F C O M M E R C I A L B A T C H E S
TEST IF/FOR CRITERIA TO CONSIDER THE RESULT AS A TYPICAL
Assay / Absolute differenceA test result obtained, which is not more than
Chromato between the highest or lower limit by absolute value of 2.0 and not less
graphic lowest value from 100 is than upper limit by absolute value of 2.0.
purity >5 Illustration: For an product with specification
limit of 92.5 to 105.0% , any value, which is either
< 94.5 or which is > 103.0% shall be considered
as OOT.
Related All types of Specification Any test result, which is > 80% of the
substances limits. specification limit.
(Known,
Single max,
Total)
Lo D / Where Specification is Any result which is > 90% of the specification
Water only USL < 1.0% limit.
content / is defined Specification is Any result which is > 95% of the specification
R o I/ > 1.0% limit.
S u l p h at e d
Where All limits A test result obtained, which is not more than
ash
both USL lower limit by 10% (including) of the
& LSL are specification width and not less than upper limit
defined by 10% (including) of the specification width.
Illustration: For a product with specification limit
of 3.0 to 6.0%, any value, which is either < 3.3 or
which is > 5.7% shall be considered as OOT.
Residual Specification is < 100ppm Not applicable
solvents Specification limit is > 100 Any result which is > 90% of the specification
ppm and < 1000ppm limit.
Specification limit is > Any result which is > 95% of the specification
1000ppm limit.
TAMC or All type of samples Any result which is > 250 C F U / g
TV C
TYMC All type of samples Any result which is > 50 C F U / g
D i s s o l u t i o All type of samples Results of preliminary (S1/L1,..)Stages, indicates
n or U o D or that it does NOT comply with the pharmacopoeial
DDU requirement.
APSD All type of samples Any result of fine particle dose/mass less than
5µm is > 50% the specification
Note to Table 1.0

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 7 of 14

i. Specification width = Difference between Upper specification limit (USL) and Lower
specification limit (LSL)
ii. If the assay limit is given other than % (such as µg, ppm, etc) convert the limits into %
with reference to label claim and determine whether the converted result (in %) is
‘Atypical’ or not
iii. In case of multiple stage testing, like Dissolution, CU, if the results at any of the
preliminary stages such as Dissolution S1/S2 (for Immediate release ), L1 and L2 (for
Extended release) , A1 and A2 (Acid stage), B1 and B2 (Buffer stage) of Delayed release
; Also stage 1 for CU, indicate that results do not comply with pharmacopoeial
requirement, an OOT investigation shall be conducted. Example. In Dissolution, if one
unit is < Q+5% , at stage I, an OOT investigation shall be conducted and in such cases
subsequent stage can be done parallel.
However, if the results at any stage of testing indicate that the same will not comply as
per monograph or specification limits, the same shall be handled as per GQA035
‘Handling OOS results’.
6.2.2 During release testing of commercial batches, where control charts are available;
Following checks shall be applied to the rounded off result to determine any drift in
trend.
⇒ Check I: Whether the rounded off result is outside the 3σ control limits?
⇒ Check II: Whether 7 consecutive points are either having increasing /decreasing
pattern. ?
The obtained result shall be considered as ‘Out of trend’, if the rounded off result
conforms to any of the above checks.
6.2.3 During stability evaluation: The obtained result shall be considered as ‘Out of trend’,
provided the result meets the criteria mentioned in table 2.0

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 8 of 14

Table 2.0. F O R S T A B I L I T Y E V A L U A T I O N S A M P L E S
TEST CRITERIA TO CONSIDER THE RESULT AS OOT
Assay or • The result at specific time interval is varying with previous interval by
chromatographic − absolute value of 2 (for intermediates & API) ;
purity − absolute value of 4 (for drug products)
• Any result, which is > 80 % specification width.
Related • The result at specific time interval is varying with previous interval by
substances absolute value of 50%
(Known, • Any result which is > 80% of the specification limit.
Single max, EXCEPTION:
Total) − However, if the result is < 50% of the specification limit, the
result shall N O T be taken for OOT comparison with previous
interval
Illustration_1: For an impurity with specification limit of NMT 0.10%;
T1M result =0.02% ; T2M result = 0.05%. The T2M result shall NOT be
considered as OOT, since the T2M result is = 50% of specification limit,
despite there is more than 100% variation from previous interval.
Continuing above, if T3M result = 0.08%, the same shall be considered as
OOT, since the result is = 80% of specification and variation is >50% from
previous interval. However, if the T3 result would be 0.07%, the same shall
NOT be considered as OOT.
Illustration_2: For an impurity with specification limit of NMT 0.20%;
T1M result =0.03%; T2M result = 0.09%. The T2M result shall NOT be
considered as OOT, since the T2Mresult is = 50% of specification limit,
despite there is 200% variation from previous interval. Continuing above,
if T3M result = 0.13%, the value shall NOT be considered as OOT, since
the variation is < 50% from previous interval. However, if the T3result
would be 0.15%, the same shall be considered as OOT.
LoD/RoI • The result at specific time interval is varying with previous interval by
Water content absolute value of 50%.
Sulphated ash EXCEPTION:
− However, if the result is < 50% of the specification limit, the
results shall N O T be taken for OOT comparison with previous
interval
Preservative • The result at specific time interval is varying with previous interval
content by ± 25%
Dissolution • The Σ value at specific time interval is varying with previous interval
by absolute value of 10.
APSD • Any result of fine particle dose/mass less than 5µm is > 50% the
specification

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 9 of 14

6.3 Reporting of OOT: If the observed rounded off result meets the (applicable) criteria as
mentioned above, the analyst shall immediately notify the same to QC head/designee
(group leader/laboratory supervisor) and QA head /designee (AQA personnel) WITHIN
24 HOURS FROM THE TIME OF NOTICE/OCCURRENCE. The laboratory supervisor shall
independently evaluate for presence of OOT and also compare the observed results
against the specification limits, prior to logging of OOT.
6.4 Logging of OOT: Subsequent to reporting, the identified OOT result shall be manually
assigned with unique alphanumeric number by laboratory personnel through a register
‘Log for OOT ’ as given in annexure GQC005/A01
6.4.1 The above manual OOT assignment shall be analytical reference specific and the
numbering nomenclature for manual logging shall contain 4 elements, which are
separated by slash ‘/’ and consists of alphanumeric characters, as explained below.
ELEMENT 1 ELEMENT 2 ELEMENT 3 ELEMENT 4
OOT Z YY XXX
Where,
Element 1 refers to the acronym ‘Out of test’;
Element 2 ‘Z’ refers to unit/function code, which is followed consistently;
Element 3 ‘YY’ refers to last 2 digits of calendar year in which OOT is logged;
Element 4 ‘XXX’ refers to a sequential number starting from 001 with increment
of 1 to a particular unit/function for every calendar year.
Example. The tenth [10th] OOT logged in year 2017 at;
CTO-I shall have unique alphanumeric code as “OOT/CTO-I/17/010”
Central stability cell located in FTO-II shall be “OOT/FTO II-CSC/17/010”
6.4.2 In case, if multiple OOT results are reported within a particular analytical reference
number, the OOT number assigned shall be only once, however the investigation formats
shall be issued to individual test specific, cross referencing the same OOT number with
appropriate remarks.
6.5 Laboratory investigation-Phase-I: The investigation shall be initiated at the earliest
time, after OOT is reported, in order to determine whether any lab error has resulted the
OOT. The designated personnel of lab shall issue a copy of current version of

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 10 of 14

GQA035/F02, to the investigator for initiating laboratory investigation and to document

the investigation findings.
6.5.1 Inferences from preliminary assessment:
OBSERVATION RECOMMENDED ACTION
Errors are NOT obvious Remeasurement as part of initial hypothesis
Errors are clearly evident. Hypothesis to establish the root cause which
Document the obvious errors might resulted for variation during testing.
with objective evidences

6.5.2 Inferences from Re-measurement

OBSERVATION RECOMMENDED ACTION
No assignable cause for Confirm the initially reported result as OOT.
laboratory variation is suspected The OOT information shall be given to
manufacturing [routed through QA] to identify
the assignable cause, which has resulted the
variation.
Assignable cause(s) are Hypothesis testing by simulating the specific
suspected lab error, after due authorization from QA.

6.5.3 Inferences from Hypothesis testing

OBSERVATION RECOMMENDED ACTION
Theory is NOT proved or Confirm the initially reported result as OOT.
Hypothesis testing is The OOT information shall be given to
inconclusive. manufacturing [routed through QA] to identify
the assignable cause, which has resulted the
variation.
Theory is proved (through After rectifying the specific laboratory error,
scientific/experimental means) the investigator shall recommend for retesting
and root cause for OOT result is as per ‘Retest plan’ given in annexure
established GQA035/A04.

6.5.4 Inferences from Retesting

OBSERVATION
All the individual sample
preparations/measurements
complies with specification and
not fall under applicable criteria
mention in 6.2
If any 1 sample preparation
/measurement meets the criteria
Prepared by
RECOMMENDED ACTION
The initial reported result shall be invalidated
(ie) not be considered as OOT and final
reporting shall be as stated in retest plan as per
GQA035/A04.
Confirm the initially reported result as OOT.
The OOT information shall be given to
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GQA001/F01-02
 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 11 of 14

OBSERVATION RECOMMENDED ACTION

mentioned in 6.2 or results of
retesting in NOT within normal
trend, the initial reported result
should be confirmed as OOT.
If any 1 sample preparation
/measurement does NOT meets
specification (ie) OOS
manufacturing [routed through QA] to identify
the assignable cause, which has resulted the
variation.
Shall be handled as per GQA035. The failure
information shall be given to manufacturing
[routed through QA] to identify the aberration,
which has resulted the failure.

6.6 Manufacturing investigation -Phase II: If the laboratory investigation determines that
there no laboratory error (which has resulted for OOT), manufacturing investigation
shall be initiated to identify the assignable cause in manufacturing process which has
resulted the OOT. The designated personnel of manufacturing shall issue a copy of
current version of GQA035/F03, to the investigator for initiating manufacturing
investigation and to document the investigation findings.
6.6.1 Inferences from manufacturing investigation:
OBSERVATION RECOMMENDED ACTION
If assignable cause which has The initial reported OOT result shall be
resulted for variation is evident considered as valid. Subsequent to which ;
• Batch disposition shall be taken by QA, based on
review of additional relevant data such as
stability, validation etc.
• CAPA initiation, if necessitated.
If probable causes are suspected Hypothesis studies , after authorization from
which has resulted for variation QA
is evident
6.6.2 Inferences from Hypothesis studies
OBSERVATION RECOMMENDED ACTION
Root cause for manufacturing The initial reported OOT result shall be
variation is established considered as valid. Subsequent to which ;
• Batch disposition shall be taken by QA, based on
review of additional relevant data such as
stability, validation etc.
• CAPA initiation, if necessitated.

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 12 of 14

6.6.3 Inferences from Retesting (provided hypothesis studies are inconclusive & QA
authorization for retesting)
OBSERVATION RECOMMENDED ACTION
All individual outcomes of retest The initial reported OOT result shall be
passes and none of them fall considered as invalid. Subsequent to which ;
under applicable criteria mention
• Batch disposition shall be taken by QA, based on
in 6.2 review of additional relevant data such as
stability, validation etc.
• CAPA initiation, if necessitated.
Any one of the retest outcomes The initial reported OOT result shall be
meets applicable criteria considered as valid. Subsequent to which ;
mention in 6.2 • Batch disposition shall be taken by QA, based on
review of additional relevant data such as
stability, validation etc.
CAPA initiation, if necessitated.
Additionally, the process shall be monitored for
‘n’ number batches or ‘x’ time period as
applicable, based on which CAPA shall be
determined.
6.6.4 The OOT subjected batch shall be on hold, until the decision of final disposition has
been taken by QA head/designee.
6.6.5 Impact assessment shall be performed to ascertain the extent of identified assignable
cause to;
• Other batches of same product and/or
• Batches of different product
Whenever additional batches are considered for investigation, rationale for selection of
batches should be clearly recorded and shall be part of investigation report.
6.7 Dealing with OOT results obtained during stability evaluation;
6.7.1 As part of document review following points shall be verified but not limited to:
• Time delay in stability initiation from the day of manufacturing.
• Review of initial analytical data.
• Change in source of input materials, if any.
6.7.2 In case, if investigation at 1st instance for a specific sample, condition, pack type has
determined that, OOT is due to inherent behavior/nature of product (ie) evident of
stability failure, for any OOT reported at subsequent instance(s), the investigation shall

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 13 of 14

be restricted only to lab investigation (if necessitated through format, as per

GQA035/F02) to ascertain the presence of any lab error and cross reference of earlier
concluded investigation [at 1st instance] shall be included. In such cases (ie) for OOS
reported as 2nd instance [to the same specific sample, condition, pack type] the logging
of OOT may be waived off.
6.7.3 In case of new products, QA shall refer the investigation to process development.
6.7.4 In cases, where OOT result has been confirmed, an assessment of impact on product
quality shall be done which shall include but shall not only restricted to ;
• If there is a likelihood of failure of the OOT batch or other batches in the
market during their shelf life based on product historical stability data.
• If cause of OOT was due to change in process then impact on other batches
manufactured using same process
• If cause of OOT was due to equipment /instrument error, then impact on
same product/other products manufactured or analyzed using the same
equipment/instrument.
6.7.5 To assess the impact on other batches, samples kept on stability, control samples or
market samples shall be used for analysis. Such assessment shall be clearly recorded and
shall be part of investigation report.

6.8 Assessment or Trend & evaluation of reported OOT: Review of OOT results for
commercial batches shall be done on a quarterly basis as part of management review.
Additionally as annual basis (as part of Product Quality Review/Annual Product Quality
review), the review shall be performed. The review shall include classifying the OOT
results based on root causes (such as analyst error, instrument error, equipment error,
input material, etc) and repeat OOT’s.

6.9 Reporting of OOT failure to Regulatory authority/QP/Customer:

If any OOT is confirmed on stability samples of commercial batches, the information
shall be given to respective QP/ regulatory authority/Customer as appropriate.

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 STANDARD OPERATING PROCEDURE
Title Handling of Out of Trend (OOT) Result
SOP No. GQC005-03 Unit Global
Department Quality Control Page No. 14 of 14

6.10 Development of OOT limits;

6.10.1 Control charts shall be derived as per the recommendations stated in guidance GQD002
“Statistical Analysis”.
6.10.2 The control limits shall be established by designated personnel of QA, subsequent to
approval of Annual Product Quality Review report. Once established, the control limits
shall NOT be re-evaluated, unless there is change in process or change in testing method.
6.10.3 The above, established control limits shall be communicated by designated personnel of
QA to laboratory personnel through the format ‘OOT limits’ as per annexure
GQC005/A02
6.10.4 In case of drug product manufacturing locations, the control limits derived by the API
manufacturer shall be considered, rather than establishing in-house control limits for
API.

7.0 REFERENCE(S)
7.1 In-house
7.2 GQA035-Handling OOS results.

8.0 ANNEXURE
Annexure No. Title of the Annexure Form No.
GQC005/A01 Format for ‘Log for OOT’ GQC005/F02
GQC005/A02 Format for ‘OOT limits’ GQC005/F01
GQC005/A03 Flow chart for Handling OOT results ---NA---
GQC005/A04 Handling of OOT result through LIMS ---NA---

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 Annexure No. GQC005/A01
Format for “Log for OOT”

Unit: Global Department: Quality Control Page: 1 of 1

Global Quality
<Unit> LOG FOR OOT

Page: 1 of x
DATE OF OOT. PRODUCT/ BATCH TEST SPEC. INITIAL ENTERED BY FINAL ROOT STATUS OF ENTERED BY
REPORTING # STAGE NO PARAMETER LIMIT RESULT SIGN & DATE RESULT CAUSE THE BATCH SIGN & DATE

GQC005/F02-01
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 Annexure No. GQC005/A02
Format for OOT limits

Unit: Global Department: Quality Control Page: 1 of 1

Global Quality OOT LIMITS

(RAWMATERIALS/INPROCESS/FINISHED PRODUCTS)
Page: 1 of 1

MATERIAL / PRODUCT NAME

MATERIAL / PRODUCT CODE
SPECIFICATION NUMBER
APR /PQR .NO

S.NO TEST NAME OOT LIMIT

UPPER CONTROL LIMIT LOWER CONTROL LIMIT

REMARKS:

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 Annexure No. GQA001/A05

Flow chart for Handling OOT results

Unit: Global Department: Quality Control Page: 1 of 2

QC testing OOT Logging of OOT

result
Phase I: Laboratory investigation to identify lab error

Preliminary assessment, Document review & Discussion Rectify formula &

reapply; invalidate the
Calculation /Transcription/ OOT result
Integration /processing error
Any obvious Close investigation
NO error? YES
Evidence or suspicion related to
Re-Measurement after due sample integrity/sampling error
authorization from QA
Re-Sampling after due
authorization from QA
Request for Hypothesis: Authorization
NO YES
Any assignable from QA head/designee
cause suspected?
Hypothesis testing Generate
CA &PA
YES
Root cause
established?
NO
Impact assessment
Confirm the reported
result as OOT
Request for Retesting: Authorization
Outsourced from QA head/designee
materials
Products Retesting
Processed in site Information to vendor by QA
through SCM & VQM
All the individual YES
Joint analysis outcomes of
NO
Retest passes?
Investigation
report from vendor
Invalidate the OOT result with appropriate
Impact assessment of other comments, reason for initial failure & final
materials supplied by vendor reporting shall be as per GQA035/A04

Batch disposition by QA Close investigation

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 Annexure No. GQA001/A05

Flow chart for Handling OOT results

Unit: Global Department: Quality Control Page: 2 of 2

Phase II: Full scale investigation to identify manufacturing aberration

Probable causes
are identified Root cause
NO
clearly evident? YES
Request for Hypothesis: Authorization
from QA head/designee Generate
CA &PA
Hypothesis studies

NO Root cause for YES Impact assessment of other

manufacturing
batches and/or products
failure established?

Failure related to parameters, which involves Batch disposition by QA

measurement of variability within samples such
as Dissolution, UoD, BU,etc
Close investigation
Failure related to parameters, which
involves measurement as a composite such
such as Assay, Related substances,etc

Request for Retesting after verification:

Authorization from QA head/designee

Re-Sampling after due authorization from QA

Retesting

Batch disposition All the individual

by QA Evaluation of
outcomes of
retest outcomes
NO Retest passes?

Monitoring of subsequent batches

after implementation of action items Monitoring indicates variation has been
eliminated/reduced: The probable causes
identified shall be confirmed as reasons for
Close investigation with probable causes, variation in addendum report.
along with action plans to eliminate.

Prepared by Reviewed by Approved by

Sign. & Date

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