Acme Formulation Pvt Ltd, Nalagarh (H.P.

)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 1 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

1.0 PURPOSE
To lay down a procedure for handling of Out of Trend with respect to analytical result
process parameter and environment monitoring.
2.0 SCOPE
This SOP is applicable for handling of out of trend (within specification) results observed
in Hormone Block at Acme Formulation Pvt. Ltd.
3.0 RESPONSIBILITY
3.1 Officer/Executive (User Department) shall be responsible for investigation of OOT
and communication to respective HOD and QA.
3.2 HOD of user department and QA shall be responsible for investigation and
identification of root cause and proposal of CAPA.
3.3 Head QA/Designee shall be responsible for review of investigation and evaluation of
CAPA.
4.0 ACCOUNTABILITY
4.1 Head-QC and Head-QA shall be accountable for compliance of this SOP.
5.0 PROCEDURE
5.1 Criteria for OOT Result
Following criteria shall be used to consider result as out of trend after consultation
with QA.
5.1.1 If the critical parameter analyzed shows an abnormal result in comparison to
the other unit (of different batches) of the same strength`.
5.1.2 If the critical parameter analyzed shows an abnormal result in comparison to
the previous station sample of the same storage condition. (Stability sample
results)
5.1.3 Trend shall be prepared for minimum 10 batches and determine the UCL &
LCL on the basis of trend. APQR trends shall be followed to get the OOT
limits based on 2 sigma and 3 sigma approaches.
5.1.4 If finished assay release specification limit is 90-110, OOT shall be raised in
case observed results values <92 or >108.
5.1.5 If finished assay release specification limit is 95-105, observed results within
95-105 shall be reported as such. QA can take decision to investigate for any
uneven results based on product trend data and behavior.

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202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01

 Acme Formulation Pvt Ltd, Nalagarh (H.P.)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 2 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

5.1.6 In cases of blend assay where release specification limit is 95-105, if

composite assay results found out of limit but within 90-110, then blend
uniformity shall be performed. If BU results and RSD found well within the
limit and average within 95-105 then average of BU shall be reported as assay.
OOS shall be raised if BU average shall not be within 95-105
5.1.7 In case of finished product testing where average of content uniformity shall
be reported as assay. If observed CU results average shall not be within 95-
105, then proceed for L2 stage where next 20 tablets will be analyzed and
average of 30 tablets shall be within release specification limit 95-105. OOS
shall be raised if CU average shall not be within 95-105
5.1.8 OOT shall be raised if Dissolution shall go for S3 stage.
5.1.9 In case of Stability assay, OOT shall be raised if there is a ±5% variation from
initial results.
5.1.10 In case of related substance test, for impurities NMT 0.5% and NMT 1.0%,
OOT shall be raised if an impurity crosses 80% of the specification limit or
based on historical trend data as applicable.
5.1.11 OOT shall not be raised for impurities having specification limit below 0.5%
5.1.12 OOT shall not be raised for established trends (in case of stability study)
5.1.13 The result shall be declared as OOT only after consultation with Head QA.
5.1.14 Only chemical parameter shall be treated as critical.
5.2 Handling of OOT Result
5.2.1 Whenever any OOT result observed, same shall be recorded as per (Format
No. HA028/F01) & further processing shall be done as per flow mentioned in
format number (HA028/F04).
5.2.2 Each OOT shall be investigated as per (Format No. HA028/F02) and SOP on
Root cause Analysis Tools (SOP/HA/087) if required.
5.2.3 Investigation team shall initiate investigation and final approval to be done by
Head QA/Designee.
5.2.4 Each OOT result shall be assigned a unique number as OOT/XX/YYY, e.g.
first OOT of year 2019 shall be assigned as OOT/19/001
Where:
 OOT stands for Out of Trend
 The 4th character / is a forwarding slash

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202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01

 Acme Formulation Pvt Ltd, Nalagarh (H.P.)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 3 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

 XX will be two digits of current year

 The 7th character / is a forwarding slash
 Last three numeric characters shall be the sequential no. for OOT (i.e.
001,002,003 and so on).
5.2.5 QC team shall refer SOP on Out of Specification results (SOP/HA/018) to
perform Phase-I investigation.
5.2.6 If the investigation reveals an assignable cause, then the analysis shall be
repeated in duplicate and the mean value shall be considered for reporting.
5.2.7 If the cause is not assigned, then an experimental plan will be designed in
consultation with QA and manufacturing investigation shall be carried out
accordingly.
5.2.8 The reporting/corrective action shall be carried out based on the outcome of
the above study.
5.2.9 An OOT investigation shall be completed within 30 working days.
5.1.1 In case the investigation exceeds more than 30 days then interim report shall
be generated by QC Head /designee and extension shall be taken for
investigation after authorization by Quality Assurance Head/Designee.
5.1.2 Wherever applicable Quality Assurance head shall notify the OOT results to
Head of RA, Manufacturing Head/customer as defined in respective
agreement.
5.3 Trend of OOT
5.3.1 OOT trend shall be prepared and reviewed on half yearly basis.
5.3.2 Content of Trend to be covered as below:
5.3.2.1 Objective
5.3.2.2 Scope
5.3.2.3 Total Number of OOT during the review period with closure status.
5.3.2.4 Month wise review of OOT during the review period.
5.3.2.5 Review of OOT based on the classification i.e. analytical
error/Manufacturing error.
5.3.2.6 Categorization of Analytical error
(a) Dilution error

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202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01

 Acme Formulation Pvt Ltd, Nalagarh (H.P.)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 4 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

(b) Sample preparation error

(c) Procedural error
(d) Contamination
(e) Procedural non compliance
(f) Instrument performance error
5.3.2.7 Manufacturing error
(a) Procedural non compliance
(b) Procedure not follow
(c) Raw Material issue
5.3.2.8 Review of OOT for closure status with open/closed beyond time line
with justification.
5.3.2.9 CAPA review for OOT.
5.3.2.10 Review of Repeated OOT.
5.3.2.11 CAPA review status for repeated OOT.
5.3.2.12 Comparison with previous trend for OOT.
5.3.2.13 Department and section/stage wise review of OOT.
5.3.2.14 Review of Root Cause wise OOT
5.3.2.15 Effective analysis tools shall be used for trend analysis (pie chart, Bar
chart, Pareto analysis, any other statistically shall be used) during
trend analysis.
6.0 PRECAUTION
NA
7.0 RELATED DOCUMENTS
7.1 SOP on Out of Specification (OOS) Result
8.0 LIST OF FORMATS

S.
Title of Format Format Number
No.
8.1 Log book for out of trend result HA028/F01

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202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01

 Acme Formulation Pvt Ltd, Nalagarh (H.P.)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 5 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

8.2 Out of trend test result investigation form HA028/F02

8.3 Trend Analysis Discontinued

8.4 Flow chart for OOT test result HA028/F04

9.0 REFERENCES
9.1 ICH guidelines handling OOT.

10.0 ABBREVIATIONS

Abbreviation Description

ICH International conference on harmonization

LOD Loss on drying

OOT Out of trend

RSD Relative standard deviation

RS Related substances

LCL Lower Control Limit

UCL Upper Control Limit

HA Hormone Block Quality Assurance

SOP Standard operating procedure

°C Degree Celsius

11.0 REVISION HISTORY

Revision No. Effective Date Change Control No. Reason of revision
02 09 Jan 2018 NA Scheduled Revision
The format of SOP has been revised to in line
E0 23/04/2019 HB/CC/HA/18/319
with EDCS software.

Prepared By Checked By Approved By

202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01

 Acme Formulation Pvt Ltd, Nalagarh (H.P.)
Standard Operating Procedure
Originating Department: Quality Assurance
Title: SOP on Out of Trend Results
SOP No.: SOP/HA/028 Version No.: E2 Page 6 of 6
Effective Date: 15/03/21 Review Date: 15/03/23

HB/CC/HA/20/202 Procedure and Attachments of the SOP has been

E1 08/10/2020
reframed.
1. Responsibility for QA and QC has been
updated.
2. Criterion for OOT Results has been
elaborated.
3. Procedure for Handling of OOT Results has
been elaborated.
4. Procedure for Trending of OOT has been
E2 15/03/21 HB/CC/HA/21/018
updated.
5. Format of Out of trend test result investigation
form (HA028/F02) has been reframed.
6. Flow chart for OOT test result (HA028/F04)
has been reframed.
7. Format for Trend Analysis (HA028/F03) has
been discontinued.

Prepared By Checked By Approved By

202589 on 12/03/21 17:28:52 202432 on 12/03/21 17:39:34 201044 on 13/03/21 10:03:20

Format No. HA001/F01