1.

Procedure

1.1 Regulatory Requirements

Step Instruction
1 PQRs should normally be conducted and documented annually, taking into account
previous reviews, and should include at least:
i. A review of starting materials including packaging materials used in the product,
especially those from news sources.
ii. A review of critical in-process controls and finished product results.
iii. A review of all batches that failed to meet established specification(s) and their
investigation.
iv. A review of all significant deviations or non-conformances, their related
investigations, and the effectiveness of resultant corrective and preventive actions
taken.
v. A review of all changes carried out to the processes or analytical methods.
vi. A review of Marketing Authorization variations submitted/granted/ refused,
including those for third country (export only) dossiers.
vii. A review of the results of the stability monitoring programme and any adverse
trends.
viii. A review of all quality-related returns, complaints and recalls and the
investigations performed at the time.
ix. A review of adequacy of any other previous product process or equipment
corrective actions.
x. For new marketing authorizations and variations to marketing authorizations, a
review of post-marketing commitments.
xi. The qualification status of relevant equipment and utilities, e.g. HVAC, water,
compressed gases, etc.
xii. A review of any contractual arrangements as defined in Chapter 7 to ensure that
they are up to date.
2 The regulatory requirements have been transferred into a PQR Elements Matrix (section
1.5) which should be followed as guidance when conducting analysis for PQRs.
1.2 Frequency PQRs

Step Instruction
1 Typically PQR reviews are to be conducted annually.
2 In justified cases, the annual period may be widened. Widened frequencies must be
justified and documented per product involved.
3 Where 2 or less batches have been manufactured in the year a PQR review shall be
conducted every 2 years.

1.3 Grouping of PQRs

Ste Instruction
p
1 PQRs of the company are grouped based on dosage form (liquids are separate from
solids). Grouping follows the WI for Grouping of PQR (WI No. ????).
2 If this approach is adopted, the justification for grouping must be documented and form
part of the PQR report.

1.4 Batches to be Considered

Step Instruction
1 Every batch of commercial product which has been dispositioned in the period covered by
the PQR should be taken in consideration
1.5 PQR Elements Matrix
Step Instruction
1 Used the following PQR Elements Matrix as a guide when conducting analysis for PQRs to
determine scope pf analysis against PIC/S requirements.
PQR Element PIC/S Requirement
1. Starting Materials A review of starting
materials including
packaging materials used
in the product, especially
those from new sources.
2. Process & A review of critical in-
Product Results process controls and
Review finished product results.
3. Deviations & Non- A review of all batches that
Conformances failed to meet established
specification(s) and their
investigation.
A review of all significant
deviations or non-
conformances, their related
investigations, and the
effectiveness of resultant
corrective and preventative
actions taken.
Analysis
a) Review starting materials used in bulk
manufacture, especially those from new
sources.
b) Review starting material used in
packing activity,especially from those
new sources
a) Review critical in-process controls in
bulk manufacture.
b) Review finished product results (QC
Testing).
c) Review critical in-process controls in
packing.
a) Review of all bulk batches that failed
to meet established specifications and
their investigations.
b) Review of all packed batches that
failed to meet established.
c) Review of all significant deviations or
non-conformances, their related
investigations, and the effectiveness
of resultant corrective and
preventative action taking regarding
bulk manufacture.
d) Review of all significant deviations or
non-conformances, their related
investigations, and the effectiveness
of resultant corrective and
preventative actions taken regarding
testing.
e) Review of all significant deviations or
non-conformances, their related
investigations, and the effectiveness
of resultant corrective and
preventative action taken regarding
packing activities.
 PQR Element
4. Process Product Change
Controls
5. Stability Program
6. Complaints and Recalls
7. Corrective Actions
8. Marketing Authorization
PIC/S Requirement
A review of all changes carried
out to the processes or analytical
methods.
A review of the results of the
stability monitoring programme
and any adverse trends.
A review of all quality-related
returns, complaints and recalls
and the investigations performed
at the time.
A review of adequacy or any other
previous product process or
equipment corrective actions.
A review of Marketing
Authorization variations
submitted/granted/ refused,
including those for third country
(export only) dossiers.
For new marketing authorizations
and variations to marketing
authorizations, a review of post-
marketing commitments.
Analysis
a) Review of all changes carried out to
the bulk manufacturing process.
b) Review of all changes carried out to
analytical (and other testing)
methods.
c) Review of all changes carried out to
the processes involved in the
packing activity.
a) Review the results of the initial long
term stability of the bulk product
monitoring program and any
adverse trends.
b) Review the results of the initial long
term stability of the market product
monitoring program and any
adverse trends.
c) Review the results of the on-going
stability of the market product
monitoring program and any
adverse trends.
a) Review all quality-related returns,
complaints and recalls and the
investigations performed at the time.
a) Review the adequacy of any
previous product process or
equipment corrective actions
relating to manufacture of the bulk
product.
b) Review the adequacy of any
previous product process or
equipment corrective actions
relating to packing of the market
product.
a) Review the Marketing Authorization
variations submitted/granted/
refused, including those for third
country (export only) dossiers.
b) Review post marketing commitments
to new marketing authorizations and
variations to marketing
authorizations.
9. Equipment & Utilities The qualification status of relevant a) Review the qualification status of
Qualification equipment and utilities, e.g.
HVAC, water, compressed
gasses, etc.
10. Agreement/Contract A review of any contractual
arrangements as defined in
Chapter 7 to ensure that they are
up to date.
relevant equipment and utilities, e.g.
HVAC, water, compressed gasses,
etc. relating to manufactured of the
bulk product.
b) Review the qualification status of
relevant equipment and utilities, e.g.
HVAC, water, compressed gasses,
etc. relating to packing of the
market product.
Note: Qualification of equipment
and utilities can be reviewed as part
of the Validation Master Plan
schedule and not for each Product
Quality Review.
a) Review any contractual
arrangements relating to
manufactured of the bulk product
as defined in Chapter 7 (of the code)
to ensure that they are up to date.
b) Review any contractual
arrangements relating to
manufacture of the market
product as defined in Chapter 7 (of
the code) to ensure that they are up
to date.
 1.6 Methodology for Analysis of Data
Step Instruction
1 Used the following table as a guide when conducting analysis for PQRs to identify
methodology and tools for use against each PQR element to produce the deliverables.
2 For guidance on SPC Tools, refer to SOP_2201_QS, Use of Statistical Techniques and
Methodology.
PQR Element Methodology
1. Starting Materials The review should cover critical materials
and therein specifications which mainly
determine the quality of the material.
The assessment should address aberrant
analytical results such as confirmed OOS
results and trends highlighting batches
from new sources (new suppliers or new
manufacturing sites), changed production
processes and/or changed specifications.
2. Process & Product The review should cover those in process
Results Review control and finished product results which
mainly determine the quality of the
manufacturing process and of the finished
product.
The assessment should address OOS
results and trends for finished and bulk
product as well as deviations from critical
IPC limits.
3. Deviations & Non- All significant deviation should be
Conformances evaluated for re-occurrence.
Tools/Deliverable
Trending of critical quality
attributes
Use of SPC tools such as:
 Control charts
 I-MR and X bar charts
Compare with previous year
PQRs to identify any negative
trend developing.
Review incoming inspection
reject rate and corrective action.
Trending of critical quality
attributes and critical process
parameters. Include yields.
Use of SPC tools such as:
 Control charts
 I-MR and X bar charts
 Process Capability
 Cp and Cpk measures
Corrective action should be
provided for out of control data
points in control charts.
Cpk should be used ti determine
whether the process is capable.
If Cpk<1.33, corrective action
shall be provided.
Root cause analysis for failures.
Pareto charts/analysis.
Analysis to identify developing
trends.
Compare with previous year
PQRs to identify any negative
trend developing.
Root cause analysis for failures.
Pareto charts/analysis.
 PQR Element Methodology
4. Process & Product Changes which have been implemented
Change Controls should be listed.
5. Stability Program The PQR should summarize the result of
the stability monitoring programme.
The PQR should refer to events such as
OOS results or significant atypical trends
and address actions which have been
taken based on item.
6. Complaints & Recalls Apart from investigations, the review
should assess the effectiveness of
corrective and preventive actions taken.
7. Corrective Actions The effectiveness of any corrective or
preventive action of the previous PQR
period should be addressed.
8. Marketing Change requests which have been
Authorization initiated and approved should be listed
and their status reported.
Examples for post-marketing
commitments may be commitments
concerning the product stability or
commitments concerning any measures
to be implemented in a given time period.
9. Equipment & Utilities Equipment and utilities should be
Qualification assessed concerning their qualification
taking into consideration changes, log
book entries, CAPA relevant occurrence
and similar.
Include environmental monitoring results.
These assessments should be
referenced in the PQR.
10. Agreement/Contract Review contracts and quality assurance
agreements to ensure they are up to date
and determine status.
Tools/Deliverable
Table Status of changes.
Review impact on Marketing
Authorization.
Trending of critical quality
attributes
Use of SPC tools such as:
 Control charts
 I-MR and X bar charts
Compare with previous year
PQRs to identify any negative
trend developing.
Root cause analysis for
investigations.
Pareto charts/analysis.
Provide update status.
Provide summary explanation for
variations, regulatory notices,
recommended actions.
Analysis on failure or
interruptions and corrective
actions.
Root cause analysis for
investigations.
Pareto charts/analysis.
Provide update status.
1.7 PQR Corrective Actions
Step Instruction
1 The manufacturer (XXX) and marketing authorization holder (XXX) evaluates the results of
the PQR reviews and an assessment is made of whether corrective and preventative
action or any revalidation should be undertaken.
2 Reasons for such corrective actions are documented as recommendations and form part of
the PQR report.
3 Agreed corrective and preventative actions are managed via SOP_1701_QS- Corrective
and Preventive Action. Priority is given to these actions (by flagging) to ensure they are
completed in a timely and effective manner.
4 SOP_1701_QS- Corrective and Preventive Action is used as a tool for the ongoing
management, tracking and review of these actions.
5 The effectiveness of AOP_1701_QS- Corrective and Preventive Action is verified during
self-inspection, OP_2401_QS- Internal and External Audits.

1.8 Documentation of PQRs

Step Instruction
1 PQRs are documented in a PQR report encompassing the PQR elements as defined in the
PQR Elements Matrix (section 1.5).
2 The PQR Report is based on an approved template and includes the following sections:
PQR Summary: All data is evaluated as a whole and a summary statement is prepared
and serves to provide an overview of any key observations made.
PQR Recommendations or corrective action: A listing of recommendations or corrective
actions resulting from the PQR defined.
PQR Conclusions: Conclusions regarding product and/or process are listed. Conclusions
from the data review are classified as follows:
 Process in control: indicates there is no deviation observed within the data
presented and confirms that the process continues to function and its validated
status is maintained.
 Actions are recommended: indicates recommended actions should be
considered although validated status is still maintained.
 Corrective actions required: indicates immediate corrective actions are required as
the validated status is no longer maintained. Marketing authorization status needs to
be evaluated for possible withdrawal after assessing the risk. Update the CAPA
system for inclusion of proposed corrective actions for proper follow up.
3 The PQR administrator shall prepare the PQR summary, list out all the corrective actions
and/or recommendations and give the overall conclusion.
4 The PQR administrator shall submit the PQR Report for approval by the PQR Subject
Matter Experts and Quality Manager.
Step Instruction
5 The PQR Administrator will submit the approved report to the General Manager for final
approval.
6 The approved PQR report is to be filed and maintained by the PQR Administrator.
All outstanding action items shall be followed up and closed and managed via the CAPA
System.
Refer SOP_1701_QS – Corrective and Preventive Action.
7 The authorized person responsible for final batch certification (XXX) together with the
marketing authorization holder (XXX) ensures that the PQR is performed in a timely
manner and is accurate.
8 Where the marketing authorization holder is not the manufacturer (eg. Contract
manufacturing where XXX is the Contract Acceptor), technical agreements are in place
between the various parties that defines their respective responsibilities in producing the
documented PQR.
REFER SOP_401_QS, Technical Terms of Supply.

2. Training

The following must all be competent in the SOP:

 Quality Manager
 Production Manager

The following must all be aware of this SOP:

 General Manager

3. References and Related Documents

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3
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5