2. The Overview
• What is the Product Quality Review?
• Objectives
• EU GMP requirements
• PQR Relationship to the Quality System
• Six Areas: Product Specific Reviews
• Six Areas: Modular Reviews
• Follow Up Actions
3. Product Quality Review?
Product Quality Review is regular periodic or rolling quality reviews of
all licensed medicinal products, including export only
products, which are conducted with the objective of verifying
the consistency of the existing process, the appropriateness
of current specifications for both starting materials and
finished product to highlight any trends and to identify
product and process improvements.
The Product Quality review (PQR) is an effective quality improvement
tool to enhance the consistency of the process and the
overall quality of the product. The PQR will capture a broader
view of product data, capturing trends and will help
determine the need for revalidation and changes, if any.
4. Objectives
• Determine the need to make changes to manufacturing
processes, process controls, in-process tests or product
specifications
• Verify compliance with marketing authorisations
• Verify the consistency of manufacturing processes
• Determine the need for re-validation of existing
processes
• Identify product or process improvements
• Identify any adverse trends and the need to take
corrective and preventive action
• Determine the appropriateness of starting material and
product specifications.
5. The EU Requirements for PQR
(1)
• EU Guidelines to Good Manufacturing
Practice ; Medicinal Products for Human
and Veterinary Use ; Part I ; Chapter 1
Quality Management (issued on 31
January 2013)
Product Quality Review
1.10 Regular periodic or rolling quality reviews of all authorised medicinal
products, including export only products, should be conducted
with the objective of verifying the consistency of the existing
process, the appropriateness of current specifications for both
starting materials and finished product, to highlight any trends
and to identify product and process improvements.
6. The EU Requirements for PQR
(2)
• Such reviews 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 new sources and in particular the
review of supply chain traceability of active substances.
(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.
7. The EU Requirements for PQR
(3)
(v) A review of all changes carried out to the processes or analytical
methods.
(vi) A review of Marketing Authorisation variations submitted, granted
or 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.
8. The EU Requirements for PQR
(4)
(x) For new marketing authorisations and variations to marketing
authorisations, 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.
9. PQR Relationship to the Quality System
CAPA and
Improvement
Compliance to Validation
Marketing Re-
Authorisation validat
ion
PQR and VMP
Specifications Product Risk
and Controls Management
10. Six Areas: Product Specific Reviews
1.Legal: MarketAuthorisation & Regulatory Notices
2.External: Complaints, Recall Adverse Events &
Recall
3.Processes: Controls, Changes & Process Validation
4.Product: Product Testing, OOS, Failures, Retention
Samples and Stability
5.Quality Control: Product Specification, Test Methods
and Changes
6.Events: Product Related CAPAs &
Incidents/deviations
11. Market Authorisation & Regulatory
Notices
Marketing Authorisation and Post
Marketing Commitments
Regulatory Agency Inspections (product
related
observations and commitments)
Regulatory Agency Product Notices
Recalls / Marketplace Alerts / Adverse
Events
∎
Regulatory Affairs and QA
13. Process Controls,
Changes & Process Validation
Batch Record Review including in-process
controls
Rework/Reprocessing/ Rejects
Yield, Deviations and Product
Investigations
Process Validation Review
Product / Process related changes
∎
Production and QA/Validation
14. Laboratory Product Testing
Quality Control Testing Review results –
include OOS events and non-
conformances)
Finished Product Specification Review
Test Method Validations and Laboratory
Changes
Stability Programs
Retention Samples
∎
QC and QA
15. Product Related CAPAs & Incidents
Effectiveness of corrective actions – close
outs
Follow up from previous APR reports
Significant product related deviations and
incidents
Internal audits (product related
observations)
∎
Production and QA
16. Six Areas: Modular Reviews
1. Supply Chain / Suppliers and Raw Materials (APIs and
Primary Packaging)
2. Technical Agreements
3. Critical Equipment Qualifications, Maintenance
Programs
4. Critical Services (Water, Steam, Gases, HVAC
systems)
5. Environmental Monitoring Programs
6. Effectiveness of the CAPA system, Failure Investigations and
Change Control Programs
17. Follow Up Actions
Follow-up actions may be included but are not limited to:
Product process improvement
Formulation improvement
Analytical method improvements
In-process or final product specification
review
Revalidation
Product recall or withdrawal
Change of RM/PM
