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
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.
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.
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.
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.
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.
The EU Requirements for PQR(4)(x) For new marketing authorisations and variations to marketingauthorisations, 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.
PQR Relationship to the Quality System CAPA and Improvement Compliance to Validation Marketing Re- Authorisation validat ion PQR and VMPSpecifications Product Riskand Controls Management
Six Areas: Product Specific Reviews1.Legal: MarketAuthorisation & Regulatory Notices2.External: Complaints, Recall Adverse Events & Recall3.Processes: Controls, Changes & Process Validation4.Product: Product Testing, OOS, Failures, Retention Samples and Stability5.Quality Control: Product Specification, Test Methods and Changes6.Events: Product Related CAPAs & Incidents/deviations
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
Complaints Recall Adverse Events & Returns Customer complaints Product recall Adverse event profiles Product returns∎ Medical Affairs and QA
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
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
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
Six Areas: Modular Reviews1. Supply Chain / Suppliers and Raw Materials (APIs andPrimary Packaging)2. Technical Agreements3. Critical Equipment Qualifications, MaintenancePrograms4. Critical Services (Water, Steam, Gases, HVACsystems)5. Environmental Monitoring Programs6. Effectiveness of the CAPA system, Failure Investigations and Change Control Programs
Follow Up ActionsFollow-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