An annual product review (APR) should be conducted for every commercial product in pharmaceutical industry. The objective of this review is to:
- verify the compliance with marketing authorisations,
- verify the consistency of the manufacturing process,
- determine the need for re-validation of existing processes
- assess the trends,
- determine the needs for changes in specifications,
- identify product or process improvements.
APR Relationship to the Quality System
- Compliance to Marketing Authorisation
- Specifications and Controls
- Product Risk Management
- CAPA and Improvement
- Validation, Re-validation and VMP (Validation Master Plan)
SOP for Annual Product Review (APR)
Table of Contents
- Scope and Objectives
- Responsibilities for Reviews
- Product Grouping Strategy
- Product Related Reviews
- Modular (non-product specific) Reviews
- APR Summary Reports and Conclusions
- Risk Assessment and Re-validation Programs
Scope and Objectives
1. Applied separately to each product, or product groups, annually. Grouping shall be justified.
2. If the number of batches manufactured in one year is less than 10 then the APR shall be performed on the last 10 batches, up to a maximum 3 year period.
- For example if 15 batches are manufactured over the last 3 years, chose the
latest 10 batches, but if only 8 batches were manufactured over the last 3
years review the 8 batches.
3. The APR should also include a comparison to the previous year(s) review report, to assess year to year consistency.
Responsibilities for Reviews
1. Team Based Reviews.
2. Head of Quality resposible for overall co-ordination, review scheduling and management:
- Ensuring that the APR is completed on time.
- Overseeing the applicable processes listed in the SOP
- Organising contract manufacturing partners.
- Ensuring investigations when adverse trends observed.
- Reviewing and approving the APR Summary Report:
- raising a change record and agreeing the recommended changes.
- Ensuring commitments for changes and improvements are tracked and completed through the CAPA record.
Product Grouping Strategy
- Common dose forms (sterile, orals solutions, oral powders etc)
- Common container closure formats – different container sizes may be grouped eg 20mL and 25ml of the same presentation.
- Different strengths may be grouped if they are in the same container closure system eg 50mg/100mL and 100mg/100mL.
- Common APIs within a dose form
- Common processing steps (processing steps should be substantially equivalent)
- Substantially equivalent excipient/ carrier bases (eg oily vs aqueous preparations)
- General rule of thumb: prescription separately, OTC and CM consider grouping
- Can validate groupings when the data is being analysed
Product Related Reviews
- Legal: Market Authorisation & Regulatory Notices
- External: Complaints, Recall Adverse Events & Returns
- Processes: Controls, Changes & Process Validation
- Product: Product Testing, OOS, Failures, Retention Samples and Stability
- Quality Control: Product Specification, Test Methods and Changes
- Events: Product Related CAPAs & Incidents/deviations
- Supply Chain / Suppliers and Raw Materials (APIs and Primary Packaging)
- Technical Agreements and Contract Manufacturers
- Critical Equipment Qualifications, Maintenance Programs
- Critical Services (Water, Steam, Gases, HVACsystems)
- Environmental Monitoring Programs
- Effectiveness of the CAPA system, Failure Investigations and Change Control Programs
APR Summary Report and Conclusion
The APR report may take different forms however each of the 12 sections (Product specific review and Modular review) listed should be included. The APR report shall consist of:
- Cover page that includes the APR title, products covered, and signature(s) of the APR reviewer(s) and approvers.
- APR Subsection/Element Reports that contain or reference all of the data and documented analysis for each element.
- Annual Product Review Summary that contains an integrated analysis of all the APR Subsection/Element Reports and the overall APR rating.
- Reference list of all CAPAs raised as result of the APR summary
- Link APR to ongoing validation program, CAPA and risk management
APR conclusions and rating can be:
- Satisfactory – A risk assessment is not warranted.
- Acceptable – A risk assessment may not be warranted.
- Acceptable with conditions – A risk assessment should be performed.
- Unacceptable – A risk assessment must be performed and notification to regulatory agencies considered as part of mitigation and communication.
- Where a report is rated “Acceptable with Conditions” or “Unacceptable” the report should be forwarded to Executive Management for review
APR Report Approval
The final sign off for each APR Summary Report rests with:
- The QA Manager
- The Regulatory Affairs Manager
- Production/Operations Manager
- Other groups who may be affected by any change