Department | Quality Management | Document no | QMS-060 | ||
Title | Annual Product Review | ||||
Prepared by: | Date: | Supersedes: | |||
Checked by: | Date: | Date Issued: | |||
Approved by: | Date: | Review Date: | |||
Document Owner
Quality Assurance Manager
Affected Parties
All Quality Assurance, Technical Service, Laboratory and operation’s colleagues
Purpose
This procedure provides a guideline to annual product review which is required to be performed for each product produced for the commercial market to evaluate data, trends and to identify any preventative or corrective action that would lead to product quality improvements and report them to management.
Scope
An APR will be required for all products manufactured or packed. Contract manufacturers should have a comparable system of product review and this will be checked during periodic audits.
Definition
| N/A |
Related Documents
| N/A |
EHS Statement
There is no EHS impact.
Procedure
1. General
The APR will determine the need for revalidation of processes or methods, changes in product specifications, manufacturing and control procedures as well as evaluation of the need for regulatory notification supplements to regulatory submissions.
For the analysis, in process control results as well as the finished product laboratory results from all lots manufactured or tested during the review period should be considered unless the total number of lots is equal to or exceeds fifty. If this is the case the data for evaluation should be a representative sampling of the lots produced. Selection of lots should be based on a predetermined frequency (e.g. first four lots manufactured each month) in order to eliminate effect of seasonal changes on product characteristics and allow the inclusion of released as well as rejected lots.
If less than three batches of a product are manufactured in the review period, the APR will be delayed until at least 3 lots are available for the review or until the next review period where two years of data will be reviewed.
The first and last batch in the review period will be determined by the final disposition date of each batch. The QA department will determine the lots included and list sent to all departments.
The management will present recommendations for preventative and corrective actions related to any trends observed at quality team meeting for discussion and approval.
The QA staff will maintain an update calendar, which establishes the yearly schedule for all product belonging to the site.
All data provided must be inclusive of a source document reference and the issue/effective date in order to assure traceability of the incorporated information.
All partial batch rejection must be reported in the APR as well as total batch rejections.
A schedule for the complaint of APR data and completion of APR reports should be compiled and reports reviewed in a timely manner. Any overdue reports should be notified to the quality meeting.
2. Responsibilities
The following responsibilities apply to the preparation, coordination and review of the APR’s
The QA department is responsible for overall coordination and administration of the APR’s, ensuring that the reports are issued in a timely manner after collection of the data, tracking of any action items arising from the review and for review of the data supplied prior to finalizing each APR. The QA department is responsible for the compilation and collation of the APR document by ensuring that all departments supply the required data and time lines for the receipt of data are met.
The QA manger or the delegate will provide a summery report of Deviation Reports. In addition the QA department will provide any reworks/ reprocessed / returned drug products and salvaged materials for the review period, number of lots produced, rejected or uncompleted (including partial lot rejection) and the list of lot numbers reviewed in the APR.
The laboratory manager or delegate will provide the raw materials control information, all finished product release and stability test results, Deviation report summaries and retention sample review results. The laboratory manger will also provide information on all relevant method validation activities.
The technical service manager or delegate will provide a summery of the manufacturing /packaging validation activities and an evaluation of critical equipment changes during the review period. These evaluations must assess the impact of changes on the product. Technical service will also be responsible for summarizing change control information and investigations not captured in the discussion of Deviation reports.
The engineering manager or delegate will provide summery data on equipment evaluation carried out by engineering department. This data must be accompanied by an assessment of the impact on the product.
The operations manager or delegate will provide information on all recalls executed and product complaints received during the review period for the product under evaluation together with a summery of correspondence conducted with regulatory bodies.
The Operations manager or delegate will provide a list of lots assigned for manufacture during the review period, lot yielded data, in-process results and product reconciliation information
The regulatory manager will provide a summery of regulatory changes or requirements for the review period that affected the product.
3. APR report evaluation and final Report retention- Responsibilities
The QA staff will circulate the APR draft report to the appropriate department manager or designee for review and comments as follows:
– QA
– Regulatory
– Manufacturing
– Technical Service
– Laboratory
Other support department as applicable
Comments and/or recommendations must be addressed to the QA staff on or before the next scheduled quality meeting. The recommendations will be assessed in the meeting and included in the APR if necessary.
A summery of the APR report should be presented to the management team for review and approval. The summery should be attached to the final report for filing.
The QA department should track completion of the recommendations.
The APR final report will be filed in the QA office. The APR final report should be retained for a minimum of seven years.
4. Procedure Steps
Section | Data source | Applicable statistical analysis/ Quality tools | Report format |
General information (introduction) Review period Product name Packaging configuration Description Approved manufacturing, Packaging, release and stability testing sites Manufacturers of actives | Batch documentation Packaging records Master file documents APR calendar Regulatory submission Registration documents Certified product details | None | Tabulate and/or summarize |
Batch Size Product batch size Specification numbers for intermediate, bulk and finished products Packaging components Changes in components BPN numbers that were reviewed in the APR Total or partial lot rejection numbers | Master file documents Bill of materials | None | Tabulate and/or summarize |
Approved product Changes Change requests associated with the master file documents List of active ingredients and excipients with their specifications and test report, issue number, approved manufacturer or supplier, implementation date, and source of change. | Approved change control requests and/or in progress during the review period. Stability data from laboratory | None | Tabulate and/or summarize |
Validation Gather information regarding periodic maintenance of critical systems and equipment Identify lots manufactured after significant changes and assess the change in quality | Validation reports (Technical Service and Laboratory) Maintenance of equipment (Engineering) Assess the changes made to critical process parameters, equipment, facilities, and utilities | None | Tabulate and/or summarize |
Product recall and retuned goods evaluation | Review relevant Deviation Reports. If applicable Obtain a list of returned goods from QA department | None | Tabulate and/or summarize |
Deviations Deviation number, lot number, Date issued/closed, category, stage, deviation description Evaluate and denote the corresponding section of the APR that reports any trend in deviations. | Batch records Packaging records Obtain the summery of deviations that includes all investigations during the review period | Pareto Analysis Pie chart | Tabulate and/or summarize |
Analytical Results – results listed include but not limited to: Assay test %RSD %LOD Identify lots released, pending, cancelled, rejected, validation Intermediate and finished product test results Evaluate trends Comparison of results against limits | C of A Raw Material specification and test report Finished Product Specification and Test Report Controlled methods | – Average – Range – Standard deviation – Process capability analysis providing the results are normally distributed. – Graph results – Slope | Tabulate and/or summarize |
Results for in-process testing In-process controls recommended by manufacturing Yield and reconciliation results of all manufacturing steps as stated in batch documents. Attributes inspection results, if applicable Evaluate in-process and yield data using statistical tools. Denote any observed trends Summarize product defects from attribute inspection results | Batch Documentation | – Average – Range – Minimum – Maximum – Normality – Standard Deviation – Process capability | Tabulate and/or summarize |
Rework- re-inspection/repacking | Obtain a list of lots those have been reworked or repacked during the review period form the QA | None | Tabulate and/or summarize |
Stability Evaluate or highlight any trends, stability failures and deviations. Investigations and conclusions must be assessed and documented For a new product, where applicable, the APR must include an assessment of the stability data of commercial lots against those of the filing lots. The evaluation must continue until completion of stability studies. | Obtain a list of all commercial lots in the stability monitoring program, including the reason for stability from the laboratory. Stability scan card | – Average standard deviation – Graphs- for each test using specifications – Linear regression when six or more periods are reported for each study | Tabulate and/or summarize |
Visual inspection of retention samples Present the results of visual examination of a representative number of sample in primary packaging containers | Obtain a report of all retained samples examined during the review period from the laboratory. | None | Tabulate and/or summarize |
Product Quality Related complaints Review information for possible trends and document findings and action taken | Obtain a report of all complaint received during the review period form the QA department. | None | Tabulate and/or summarize |
Critical Equipment and facility evaluation | Obtain a summery of evaluation conducted for critical equipment during the review period form the Technical Service and engineering department. | None | Tabulate and/or summarize |
Regulatory compliance Review any commitment pending from the previous period Evaluate corrective actions for closure | Review available information regarding regulatory filing changes, inspection observations, Product certifications as applicable. | None | Tabulate and/or summarize |
Evaluation/recommendation and/or comments Evaluate all information obtained during the APR preparation Present if product quality characteristics shows a particular trends Comment on activities, accomplishments, enhancement conducted during the review period, if any Determine the need for changes, if any based on the report evaluation If changes are recommended as a result of this evaluation they should be minimally agreed by the site management team. | Previous APR Documents reviewed Management evaluation | N/A | Tabulate and/or summarize |
Summary of Changes
Version # | Revision History |
QMS-060 | New |