Department | Quality Management | Document no | QMS-170 | ||
Title: Product Quality Reviews for Contract-Manufactured Products | |||||
Prepared by: |
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| Supersedes: |
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Checked by: |
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Approved by: |
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1.0 DOCUMENT OWNER
Technical/Quality Manager
2.0 PURPOSE
The purpose of this procedure is to describe a process for the preparation, review and approval of Product Quality Reviews (PQR) for products that are the responsibility of Contract Operations Management of Quality Assurance Team.
3.0 SCOPE
This procedure applies to products manufactured or packaged by a contract manufacturer managed by Contract Operations – Quality Assurance.
4.0 RESPONSIBILITY
4.1 It is the responsibility of the contract manufacturer to either:
4.1.1 Provide PQR report/s as per agreed PQR schedule, Or
4.1.2 Provide data as per Quality Agreement to enable PQR to be prepared.
4.2 It is the responsibility of the QA Officer or delegate to ensure that:
4.2.1 The PQR schedule is prepared based on approved Quality Agreements.
4.2.2 PQRs for contract manufactured or packed products are completed in compliance with the established PQR schedule.
4.2.3 The contract manufacturer generated PQR, including conclusions and recommendations, are reviewed, where available.
4.2.4 An Sponsor site PQR report is generated, where applicable.
4.2.5 A PQR executive summary is compiled for both Sponsor site and contract manufacturer PQR reports and submitted to monthly Site Quality Team meetings for review.
4.2.6 An action plan to address recommendations is established and progress is tracked.
4.2.7 The completed PQR and executive summary is forwarded to Key Site Principals for approval.
4.3 It is the responsibility of the Site Quality Team and/or Key Site Principals to:
4.3.3 Review the PQR executive summary and recommendations
4.3.4 Make or endorse recommendations, if necessary, for preventative or corrective actions that would lead to product quality improvements.
4.3.5 Agree on actions, responsibilities and target completion dates for each recommended action for tracking.
4.4 There should be a maximum of three (3) years between quality reviews of contract manufactured products, unless fewer than three batches have been manufactured in the review period.
4.5 Where the number of batches for the review period is >50, a representative number of lots may be used. Selection of lots may be based on a predetermined frequency (e.g. every 3rd lot manufactured) in order to eliminate the effect of seasonal changes on product characteristics and allow inclusion of released as well as rejected/quarantined lots.
4.6 For those products with < 50 batches, all batches will be considered for analysis.
4.7 PQR reports will not be compiled on products that have been discontinued.
4.8 A PQR report and executive summary must be compiled within 3 months from the period indicated in the PQR schedule.
4.9 The PQR and executive summary must be approved within 3 months of circulation.
5.0 PROCEDURE
For Sponsor site-generated PQR reports, prepare a suitable PQR report that details each of the following areas. PQR reports should include the following data:
5.1 Batches Manufactured
5.1.1 Record the total number of batches manufactured during the review period including the batch disposition (released, reworked, rejected, awaiting disposition, etc.).
5.1.2 All batches with a manufacturing date during the review period are to be included in the review. The review period ends the last day of the month prior to when the product review is initiated and begins the first day of the month, a year previous.
5.1.3 Batches that have been reprocessed or reworked including repackaged product must be identified and reported accordingly.
5.1.4 Document any deviation and/or contractor deviations associated with batches and provide a brief description of issue.
5.2 Product Change Requests (PCRs) and/or Contractor’s Change Control
5.2.1 Record and review any quality related changes initiated by the contractor or Sponsor site during the review period.
5.2.2 Record any regulatory submissions for countries marketing the product during the review period.
5.3 Validation
5.3.1 Record and review manufacturing and packaging processes, cleaning, computerized systems, raw material evaluations and analytical method validation studies impacting the Sponsor site’s contract manufactured products during the review period.
5.3.2 Identify which batches are affected by any validation activities.
5.4 Customer Complaints
5.4.1 Review and summarize all quality-related complaints received in the countries of sale of the product during the review period. Include corrective actions taken to rectify the issue.
5.4.2 Identify any significant trends in regard to the type of complaint and the batch number
5.5 Market Actions and Recalls
5.5.1 Record and review any recalls or market actions for the product initiated during the review period.
5.5.2 Summarize the reason for recall, extent of recall (batch numbers and area recovered from), percentage of units retrieved and the current status of the product recall.
5.6 Deviations
5.6.1 Summarize any manufacturing, packaging or analytical (including stability) deviation reports, which were raised by the contractor.
5.6.2 Summarize any Sponsor site deviations raised in relation to any contractor activities.
5.6.3 Identify any trends or repeating issues, which may require corrective actions to eliminate reoccurrence.
5.7 Out-of-specification (OOS)
5.7.1 Summarize any significant OOS results obtained during QC testing for both release and stability testing, if available.
5.7.2 Identify any trends or repeating issues, which may require corrective actions to eliminate reoccurrence.
5.8 QC Data and Statistical Analysis
5.8.1 Record the chemical analytical data for the finished product in a tabular or graphical format.
5.8.2 Evaluate the data against the registered specifications. Identify and investigate any adverse trends in the data during the review period.
5.8.3 Statistical analysis is to be conducted on the finished product data for the API assays and any other critical parameters using Minitab (a statistical software program).
5.8.4 The normality plot, Individual Value-Moving Range (I-MR) charts and process capability analysis should be applied where possible. Process Capability analysis can only be applied when both the data is normally distributed and in a state of control.
5.8.5 Review microbial data against the release and/or registered specifications for compliance.
5.8.6 Review the raw material (API) QC data for those materials supplied by the GMP site to the relevant contractor for the manufacture of products.
5.9 Stability Data
5.9.1 Summarize all ongoing stability studies initiated and conducted during the review period by either the contract manufacturer or Sponsor site’s QC laboratories. This responsibility is outlined in the relevant Quality Agreement.
5.9.2 Summarize all evaluation stability studies initiated and conducted during the review period and identify the reason for the evaluation study.
5.9.3 Review the available data and identify whether the registered shelf life and storage conditions are suitably supported.
5.10 File Samples
5.10.1 Visually examine the file samples of batches manufactured during the review period for overall packaging, coding and seal integrity.
5.10.2 Record any evidence of deterioration to the packaged product (eg, split tubes, leaking product, etc) or product defects and the date of inspection.
5.10.3 Retain all file samples in the dedicated file retention room.
5.11 Returned Goods
5.11.1 Summarize all returned goods for the product under review during the review period, including the reason for return and returned quantity.
5.11.2 Identify any trends in credit returns relating to quality issues,
5.12 Product Quality Executive Summary
The PQR executive summary should include, but may not be limited to, the following:
5.12.1 Summaries of findings described in the supporting data;
5.12.2 Current status of any corrective or preventative actions that were identified during the previous PQR;
5.12.3 Recommendations for preventative or corrective actions that may lead to product quality improvements;
5.12.4 An action plan which includes responsibilities and a target completion date for each recommended action; and
5.12.5 Conclusion summarizing the product’s current state of control against validated and registered process.
5.12.6 All agreed recommendations with responsibility and timeline are recorded and maintained by the QA Officer or delegate.
5.12.7 Completed approved PQRs will be filed by QA and maintained as per SOP – “Documentation Retention Policy”.