PRODUCT QUALITY REVIEW (PQR)
The product quality review is an effective quality
improvement tool to improve the consistency of the process and the overall
quality of the product. The Product quality review will capture a broader view
of product data, capturing trends and will help determine the need for
re-validation and changes, if any.
All the major regulatory authorities define the requirement
of product quality review for example:
•
European Union (Eudralex):
–
The additional text “Product Quality Review” for Chapter 1 to the EU GMP
Guide has been adopted by the Ad hoc GMP inspectors Working group at their
first meeting in July 2003. The proposal of Product Quality Review arises from
the experience of Member States’ inspectorates where quality problems with
products on the market leading to recall could have been anticipated if the
manufacturer/marketing authorization holder had operated a system for formally
reviewing process consistency and trends.
•
US FDA:
–
The code of federal regulations (CFR) of Food and Drug Administration in
their 21 CFR – Parts 210 & 211 dictated the requirements of reviewing the
products annually. It is clearly stated under Subpart J - Records and Reports
211.180(e) that written records required by the part shall be maintained so
that data can be used for evaluating, at least annually, the quality standards
of each drug product to determine the need for changes in drug product specifications
or manufacturing or control procedures.
•
ICH:
–
ICH Q7 GMP Guide for API requires
manufactures to conduct annual quality review of the active pharmaceutical
ingredients in order to know the consistency on the quality of products
manufactured through out the year.
- Consistency of the existing process(es)
- Trends in product data
- To verify compliance of product
- Deficiencies not detected by routine testing, performance metrics
- Identify opportunities for product and process improvement.
- Carried out for each product manufactured in the previous years
- Use a risk base approach and
- Review from previous year
PQR schedule
is documented for each product/group of product within a PQR. If less number of
batches were manufactured with 12 month, a PQR could be conducted every two
years. In such cases associated risk to be evaluated.
PQR can be prioritized
considering the recurring deviation on critical parameter, recalls, complaints,
return and process changes.
A PQR report
should be prepared to ensure a standardized documentation approach.
- Product name;
- Batch size;
- Review period;
- Reference of source documents;
- Comparison with previous PQR;
- Identification of issues or trends;
- Name and signatures of the person responsible for preparing, review and approving the report.
Product Quality Review should normally include:
- Review of starting material and packing material used for the product. This include name of suppliers/manufacture of the materials, significant deviations, inspection rejection rate, change in production process or specification by suppliers and result of analytical tests.
- A review of critical in-process controls, and finished product results. Trending may take consideration physical variations, chemical variation, rejection units. Yield reconciliation from stages of manufacturing process.
- A review of all batches that failed to meet the specification and their investigation. List of deviation and non-conformance associated with the product. Current status of investigation with summary of reason of failure, completed investigation, CAPA and its effectiveness action.
- A review of all significant deviations or non-conformance, the related investigations and the effectiveness of resultant CAPAs taken.
- Review of all changes made to the process or analytical methods. The change assessment should be considered both closed and approved to commence during the review period. Review the effectiveness of the change on the batch under review.
- A review of market authorization/ number of dossier variation submitted, granted or refused. Variation submitted, whether or not they have been granted or refused. If refused, the impact should be assessed and documented.
- A review of stability programme and its trends. Include product information such as manufacturing date, Expiry date, shelf life etc. . Review of any out of specification results. Review of long term and on-going stability of the bulk and marketed product.
- A review of all quality related returns, complaints and recall along with investigation performed at the time. This include batch numbers, reason for return/complaint/recall, action taken and impacted batches and current status.
- A review of past PQR responses to confirm the review and report on previous PQR CAPAs and change implementation status.
- The equipment qualification status of relevant equipment and utilities eg HVAC, water, process gases etc.
- Review of contractual arrangement to ensure they are up to date. Review contract for services associated with the product in review and confirm that the services provided are aligned with the marketing authorization.
Appropriate
statistical analysis technique should be used to review the data collected as
part of the PQR. Process capability study to be used to established that the
process is capable for consistently manufacturing of product with defined limit
and standards. It is recommended that the Cp/Cpk values are targeted at 1.33 or
above. Analysis must be interpreted and documented. Proposed action and
conclusion, including justification for not implementing action when the PQR
has revealed an adverse trend on product quality must also be documented in the
PQR report.
Reference:
1.
Guidance for industry: Product Quality review version
1.0
2.
WHO good manufacturing practices for pharmaceutical
products: main principles TRS 986 annex 2.
Knowledgeable article and very helpful to understand PQR reauirequire as current trend.
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