One of the important aspects of an effective Pharmaceutical Quality System is the Annual Product Review (APR) or Product Quality Review (PQR). As documented in Volume IV, Chapter 1 of the EU GMP Guide, these reviews are required for all authorised medicinal products, including export only products and they 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.’

Why are they done?

There are several reasons for preparing PQRs.

Apart from being a legal requirement to perform these reviews, they allow pharmaceutical companies to gain an in-depth understanding of the product, manufacturing processes, trends and risks.

They are useful to review whether re-validation is required for any systems and if new Corrective and Preventative Actions (CAPAs) need to be set up.

The benefits also include a basis for the adjustment of process, raw material and excipient specifications where necessary, better process controls and a reduction in Quality Defects.

PQRs result in enhanced product and process knowledge and they provide a more structured system for proactive improvement.

How are they done?

Responsibilities should be clearly defined for the preparation of PQRs. Typically, information is collected and analysed by each department/ Subject Matter Expert within the responsible company and this information is then compiled into a report. The reports are then reviewed and approved by the Quality Department. Where the product manufacture involves a complex supply chain with Contract Manufacturing Organisations (CMOs) and Contract Laboratory Organisations (CLOs), input from the various parties is needed. Once fully reviewed, recommendations and actions are identified for improvements or where risks are highlighted. Qualified Persons who are responsible for disposition of the product reviewed should be involved in the review of the PQR.

When are they done?

PQRs are usually prepared annually covering the retrospective review of a calendar year and ideally, they should be available no later than 3 months after the review period.

What topics should they cover?

The PQR should include a review of the following topics for the duration of the review period along with statistical analysis where applicable:

  • The batches manufactured including any major issues identified
  • Active Product Ingredients, raw materials and packaging materials, especially those from new sources and in particular the review of supply chain traceability of active substances.
  • Manufacturing & Packaging processes
  • In Process Controls (IPCs) and Critical Process Parameters (CPPs)
  • Finished product results
  • Out of Specification (OOS) and Out of Trend (OOT) results
  • Rejected materials/ batches
  • Deviations/ Non-conformances, their related investigations and the effectiveness of resultant corrective and preventive actions (CAPAs) taken
  • Change controls
  • Product returns, recalls and customer complaints and the investigations performed
  • Regulatory actions including Marketing Authorisation variations submitted, granted or refused and any post marketing commitments
  • Validation studies completed/ required and a review of Continuous Process Verification (CPV)
  • Results of the stability monitoring programme and any adverse trends.
  • Supplier qualification status (audits and Quality Technical Agreements)
  • Risk evaluation
  • For products that require importation testing from a third country, comparison of results obtained from importation testing and the third country laboratory in addition to the effectiveness of the sampling procedure

What challenges do they present?

One of the challenges associated with producing PQRs is keeping on top of the batch data. It is important to have clear roles defined within a written procedure to avoid any confusion and to monitor progress at regular intervals. This will make sure it isn’t a last minute effort and consistent data collection and review takes place. It can also be challenging to co-ordinate the input from several companies when the Supply Chain is more complicated but once there is proper communication and planning, any issues or delays should be avoidable.

Conclusion

In the Pharma world, data review, knowledge management and continuous improvement are key aspects of product Quality Assurance and patient safety. A detailed and thorough PQR facilitates process monitoring and can help to identify potential problems or process drift before they before they become an issue.

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