Product quality review

Two important aspects are internal audits and product quality review. Internal audits are implemented to regularly monitor the compliance activities in drug manufacture and to ensure rectification to these activities if deviations occur. Trending and statistical analysis of data provide early warning of impending problems. Product quality review checks the relevance and adequacy of the manufacturing activities. It provides input to update and improve the quality system. 

It has been found in the Netherlands by proficiency testing that the average content of most pharmacy preparations lie between 95 % and 105 % of the stated content. So when accepting a content limit of 90-110 %, the product will be released without further consideration if an assay result is between 95 % and 105 %. Trends in results (up or down) should be investigated as part of product quality reviews. 

By performing trend analysis on the historic results, intended or unintended deviations in the preparation process can be traced. Also occasional errors can be easily detected. The results of such trend analysis are therefore also part of the product file and form a Product Quality Review. 

A separate part of the product file includes the aftercare around the preparation regarding an evaluation of all failures or discrepancies. Information on complaints, deviations and recalls is collected in this section, including the details of how these were handled. Based on all the information in this section, it is possible to perform evaluations such as Product Quality Reviews (see also Sect. 35.6.11) to look at the robustness of the preparation and the need for change. Also this information may be useful to determine a frequency for how often the product has to be reviewed. 

Automated systems Process validation of unit-operations Cleaning methods Analytical methods Furthermore it must be assured that relevant documentation is up to date and available. If data from Product Quality Review (PQR, see Sect. 35.6.11) and stability testing are available they should be evaluated in order to identify any critical aspect of the processes. If not available related quality indicators, such as test results, deviations and complaints should be evaluated. 

Presentation and discussion of key performance indicators in relation to product quality, such as recalls, complaints and adverse events, non-conformities, out of specifications (OOSs), any conclusimis from product quality reviews, rejections... 

The quality of the design has to be monitored, with help of a regular review of results of analysis, complaints, recalls etcetera. In order to frame that activity into the PQS, the term Product quality review is used. GMP Chap. 1 emphasises the importance of product evaluation an annual evaluation of product quality for every product, and a risk analysis as well. A Product Quality Review has 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 . 

Well-known elements of a Product quality review are (see also GMP Chap. 1) ... 

Product quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, sterile products, etc. where scientifically justified. This is an appropriate approach for a quality review of non-standardised pharmacy preparations, see also Sect. 34.14.3. 

The handling of non-conformities and the actual content are to be included in product quality reviews and management reviews. 

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