Quality Management Systems (QMS), be it ISO or PIC/S, mandate that system reviews must occur. Product Quality Reviews (PQR) can provide the ideal platform not solely to fulfill a compliance requirement but to give real insight into the performance of critical QMS aspects.
The premise of any QMS procss and PQQR leverage this where:
- Plans are developed – explains what to review
- Work or processing occurs – actually performs a process
- Process are checked or reviewed – reviews the process performance for improvement opportunities
- Action opportunities to improve the QMS, the process and the input data.
Regulatory InfluencesThe intent of the PQR methodology is to verify the consistency of existing processes and whether existing specifications are appropriate and adequate. This methodology is expected to highlight any trends fundamental in the comprehension of QMS data and performance, to identify opportunities for real, sustainable improvement.
The influence of regulators and organisations such as ICH is clear in the PQR process.
For example, according to ICH Q10 the Pharmaceutical Quality System objectives include;
- Achieve product realisation
- Establish and maintain a state of control
- Facilitate continual improvement
In the words of ICH Q10, “Management review should provide assurance that process performance and product quality are managed over the lifecycle”.
PQRs are designed to verify the consistency of existing processes, in other words, the effectiveness of control strategies that are in place.
Control strategies are the collective process controls and all that you do to produce an acceptable quality product. Not everyone will be familiar with the term Control strategy, but you still have one! Consider everything you do on a day-to-day basis to achieve and verify product quality.
The High-Level Process Flow
Clause 1.4 of the PIC/S cGMP refers to “Regular periodic or rolling quality reviews of all licensed medicinal products…” This will pose one of the single biggest challenges to those in the regulated industries. In general, PQRs are conducted and documented annually, however this frequency needs to be justified. Are you working with a novel or recently redesigned product/process in the absence of established QMS data? This novel product/process may require more frequent, detailed reviews.
Are you working with a legacy product/process that is well controlled and established? Then consider your QMS data, are you able to identify trends and are you still in a reactive mindset unaware of the next issue lurking? PQRs should be used to identify gaps in data and trends to continuously improve the product and process performance.
Alignment with USFDA
CFR 211.110 (b): “[in process specifications] shall be derived from previous acceptable process average and process variability estimates where possible.”
CFR 211.180 (e): “[in process specifications] require that information and data about product quality review and manufacturing evidence be periodically evaluated to determine the need for changes in specifications or manufacturing or control procedures.”
Yes, there is so much work to be done. Here’s where a robust QRM effort can be used to drive compliance initiatives. Consider ‘grouping’ your products. Grouping may occur, based on a science-based justification, according to;
- Formulation type
- Product type
- Equipment ‘train’
There are 12 components for review detailed in the PIC/S cGMP (Could this be a link to the GMP guide or is that frowned upon?)
- Starting and packaging materials, especially those sourced from new suppliers.
- Critical in-process controls finished product results.
- All failed batches and the subsequent investigations.
- Significant deviations and non-conformances, the subsequent investigations and the effectiveness of corrective and preventative actions.
- All process and analytical method changes.
- Marketing Authorisation variations.
- Stability monitoring programme results and trends.
- Quality relevant returns, complaints, recalls and the subsequent investigations.
- Effectiveness review of product process or equipment corrective actions.
- For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.
- Qualification status of equipment and utilities.
- Contract Manufacture and Analysis contractual arrangement review.
Keep in mind, that the PQR process is at the mercy of the input data quality, but we’ll leave that for another article!
It’s important to comprehend the Pharmaceutical Inspection Cooperation Scheme; it provides greater insight regarding the intent of PQRs and how the PQR process lends from a series of other GMP initiatives.