Parametric Release and Real-Time Release Testing - Pharmaceutical Technology

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Parametric Release and Real-Time Release Testing
Medicinal products must comply with approved specifications before they are released into the market. Compliance with release specifications can be demonstrated by testing the final product, but, in certain circumstances, alternative strategies are available. Parametric release and real-time testing use manufacturing data to ensure that products are made according to defined standards.


Pharmaceutical Technology Europe
Volume 24, Issue 3

Q. Will real-time release testing replace the final release procedure?

The main benefit of RTR testing when combined with Quality by Design and PAT tools is increased quality assurance for patients. In addition, such a strategy can lower manufacturing costs through improved yields, less waste, faster cycle times, and fewer deviations and rejects.

Process understanding and the definition of a robust control strategy are key aspects of RTR. The interaction of material parameters and attributes, as well as the dynamics of processes, must be taken into account, and are one important part of submission dossiers for marketing authorisations. As such, when implementing RTR systems it is essential to use PAT to efficiently monitor and record all quality-relevant parameters. In this area, there have been a number of improvements, including advances in NIR- and Raman microscopy, fluorescence microscopy, image analysis and laser-based methods. Using chemometics and multivariate analysis, it is now also possible to monitor production processes in real-time. However, a move towards RTR is not only about using advanced analytical and physical measurement techniques, but also involves performing statistical calculations on the resulting data masses. Importantly, regulatory authorities worldwide have to accept the move from final product testing to RTR applications. RTR has to be accepted by all regulatory authorities because the current varied acceptance can be a major issue. The equivalence between RTR-testing and pharmacopoeial testing must also be explained.

If you do wish to implement new tests and procedures, then you will need to adapt the whole QA system. This is mandatory for compliance. The new quality system must also be aligned with ICH Q10.

These steps constitute the transition from rigid to risk-based cGMP, and a mindset change from reactive to proactive quality thinking, which could be quite a challenge. In particular, there will be a huge impact on qualified persons or other persons responsible for product release. Specifications will need to be elaborated carefully, and the definition of deviations that require investigation and the process to declare analytical results as outliers or invalid data must be described in SOPs.

RTR will be implemented over time as industry understanding increases and regulatory expectations are clarified. There is a long road ahead, but as the saying goes: a journey of a thousand miles begins with a single step.

Heribert Häusler Head of quality systems excellence at Boehringer Ingelheim GmbH (Ingelheim).

References

1. EMA, Note for Guidance on Parametric Release (March 2001).

2. EMA, Guideline on Real Time Release Testing (February 2010).

3. FDA, CFR — Code of Federal Regulations Title 21 (April 2010).


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