PAT & QbD SUPPLEMENT


quantitation by near-infrared (NIR). NIR is designed to predict accurately within a specific set of samples and conditions. Deviation from these samples can cause greater predictive variances. This can be compensated for by either


“Qualitative methods can provide information more quickly and this is of particular value if the PAT


method is developed alongside product development”


including all critical conditions and material variances within the control systems calibration design or combining the predictable models with the critical process parameters in real time to produce an enhanced prediction. The agility of NIR quantification methods however is debatable, and although it provides information that is clearly transparent, it does require a significant amount of time spent in development. Qualitative methods can provide


information more quickly and this is of particular value if the PAT method is developed alongside product development. Not only will it benefit from the same lifecycle documentation, but also


many of the exploratory studies into formulation can use PAT and QbD principles to generate understanding of the product which can then be used to inform development. As QbD can be applied in the initial


developmental stages, it will ultimately involve several changes in scale. This can also reveal discrepancies in the formulation processing between scales and may require additional supporting studies. The understanding gained from the development can then be applied to ease the transition. This information can then be fed back to the PAT method and may ease transition from a qualitative method to a more established quantitative method as the process matures.


Conclusion The regulatory framework that has been put in place integrates the different principles of risk analysis, QbD and PAT within pharmaceutical development. The integration of these principles results in significant opportunity for cost savings and product enhancement, whilst offering the potential for more robust and process hardened manufacture. This will facilitate the movement away from the current


reactive model to a more pro-active approach where flexible processing assures product quality. This can only be beneficial to regulators manufacturers and ultimately the patient.


References


1. ICH Q8 – Pharmaceutical Development, International Conference on Harmonisation, August 2009


2. ICH Q9 – Quality Risk Management, International Conference on Harmonisation, November 2005


3. ICH Q10 – Pharmaceutical Quality System, International Conference on Harmonisation, June 2008


4. PAT – A framework for innovative pharmaceutical development, manufacturing and Quality assurance, September 2004


5. Manufacturing Chemist, March 2011


6. Arden House Conference Presentation, Roy Scherzer 2001, London


Mark Morton began his career in Quality Control where he successfully implemented raw material identification and final product release testing by near-infrared spectroscopy. In 2008, he received his Doctorate from the London School of Pharmacy and is a six-sigma


black belt. He currently divides his time between consultancy and contract work.


SentroPAT NIR as a powerful PAT tool for High Shear Wet Granulation


Several technologies have been tested to apply PAT to High Shear Wet Granulation as one of the most critical processes in solid dose production. One of the results of this intensive work done in scientific and industrial research is that NIR is the only tool that provides chemical and physical information. Whilst FBRM gives physical information and moisture measurement gives chemical information, NIR combines both and is a multi parameter PAT tool for this unit operation. The success of the implementation of an


NIR system to this process depends again on the


technology. Due to the moving product and poor sample presentation in some phases of the process, a technology is required that is not impacted by these effects. Diode array spectrometers turned out to be the best choice. They are much faster than FT-NIR or scanning instruments. The Sentronic solution for this challenging PAT application is the SentroPAT NIR system combined with the unique SentroProbe DR LS. The SentroPAT NIR is based on a diode array and achieves a typical integration time of only 10 ms. Applying an averaging of single spectra, an overall


measurement interval of 1 sec or less is given. But even further, a diode array NIR detects all wavelengths of the spectrum simultaneously. This is totally different to all other NIR technologies including FT-NIR. When sample presentation is not constant during the process, every single spectrum looks smooth, only the baseline might be at different heights. Fast variations in the sample or sample presentation would make the spectrum unusable or very noisy in these cases.


email: info@sentronic.eu Tel: +49 351 871 8653


www.sentronic.eu www.europeanpharmaceuticalreview.com


European Pharmaceutical Review 15 Volume 16 | Issue 3 | 2011


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