No abstract

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader.

• This is a journal article. It was published in the Chemical Engi- The purpose of the paper is twofold: it describes the proof of concept of the newly introduced bulk video imaging (BVI) method and it presents the comparison with existing process analytical technologies (PAT) such as focused beam reflectance measurement (FBRM) and ultra violet/visible (UV/Vis) spectroscopy. While the latter two sample the system in small volumes closely to the probe, the BVI approach monitors the entire or large parts of the crystallizer volume. The BVI method is proposed as a complementary noninvasive PAT tool and it is shown that it is able to detect the boundaries of the metastable zone with comparable or better performance than the FBRM and UV/VIS probes.

External bulk video imaging (eBVI) of crystallization processes has proven to be a promising technique for metastable zone determination. In this contribution the endoscopy-based in situ bulk video imaging (iBVI) method is introduced. The video data are processed using the mean gray intensity method and by a digital image processing technique which aims to detect the first crystals during nucleation. The experiments have been carried out in a small-scale calorimeter CRCv4, during which the compensation heater and infrared spectroscopy signals were monitored. It is concluded that monitoring the onset of the apparent nucleation, formation of particles with detectable size, using the mean gray intensity (MGI) trend delivers similar performance to the calorimetric and IR spectroscopy signal, whereas the crystal recognition method is the fastest, allowing detection of nucleation earlier. The endoscopy-based nucleation monitoring technique is proposed as a complementary tool to existing process analytical technologies (PAT) since it provides an in situ, low-cost, robust, probe-based method for metastable zone identification which can be easily integrated and automated with existing laboratory hardware and software.