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Copepods are vectors of pathogens of other aquatic organisms, including commercially harvested species and those used for aquaculture. Extensive supplementary materials are provided, referencing copepod-associated eukaryotes, bacteria, and viruses. Phylogenetic analyses of dinoflagellate and microsporidian parasites of copepods show a wide phylogenetic distribution of parasitic lineages, with some copepod-infecting specialists and evolutionary radiations. The review provides an overview of recent high-throughput sequencing (microbiome, symbiome) studies of copepods and their physiological implications for marine ecosystems. Synthesizing the relationship between host, environment, and symbiome/pathobiome is important for understanding copepod health and population dynamics, and also the contribution of the copepod holobiont to biogeochemical cycling.There is a large diversity of eukaryotic symbionts of copepods, dominated by epizootic protists such as ciliates, and metazoan parasites. Eukaryotic endoparasites, copepod-associated bacteria, and viruses are less well known, partly due to technical limitations. However, new molecular techniques, combined with a range of other approaches, provide a complementary toolkit for understanding the complete symbiome of copepods and how the symbiome relates to their ecological roles, relationships with other biota, and responses to environmental change. In this review we provide the most complete overview of the copepod symbiome to date, including microeukaryotes, metazoan parasites, bacteria, and viruses, and provide extensive literature databases to inform future studies.

Size and shape distributions are among critical quality attributes of particulate products and their inline measurement is crucial for monitoring and control of particle manufacturing processes. This requires advanced tools that can estimate particle size and shape distributions from multi-sensor data captured in situ across various processing steps. In this work, we study changes in size and shape distributions, as well as number of particles during high shear wet milling, which is increasingly being employed for size reduction in crystalline slurries in pharmaceutical processing. Saturated suspensions of benzoic acid, paracetamol and metformin hydrochloride were used in this study. We employ our recently developed tools for estimating particle aspect ratio and particle size distributions from chord length distribution (CLD) measurements and imaging. We also compare estimated particle size distributions from CLD and imaging with corresponding estimates from offline instruments. The results show that these tools are capable of quantitatively capturing changes in particle sizes and shape during wet milling inline. This is the first time that such a capability has been reported in the literature. The ability to quantitatively monitor particle size and shape distributions in real time will enable development of more realistic and accurate population balance models of wet milling and crystallisation, and aid more efficient control of crystallisation processes.

In recent years, the pharmaceutical industry is seeing a movement towards the implementation of more efficient continuous manufacturing. This shift requires the development of in-line process analytical technologies to monitor and control the process at any given time. However, extracting reliable information from these sensors is a challenge. Among the available technologies, in-line image analysis is quickly gaining importance. This work presents an image analysis framework developed to address one of the main challenges of in-line image analysis: the presence of out-of-focus particles. Through two relevant examples such as the characterisation of a system of microparticles of mixed shapes and the monitoring of a common operation in the pharmaceutical industry such as the wet milling process, the benefits of incorporating this technique are assessed. The realtime analysis of imaging data in combination with other simultaneously-acquired quantitative data streams enables the user to make informed decisions and implement enhanced control strategies.

Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for pharmaceutical and chemical industry. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within

Introduction and objectives: In moving from batch to continuous manufacturing of pharmaceutical products, knowledge of all experimental variables is required to help control and achieve a stable system that yields a consistent product with the desired attributes. Spectroscopic tools are often used to provide point measurements at key points in the process. Here we demonstrate the applicability of Hyperspectral Imaging (HSI) to continuous nuclaetion processes. The objective of the work described here was to show how HSI can be used to monitor mixing processes by providing spatially discriminated near-infrared spectra, yielding vital process information that has only previously been estimated using simulation techniques such as computational fluid dynamics (CFD). Methods: Water (antisolvent) and an IPA/water mixture (solvent) containing dissolved paracetamol seed crystals were mixed in a tube by introducing the antisolvent jet at different flow rates, and the resulting mixing in the tube was imaged with an InnoSpec RedEye camera in the spectral range 950 to 1700 nm. Microscope images of the resultant crystals from each different flow rate were taken to confirm that differences in the final crystal product were observed. Machine learning techniques in the form of Support Vector Machine (SVM) analysis were used to analyse and automatically separate the spectral data of the solvent/antisolvent mix into the different components. Results: The antisolvent jet, which resulted in nucleation near the point of injection, could clearly be identified and therefore monitored after application of the SVM. Differences between different flow rates and concentrations were observed from the hyperspectral images obtained, and these differences carried through to the shape and size of the final crystals obtained. Conclusions: We have demonstrated the applicability of HSI and advanced data processing techniques to the monitoring of mixing dynamics, in particular those used in continuous pharmaceutical processing such as solvent/antisolvent crystallisation.