Morphological Engineering of Filamentous Fungi: Research Progress and Perspectives.

Filamentous fungi are important cell factories for the production of high-value enzymes and chemicals for the food, chemical, and pharmaceutical industries. Under submerged fermentation, filamentous fungi exhibit diverse fungal morphologies that are influenced by environmental factors, which in turn affect the rheological properties and mass transfer of the fermentation system, and ultimately the synthesis of products. In this review, we first summarize the mechanisms of mycelial morphogenesis and then provide an overview of current developments in methods and strategies for morphological regulation, including physicochemical and metabolic engineering approaches. We also anticipate that rapid developments in synthetic biology and genetic manipulation tools will accelerate morphological engineering in the future.

Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs.

To identify key challenges and propose technical considerations in designing electronic case report form (eCRF) for post-marketing studies, the author undertakes a comprehensive literature review of peer reviewed and grey literature to assess the key aspects, processes, standards, recommendations, and best practices in designing eCRFs based on industry experience in designing and supporting electronic data capture (EDC) studies. Literature search using strings on MEDLINE and PUBMED returned few papers directly related to CRF design. Health informatics and general practice journals were searched and results reviewed. Many conference, government commission, health professional and special interests group websites provide relevant information from practical experience - summarization of this information is presented. Further, we presented a list of concrete technical considerations in dealing with EDC technology/system limitations based on literature assessment and industry implementation experience. It is recognized that cross-functional teams be involved in eCRF design process and decision making. To summarize the keys in designing eCRFs to address post-market study safety and pharmacovigilance needs, the first is to identify required data elements from the study protocol supporting data analyses and reporting requirements. Secondly, accepted best practices, CDASH & CDISC guidelines, and company internal or therapeutic unit standard should be considered and applied. Coding (MedDRA & WHODD) mapping should be managed and implemented as well when possible. Finally, we need to be on top of the EDC technologies, challenge the technologies, drive EDC improvement via working with vendors, and utilize the technologies to drive clinical effectiveness.

Information technology in pharmacovigilance: Benefits, challenges, and future directions from industry perspectives.

Risk assessment during clinical product development needs to be conducted in a thorough and rigorous manner. However, it is impossible to identify all safety concerns during controlled clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with comorbid conditions and those being treated with concomitant medications. Therefore, postmarketing safety data collection and clinical risk assessment based on observational data are critical for evaluating and characterizing a product's risk profile and for making informed decisions on risk minimization. Information science promises to deliver effective e-clinical or e-health solutions to realize several core benefits: time savings, high quality, cost reductions, and increased efficiencies with safer and more efficacious medicines. The development and use of standard-based pharmacovigilance system with integration connection to electronic medical records, electronic health records, and clinical data management system holds promise as a tool for enabling early drug safety detections, data mining, results interpretation, assisting in safety decision making, and clinical collaborations among clinical partners or different functional groups. The availability of a publicly accessible global safety database updated on a frequent basis would further enhance detection and communication about safety issues. Due to recent high-profile drug safety problems, the pharmaceutical industry is faced with greater regulatory enforcement and increased accountability demands for the protection and welfare of patients. This changing climate requires biopharmaceutical companies to take a more proactive approach in dealing with drug safety and pharmacovigilance.