Longze Cui - Academia.edu (original) (raw)
Papers by Longze Cui
M M icrobial expression systems play an essential role in today's biopharmaceutical processes. Re... more M M icrobial expression systems play an essential role in today's biopharmaceutical processes. Recombinant E. coli and yeast systems are dominant tools in early discovery of effective medical targets. These systems are also routinely used to produce biological reagents for analytical methods in research and quality controls of products. In the biopharmaceutical industry, microbial systems have delivered major medicines such as blood proteins (factors VIII and IX), G-CSF, tPA, recombinant hepatitis B vaccine, interferons, interleukins, and human growth hormone (1). Microbial systems continue to improve to meet the challenges in expressing new and more complex biomolecules (2, 3). The advantages of microbial systems over mammalian systems are clearly recognized for their short development cycles and substantially lower manufacturing costs. Microbial process development is an integrated activity involving science, engineering, and regulatory requirements. Process development professionals must master microbial science and technology and thoroughly understand key quality issues and regulatory drivers. THE BIG PICTURE: KEY KNOWLEDGE AND DEVELOPMENT DRIVERS Biopharmaceutical development competes on the basis of effectiveness and efficiency. The winning criterion of process development is to deliver a predictably stable and reliable process over a short development time. The following areas contain key knowledge and drivers for success. The biology of microbial expression systems includes the microbiology of the host cell line, especially its physiology relating to cell growth dynamics, nutrient use, and metabolism. It is important to understand the plasmid vector system, its control and stability. Understanding process parameters for controlling protein expression kinetics in soluble (or secreted) and insoluble (inclusion body) phases is critical (4-6). Process Engineering and Manufacturing Ability: This area includes process design, control, and monitoring as well as process scaleup, equipment specifications, and considerations of manufacturingpractice issues. It is important to follow the advances of new process technologies that may significantly affect the direction of process development. Methodologies for Design, Development, and Project Management: Process development efficiency can be improved significantly by the use of smart experiment-optimization methods. Effective methods include statistical design of experiments (DOE) for screening and optimization of critical process parameters, control charts and standard deviation analysis for evaluating process
M M icrobial expression systems play an essential role in today's biopharmaceutical processes. Re... more M M icrobial expression systems play an essential role in today's biopharmaceutical processes. Recombinant E. coli and yeast systems are dominant tools in early discovery of effective medical targets. These systems are also routinely used to produce biological reagents for analytical methods in research and quality controls of products. In the biopharmaceutical industry, microbial systems have delivered major medicines such as blood proteins (factors VIII and IX), G-CSF, tPA, recombinant hepatitis B vaccine, interferons, interleukins, and human growth hormone (1). Microbial systems continue to improve to meet the challenges in expressing new and more complex biomolecules (2, 3). The advantages of microbial systems over mammalian systems are clearly recognized for their short development cycles and substantially lower manufacturing costs. Microbial process development is an integrated activity involving science, engineering, and regulatory requirements. Process development professionals must master microbial science and technology and thoroughly understand key quality issues and regulatory drivers. THE BIG PICTURE: KEY KNOWLEDGE AND DEVELOPMENT DRIVERS Biopharmaceutical development competes on the basis of effectiveness and efficiency. The winning criterion of process development is to deliver a predictably stable and reliable process over a short development time. The following areas contain key knowledge and drivers for success. The biology of microbial expression systems includes the microbiology of the host cell line, especially its physiology relating to cell growth dynamics, nutrient use, and metabolism. It is important to understand the plasmid vector system, its control and stability. Understanding process parameters for controlling protein expression kinetics in soluble (or secreted) and insoluble (inclusion body) phases is critical (4-6). Process Engineering and Manufacturing Ability: This area includes process design, control, and monitoring as well as process scaleup, equipment specifications, and considerations of manufacturingpractice issues. It is important to follow the advances of new process technologies that may significantly affect the direction of process development. Methodologies for Design, Development, and Project Management: Process development efficiency can be improved significantly by the use of smart experiment-optimization methods. Effective methods include statistical design of experiments (DOE) for screening and optimization of critical process parameters, control charts and standard deviation analysis for evaluating process