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Defining Process Design Space for Biotech Products: Case Study of Pichia pastoris Fermentation
Author(s) -
Harms Jean,
Wang Xiangyang,
Kim Tina,
Yang Xiaoming,
Rathore Anurag S.
Publication year - 2008
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp070338y
Subject(s) - process (computing) , pichia pastoris , space (punctuation) , biochemical engineering , computer science , scale (ratio) , design of experiments , engineering design process , design space exploration , microbiology and biotechnology , process design , product (mathematics) , process engineering , reliability engineering , engineering , mathematics , biology , mechanical engineering , process integration , physics , quantum mechanics , gene , recombinant dna , operating system , geometry , embedded system , biochemistry , statistics
The concept of “design space” has been proposed in the ICH Q8 guideline and is gaining momentum in its application in the biotech industry. It has been defined as “the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality.” This paper presents a stepwise approach for defining process design space for a biologic product. A case study, involving P. pastoris fermentation, is presented to facilitate this. First, risk analysis via Failure Modes and Effects Analysis (FMEA) is performed to identify parameters for process characterization. Second, small‐scale models are created and qualified prior to their use in these experimental studies. Third, studies are designed using Design of Experiments (DOE) in order for the data to be amenable for use in defining the process design space. Fourth, the studies are executed and the results analyzed for decisions on the criticality of the parameters as well as on establishing process design space. For the application under consideration, it is shown that the fermentation unit operation is very robust with a wide design space and no critical operating parameters. The approach presented here is not specific to the illustrated case study. It can be extended to other biotech unit operations and processes that can be scaled down and characterized at small scale.