The Experts below are selected from a list of 173286 Experts worldwide ranked by ideXlab platform
Hirokazu Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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Integrated Design of H_2O_2 Decontamination Processes and Scheduling in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2020Co-Authors: Keisho Yabuta, Haruka Futamura, Koji Kawasaki, Hirokazu SugiyamaAbstract:Purpose We explored the integrated design of H_2O_2 decontamination processes and scheduling in sterile drug Product Manufacturing, considering Productivity and Product quality. Methods Models were developed that (i) deal with the scheduling of filling and the changeover of multiple batches/Products and (ii) configure the aqueous H_2O_2 injection rate into the isolator as a process parameter. The total Production time for all planned batches and the sterility assurance level of the Products were defined as the objective functions for Productivity and Product quality, respectively. Results The models were applied to a multiobjective evaluation of the decontamination and scheduling options in the Production of 15 batches (different Products and batch sizes). Pareto-optimal solutions were obtained that indicated a trade-off between the two objectives. The inclination of the Pareto frontier increased when the Product became more vulnerable to residual H_2O_2 after aeration and when the batch size became smaller. Conclusion The quantitative results confirmed an increased impact of the configuration of the decontamination process on both Productivity and Product quality. The small batch-size Production of H_2O_2-sensitive Products is increasingly popular, especially for biopharmaceuticals, and the results of this study encourage the collaborative development of decontamination processes and Production schedules in sterile drug Product Manufacturing.
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Integrated Design of H 2 O 2 Decontamination Processes and Scheduling in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2020Co-Authors: Keisho Yabuta, Futamura Haruka, Kawasaki Koji, Hirokazu SugiyamaAbstract:We explored the integrated design of H2O2 decontamination processes and scheduling in sterile drug Product Manufacturing, considering Productivity and Product quality. Models were developed that (i) deal with the scheduling of filling and the changeover of multiple batches/Products and (ii) configure the aqueous H2O2 injection rate into the isolator as a process parameter. The total Production time for all planned batches and the sterility assurance level of the Products were defined as the objective functions for Productivity and Product quality, respectively. The models were applied to a multiobjective evaluation of the decontamination and scheduling options in the Production of 15 batches (different Products and batch sizes). Pareto-optimal solutions were obtained that indicated a trade-off between the two objectives. The inclination of the Pareto frontier increased when the Product became more vulnerable to residual H2O2 after aeration and when the batch size became smaller. The quantitative results confirmed an increased impact of the configuration of the decontamination process on both Productivity and Product quality. The small batch-size Production of H2O2-sensitive Products is increasingly popular, especially for biopharmaceuticals, and the results of this study encourage the collaborative development of decontamination processes and Production schedules in sterile drug Product Manufacturing.
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Superstructure-based process synthesis and economic assessment under uncertainty for solid drug Product Manufacturing
BMC Chemical Engineering, 2020Co-Authors: Kensaku Matsunami, Fabian Sternal, Keita Yaginuma, Shuichi Tanabe, Hiroshi Nakagawa, Hirokazu SugiyamaAbstract:This paper presents a new method for process synthesis and economic assessment for solid drug Product Manufacturing, considering continuous Manufacturing as a prominent process alternative. Of the three phases of drug development, phase II was targeted where the dosage form, formulation, and processing technology are determined. For a comprehensive alternative generation, a superstructure was developed that covered 9452 options for the unit level, which was combined with two options on the formulation strategy. The generated alternative was assessed by a net present value calculation model, which was adapted for dynamic cash flow consideration in the drug lifecycle. The model can incorporate uncertainty in the drug development and Manufacturing in the result, and can perform global sensitivity analysis by Monte Carlo simulation. The method was demonstrated in a case study where two different scenarios regarding the price of the active pharmaceutical ingredient and the demand for the Product were assumed. The results showed that when the demand and price are both low, the labor-related costs are dominant, and in the opposite case, the material-related costs become relevant. We also introduce the prototype version of the software “SoliDecision,” by which the presented method was implemented for industrial application.
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Process Model for Enhancing Yield in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2017Co-Authors: Keisho Yabuta, Masahiko Hirao, Hirokazu SugiyamaAbstract:Purpose We present a process model for enhancing the yield in the Manufacturing of sterile drug Products, such as injectables, eye drops, or intravenous bags. The process typically consists of compounding, filtration, filling, and visual inspection and involves raw materials of active pharmaceutical ingredients, water for injection, excipients, and packaging materials. Methods To define the process mathematically, we adopted the processing matrix, an approach for continuous chemical processes that enables consideration of all materials with guaranteeing mass balance. The vector- and matrix-based model was extended to describe the defect generation in the process that leads to loss of materials, such as defective Products. We also defined a path flow diagram that visualizes the defect generation paths as an aid to identify relevant root causes. Results The model was applied in a case study of an intravenous bag Manufacturing process and produced a promising idea for reducing the financially most critical defective Product. Fault tree analysis was applied to reduce the number of paths, and relevant root causes could be identified in the filling operation and in the raw material. Conclusions The developed model can serve as the basis that would replace the case-by-case approach of process improvement often observed in the industry.
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Erratum to: Decision-Support Method for the Choice Between Single-Use and Multi-Use Technologies in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2017Co-Authors: Haruku Shirahata, Masahiko Hirao, Hirokazu SugiyamaAbstract:Purpose Single-use technology has been applied to sterile drug Product Manufacturing processes as a new technology in contrast with the conventional multi-use technology. This study proposes a decision-support method for choosing between these two technologies in sterile drug Product Manufacturing.
Lesley Rushton - One of the best experts on this subject based on the ideXlab platform.
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systematic review and meta analysis of mortality in crop protection Product Manufacturing workers
Occupational and Environmental Medicine, 2009Co-Authors: David R Jones, Alex J Sutton, Keith R Abrams, J Fenty, Fiona C Warren, Lesley RushtonAbstract:Objectives: The potential health effects of the manufacture and use of crop protection chemicals were investigated through systematic review and meta-analysis of studies of cohorts of workers in the crop protection Product Manufacturing industry. Methods: Several computerised literature databases were searched from inception until December 2003, with references listed in identified articles checked for further relevant articles. Random effects meta-analyses of log standardised mortality ratios (SMRs) were carried out. Heterogeneity was explored through subgroup analyses and meta-regression; sensitivity analyses of different approaches for zero events were performed. Results: 21 references reporting information on 37 separate cohorts for mortality were identified. The meta-SMR for all cause mortality was 0.94 (95% CI 0.88 to 1.00) (37 cohorts). Significantly raised mortality was found for cancers of the buccal cavity and pharynx, oesophagus, rectum, larynx, lung, and lymphatic and haematopoietic system with little heterogeneity being observed. Excluding studies with zero events identified additional excesses. Conclusions: Evidence of multiple excesses, particularly in subgroups exposed to phenoxy herbicides contaminated with dioxins, substantiates previous findings. The importance of careful treatment of zero cases was highlighted. Future systematic reviews and meta-analyses would benefit from availability of results for a standard list of causes of disease.
Maurizio Muzzupappa - One of the best experts on this subject based on the ideXlab platform.
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application of incremental forming process for high customised medical Product Manufacturing
Journal of Materials Processing Technology, 2005Co-Authors: Giuseppina Ambrogio, L De Napoli, L Filice, Francesco Gagliardi, Maurizio MuzzupappaAbstract:Abstract Incremental Forming processes have been introduced in the recent past as an alternative to the money consuming stamping technology, when small batches have to be manufactured. Anyway, they introduce some advantages in terms of flexibility and material formability but, also, some problems such as the dimensional accuracy decreasing. In this paper, a particular application is carried out taking into account the development of an innovative technique to produce a customised ankle support. In this way Incremental Forming process has been selected for the sheet profiling, exalting the role that this technology may play when single complex Product has to be manufactured. The producing procedure finishes with a measure of the dimensional accuracy that shown a good result for the desired application.
Keisho Yabuta - One of the best experts on this subject based on the ideXlab platform.
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Integrated Design of H_2O_2 Decontamination Processes and Scheduling in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2020Co-Authors: Keisho Yabuta, Haruka Futamura, Koji Kawasaki, Hirokazu SugiyamaAbstract:Purpose We explored the integrated design of H_2O_2 decontamination processes and scheduling in sterile drug Product Manufacturing, considering Productivity and Product quality. Methods Models were developed that (i) deal with the scheduling of filling and the changeover of multiple batches/Products and (ii) configure the aqueous H_2O_2 injection rate into the isolator as a process parameter. The total Production time for all planned batches and the sterility assurance level of the Products were defined as the objective functions for Productivity and Product quality, respectively. Results The models were applied to a multiobjective evaluation of the decontamination and scheduling options in the Production of 15 batches (different Products and batch sizes). Pareto-optimal solutions were obtained that indicated a trade-off between the two objectives. The inclination of the Pareto frontier increased when the Product became more vulnerable to residual H_2O_2 after aeration and when the batch size became smaller. Conclusion The quantitative results confirmed an increased impact of the configuration of the decontamination process on both Productivity and Product quality. The small batch-size Production of H_2O_2-sensitive Products is increasingly popular, especially for biopharmaceuticals, and the results of this study encourage the collaborative development of decontamination processes and Production schedules in sterile drug Product Manufacturing.
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Integrated Design of H 2 O 2 Decontamination Processes and Scheduling in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2020Co-Authors: Keisho Yabuta, Futamura Haruka, Kawasaki Koji, Hirokazu SugiyamaAbstract:We explored the integrated design of H2O2 decontamination processes and scheduling in sterile drug Product Manufacturing, considering Productivity and Product quality. Models were developed that (i) deal with the scheduling of filling and the changeover of multiple batches/Products and (ii) configure the aqueous H2O2 injection rate into the isolator as a process parameter. The total Production time for all planned batches and the sterility assurance level of the Products were defined as the objective functions for Productivity and Product quality, respectively. The models were applied to a multiobjective evaluation of the decontamination and scheduling options in the Production of 15 batches (different Products and batch sizes). Pareto-optimal solutions were obtained that indicated a trade-off between the two objectives. The inclination of the Pareto frontier increased when the Product became more vulnerable to residual H2O2 after aeration and when the batch size became smaller. The quantitative results confirmed an increased impact of the configuration of the decontamination process on both Productivity and Product quality. The small batch-size Production of H2O2-sensitive Products is increasingly popular, especially for biopharmaceuticals, and the results of this study encourage the collaborative development of decontamination processes and Production schedules in sterile drug Product Manufacturing.
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Process Model for Enhancing Yield in Sterile Drug Product Manufacturing
Journal of Pharmaceutical Innovation, 2017Co-Authors: Keisho Yabuta, Masahiko Hirao, Hirokazu SugiyamaAbstract:Purpose We present a process model for enhancing the yield in the Manufacturing of sterile drug Products, such as injectables, eye drops, or intravenous bags. The process typically consists of compounding, filtration, filling, and visual inspection and involves raw materials of active pharmaceutical ingredients, water for injection, excipients, and packaging materials. Methods To define the process mathematically, we adopted the processing matrix, an approach for continuous chemical processes that enables consideration of all materials with guaranteeing mass balance. The vector- and matrix-based model was extended to describe the defect generation in the process that leads to loss of materials, such as defective Products. We also defined a path flow diagram that visualizes the defect generation paths as an aid to identify relevant root causes. Results The model was applied in a case study of an intravenous bag Manufacturing process and produced a promising idea for reducing the financially most critical defective Product. Fault tree analysis was applied to reduce the number of paths, and relevant root causes could be identified in the filling operation and in the raw material. Conclusions The developed model can serve as the basis that would replace the case-by-case approach of process improvement often observed in the industry.
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process systems engineering approaches for drug Product Manufacturing from tablets to injectables
2017Co-Authors: Hirokazu Sugiyama, Kensaku Matsunami, Keisho YabutaAbstract:Abstract Drug Product Manufacturing is a critical step to bring active pharmaceutical ingredient to usable forms for patients, such as tablets or injectables. This presentation showcases two recent outcomes from our research: one is on tablet Manufacturing where there is a choice between batch and continuous technologies; the other is on injectable Manufacturing where sterile environment needs to be established. The common points that both cases presented in regard to PSE was the relevance of process synthesis that supports process-oriented decision-makings in drug Product Manufacturing.
David R Jones - One of the best experts on this subject based on the ideXlab platform.
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systematic review and meta analysis of mortality in crop protection Product Manufacturing workers
Occupational and Environmental Medicine, 2009Co-Authors: David R Jones, Alex J Sutton, Keith R Abrams, J Fenty, Fiona C Warren, Lesley RushtonAbstract:Objectives: The potential health effects of the manufacture and use of crop protection chemicals were investigated through systematic review and meta-analysis of studies of cohorts of workers in the crop protection Product Manufacturing industry. Methods: Several computerised literature databases were searched from inception until December 2003, with references listed in identified articles checked for further relevant articles. Random effects meta-analyses of log standardised mortality ratios (SMRs) were carried out. Heterogeneity was explored through subgroup analyses and meta-regression; sensitivity analyses of different approaches for zero events were performed. Results: 21 references reporting information on 37 separate cohorts for mortality were identified. The meta-SMR for all cause mortality was 0.94 (95% CI 0.88 to 1.00) (37 cohorts). Significantly raised mortality was found for cancers of the buccal cavity and pharynx, oesophagus, rectum, larynx, lung, and lymphatic and haematopoietic system with little heterogeneity being observed. Excluding studies with zero events identified additional excesses. Conclusions: Evidence of multiple excesses, particularly in subgroups exposed to phenoxy herbicides contaminated with dioxins, substantiates previous findings. The importance of careful treatment of zero cases was highlighted. Future systematic reviews and meta-analyses would benefit from availability of results for a standard list of causes of disease.
