{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/111489"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/111489","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Modeling drug substance purification manufacturing through schedule optimization and simulation","abstract":"This thesis develops a method by which overtime could be reduced in a highly variable drug substance purification manufacturing environment. Purification production overtime (20%) is a big cost driver at Building XX1 (BXX). Current production planning and labor resource evaluation methods at BXX Purification are manual, do not capture schedule delays, and do not adequately account for labor availability. Because of this, BXX is unable to accurately evaluate to what extent labor resource contributes to bottlenecking or how to improve overtime. A tool is devised in the Virtually Exhaustive Combinatorial System (VirtECS®) Scheduler software whereby purification production schedules are modeled and optimized. The model simulates production delays and the flow of production. Results lead to a more accurate understanding of how labor resource constrains the lot cycle time and where improvements in shift structure could be made to improve lot cycle time and variability of lot cycle time. The purification production schedules of two monoclonal antibodies (mAb) were modeled with the use of VirtECS® Scheduler. These two drug substances are selected to reflect the majority of BXX's mAb pipeline. The plant, BXX, produces a high mix of clinical and commercial launch drug substances, and is subject to a number of stochastic scheduling delays. Excel® is used to generate random sets of process times to simulate delays. These process times are fed into VirtECS®, a production schedule optimization tool, which then produces a simulated set of production schedules. Scheduling decisions of shift labor allocation and when manufacturing should start production during the week are simulated using the model. Results from this evaluation illustrate opportunities for BXX to improve overtime. Lot cycle time is found to be reduced by up to 5.9% based on model results by moving the start of production towards the end of the week and allocating more resources to the third shift from second shift. Additionally, cycle time variability, could be reduced by up to 22%. The model makes a number of assumptions which simplify purification operations whose effect should be further investigated. Future improvements for VirtECS® are proposed to better model BXX processes.","abstract_html":"This thesis develops a method by which overtime could be reduced in a highly variable drug substance purification manufacturing environment. Purification production overtime (20%) is a big cost driver at Building XX1 (BXX). Current production planning and labor resource evaluation methods at BXX Purification are manual, do not capture schedule delays, and do not adequately account for labor availability. Because of this, BXX is unable to accurately evaluate to what extent labor resource contributes to bottlenecking or how to improve overtime. A tool is devised in the Virtually Exhaustive Combinatorial System (VirtECS®) Scheduler software whereby purification production schedules are modeled and optimized. The model simulates production delays and the flow of production. Results lead to a more accurate understanding of how labor resource constrains the lot cycle time and where improvements in shift structure could be made to improve lot cycle time and variability of lot cycle time. The purification production schedules of two monoclonal antibodies (mAb) were modeled with the use of VirtECS® Scheduler. These two drug substances are selected to reflect the majority of BXX's mAb pipeline. The plant, BXX, produces a high mix of clinical and commercial launch drug substances, and is subject to a number of stochastic scheduling delays. Excel® is used to generate random sets of process times to simulate delays. These process times are fed into VirtECS®, a production schedule optimization tool, which then produces a simulated set of production schedules. Scheduling decisions of shift labor allocation and when manufacturing should start production during the week are simulated using the model. Results from this evaluation illustrate opportunities for BXX to improve overtime. Lot cycle time is found to be reduced by up to 5.9% based on model results by moving the start of production towards the end of the week and allocating more resources to the third shift from second shift. Additionally, cycle time variability, could be reduced by up to 22%. The model makes a number of assumptions which simplify purification operations whose effect should be further investigated. Future improvements for VirtECS® are proposed to better model BXX processes.","abstract_has_math":false,"creators":["McIntire, Seth (Seth Cullen)"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Leaders for Global Operations Program at MIT","school":null,"contributors":[],"advisors":["Donald B. Rosenfield and Stanley Gershwin."],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017","date_published":"2017","updated_at":"2026-07-22T22:21:18Z","subjects":["Sloan School of Management.","Mechanical Engineering.","Leaders for Global Operations Program."],"languages":["eng"],"rights":["MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/111489","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Donald B. 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They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/111489"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis: M.B.A., Massachusetts Institute of Technology, Sloan School of Management, in conjunction with the Leaders for Global Operations Program at MIT, 2017.","Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, in conjunction with the Leaders for Global Operations Program at MIT, 2017.","Cataloged from PDF version of thesis.","Includes bibliographical references (pages 35-36)."]},{"key":"dc:description.abstract","label":"Abstract","values":["This thesis develops a method by which overtime could be reduced in a highly variable drug substance purification manufacturing environment. Purification production overtime (20%) is a big cost driver at Building XX1 (BXX). Current production planning and labor resource evaluation methods at BXX Purification are manual, do not capture schedule delays, and do not adequately account for labor availability. Because of this, BXX is unable to accurately evaluate to what extent labor resource contributes to bottlenecking or how to improve overtime. A tool is devised in the Virtually Exhaustive Combinatorial System (VirtECS®) Scheduler software whereby purification production schedules are modeled and optimized. The model simulates production delays and the flow of production. Results lead to a more accurate understanding of how labor resource constrains the lot cycle time and where improvements in shift structure could be made to improve lot cycle time and variability of lot cycle time. The purification production schedules of two monoclonal antibodies (mAb) were modeled with the use of VirtECS® Scheduler. These two drug substances are selected to reflect the majority of BXX's mAb pipeline. The plant, BXX, produces a high mix of clinical and commercial launch drug substances, and is subject to a number of stochastic scheduling delays. Excel® is used to generate random sets of process times to simulate delays. These process times are fed into VirtECS®, a production schedule optimization tool, which then produces a simulated set of production schedules. Scheduling decisions of shift labor allocation and when manufacturing should start production during the week are simulated using the model. Results from this evaluation illustrate opportunities for BXX to improve overtime. Lot cycle time is found to be reduced by up to 5.9% based on model results by moving the start of production towards the end of the week and allocating more resources to the third shift from second shift. Additionally, cycle time variability, could be reduced by up to 22%. The model makes a number of assumptions which simplify purification operations whose effect should be further investigated. Future improvements for VirtECS® are proposed to better model BXX processes."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["M.B.A.","S.M."]},{"key":"dc:title","label":"Title","values":["Modeling drug substance purification manufacturing through schedule optimization and simulation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Donald B. Rosenfield and Stanley Gershwin."],"dc:contributor.department":["Leaders for Global Operations Program at MIT","Massachusetts Institute of Technology. Department of Mechanical Engineering","Sloan School of Management"],"dc:contributor.other":["Leaders for Global Operations Program."],"dc:creator":["McIntire, Seth (Seth Cullen)"],"dc:date.accessioned":["2017-09-15T15:36:26Z"],"dc:date.available":["2017-09-15T15:36:26Z"],"dc:date.issued":["2017"],"dc:description":["Thesis: M.B.A., Massachusetts Institute of Technology, Sloan School of Management, in conjunction with the Leaders for Global Operations Program at MIT, 2017.","Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, in conjunction with the Leaders for Global Operations Program at MIT, 2017.","Cataloged from PDF version of thesis.","Includes bibliographical references (pages 35-36)."],"dc:description.abstract":["This thesis develops a method by which overtime could be reduced in a highly variable drug substance purification manufacturing environment. Purification production overtime (20%) is a big cost driver at Building XX1 (BXX). Current production planning and labor resource evaluation methods at BXX Purification are manual, do not capture schedule delays, and do not adequately account for labor availability. Because of this, BXX is unable to accurately evaluate to what extent labor resource contributes to bottlenecking or how to improve overtime. A tool is devised in the Virtually Exhaustive Combinatorial System (VirtECS®) Scheduler software whereby purification production schedules are modeled and optimized. The model simulates production delays and the flow of production. Results lead to a more accurate understanding of how labor resource constrains the lot cycle time and where improvements in shift structure could be made to improve lot cycle time and variability of lot cycle time. The purification production schedules of two monoclonal antibodies (mAb) were modeled with the use of VirtECS® Scheduler. These two drug substances are selected to reflect the majority of BXX's mAb pipeline. The plant, BXX, produces a high mix of clinical and commercial launch drug substances, and is subject to a number of stochastic scheduling delays. Excel® is used to generate random sets of process times to simulate delays. These process times are fed into VirtECS®, a production schedule optimization tool, which then produces a simulated set of production schedules. Scheduling decisions of shift labor allocation and when manufacturing should start production during the week are simulated using the model. Results from this evaluation illustrate opportunities for BXX to improve overtime. Lot cycle time is found to be reduced by up to 5.9% based on model results by moving the start of production towards the end of the week and allocating more resources to the third shift from second shift. Additionally, cycle time variability, could be reduced by up to 22%. The model makes a number of assumptions which simplify purification operations whose effect should be further investigated. Future improvements for VirtECS® are proposed to better model BXX processes."],"dc:description.degree":["M.B.A.","S.M."],"dc:identifier.uri":["http://hdl.handle.net/1721.1/111489"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Sloan School of Management.","Mechanical Engineering.","Leaders for Global Operations Program."],"dc:title":["Modeling drug substance purification manufacturing through schedule optimization and simulation"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:21:18Z"}