Process Improvement in Biotech: Dealing with HighComplexity Processes
By
Hadas Artzi
Bachelor of Science in Biotechnology Engineering, Ben-Gurion University, 2005
Submitted to the MIT Sloan School of Management and the Department of Biological Engineeringin Partial Fulfillment of the Requirements for the Degrees of
Master of Business Administrationand
Master of Science in Biological Engineering
In conjunction with the Leaders for Manufacturing Program at theMassachusetts Institute of Technology
June 2009
( 2009 Massachusetts Institute of Technology. All rights reserved
MASSACHUSETTS INSTITUTEOF TECHNOLOGY
AUG 16 2 f 1
ARCHIVES
Signature of AuthorMay 8, 2009
Department of Biological EngineeringMIT Sloan School of Management
Certified byDoug1I'Lauffendurgef, Thesis Supervisor
Whitaker Professor of BioengineeringHead, Department of Biological Engineering
oy Welsch, Thesis SupervisorProfessor of Statistics and Management Science
MIT San Sc ol of Management
Alan drodzikky, GraduW Corrdmitee ChairmanDepartment of Biological Engineering
Accepted by
Accepted byDebbie Berechman, Executive Director of MBA Program
MIT Sloan School of Management
Certified by
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Process Improvement in Biotech: Dealing with High Complexity Processes
ByHadas Artzi
Submitted to the MIT Sloan School of Management and the
Department of Biological Engineering on May 8, 2009 in Partial Fulfillment of theRequirements for the Degrees of Master of Business Administration and
Master of Science in Biological Engineering
AbstractAcross numerous conventional manufacturing sites, process improvement initiatives have been
shown to increase production capabilities while decreasing costs - all without a required system-
wide overhaul of the manufacturing site. For the biotech industry, this presents an interestingchallenge. Through its upbringings as a highly interdisciplinary field, manufacturing unique biologics
poses new and complex barriers to a process improvement initiative. However, though the
challenge is daunting, process improvement in this field will in fact increase the reward two-fold.
First, as with conventional manufacturing sites, costs and lead times will decrease while potentially
increasing profits. Second, the ability to better produce more life improving drugs, and at a more
affordable price to patients is in fact a reward unto itself - one that is at the forefront of Genzyme'sculture. The turnaround process, where the manufacturing of biologics is halted in order to
maintain a key manufacturing process, is a critical point in the production of biologics. The ability
to reduce the time and variability of this process will directly and significantly increase Genzyme's
manufacturing capacity. Currently, this turnaround process takes approximately 81 days, and it is
hoped that it will be possible to attain a new turnaround time of 61 days through a number of
process improvement methodologies such as lean manufacturing. The effects of implementation of
a number of lean tools such as standardized workflow, visual management and an automation of the
pressure-hold test were studied here. Our observations reveal that by introducing lean methodology
the communication and coordination around the complex turnaround process improved, which led
to a more manageable and repeatable process. By automating the pressure-hold test it will be
possible to significantly reduce the test time and free up resources to perform additional turnaround
activities. Even with these preliminary results, it is clear that the path to process improvement at
Genzyme is possible, though not without its inherent difficulties. This work provides a critical
framework for a number of techniques used, and serves as a case study in understanding the
underlying rewards and difficulties with process improvement in the biotech industry.
Thesis Supervisor: Douglas LauffenburgerTitle: Whitaker Professor of BioengineeringHead, Department of Biological Engineering
Thesis Supervisor: Roy WelschTitle: Professor of Statistics and Management ScienceMIT Sloan School of Management
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AcknowledgmentsI would like to thank the Genzyme Corporation, and specifically the Cell Culture Operations andFacilities Engineering departments at the Allston Landing manufacturing site, for providing anextraordinary learning experience and support throughout my internship project. Special thanks to
Janani Swamy, John Calvino, Gary Foley, Doug Kennedy, Kevin Spurr and Tom Berube foraccepting me as part of their team and providing a positive and inspiring environment for myinternship. Also my gratitude to internship champion, Mark Bamforth, for sponsoring thisinternship.
I would also like to thank my thesis advisors, Douglas Lauffenburger and Roy Welsch, for giving me
invaluable advice and direction, and sharing their experiences and knowledge throughout this
project.
I would also like to acknowledge the Leaders for Manufacturing (LFM) program for providing mewith a unique internship opportunity. To the LFM staff for your help and support, my sincere
thanks. Special thanks to my peers in the LFM Class of 2009 for their support and for keepingmorale high throughout the two years of the program.
Finally, I would like to thank Alon Singer for his love, patience and support during our two yearadventure at MIT. Thank you for being there for me throughout this memorable journey and
always making me laugh.
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Table of Contents
A bstract..............................................................................................................................................................3A cknow ledgm ents .......................................................................................................................................... 5Table of Contents ........................................................................................................................--------------.... 7
List of Figures.................................................................................................................... . ---------------........ -9
List of Tables ................................................................................................................... ------------............-------- -9
1. Introduction ...................................................................................................................................... 10
1.1. Problem D efinition ................................................................................................................... 10
1.2. Com pany Background ........................................................................................................ 101.3. Biologic D rugs M anufacturing ........................................................................................ 121.4. Turnaround Process Overview ........................................................................................ 131.4.1. The Turnaround Process Improvement Initiative............................................... 151.5. Project Scope and A pproach ............................................................................................. 161.6. Thesis Overview ........................................................................................................................ 17
2. Literature Review ............................................................................................................................ 182.1. Lean and Process Improvement in the Biotech Industry.........................................182.2. Process Im provem ent Fram ew orks ............................................................................. 192.3. Overcom ing Resistance to Change ................................................................................ 212.4. Employee Communication during Change Initiatives...............................................232.5. Lean M ethodology .................................................................................................................... 242.5.1. Standard W ork ............................................................................................................... 252.5.2. V isual Process M anagem ent Tools ........................................................................... 26
3. H ypothesis.........................................................................................................................................293.1. Cycle Tim e V ariability ........................................................................................................ 293.2. Clarity of H andoffs Process ............................................................................................... 293.3. Tim e Saving O pportunities................................................................................................ 30
4. Research m ethodology ............................................................................................................. 314.1. D ata Collection .......................................................................................................................... 314.2. Fram ew ork D evelopm ent................................................................................................... 314.3. D ata A nalysis...................................................................................................
