Impulse mixer technology reliability and redesign improvement in biotechnology drug substance manufacturing

Objective: In place of traditional stainless steel systems, the "Flexible Manufacturing" technology used at Amgen employs the impulse mixer single-use system, a bag technology, to house the product and serve as the locale for biological reactions. However, the impulse mixers have experienced high failure rates. About 14% of impulse mixers have failed, and these failures jeopardized $10 M of raw materials; they have also delayed manufacturing production by at least 12 days. This thesis identifies the root causes for the impulse mixer failure and proposes recommendations to reduce future failures. Methods: Semi-structured interviews (n=12) were conducted with system designers and with operators using the impulse mixer. A kaizen event to discuss impulse mixer failure was conducted for three days with ten key stakeholders from all manufacturing plants. A survey was implemented to gather and assess operators' perspectives (n=12) on the impulse mixer technology. Furthermore, quantitative data about 101 impulse mixers used from July 2013 to October 2015 were collected from all manufacturing sites. Qualitative methods were used to develop key themes from the semi-structured interviews and kaizen event around root causes, and statistical analysis of the quantitative data and survey were performed to identify and verify root causes. Hypotheses: The study proposes four hypotheses concerning impulse mixer failure: 1) preparatory training protocol changes will decrease the odds that impulse mixer single-use technology will fail; 2) operational training tools change will decrease the odds that impulse mixer single-use technology will fail; 3) operator's knowledge and confidence decrease as the operators are farther removed from interacting with the supplier, and 4) the plastic material's lack of strength influences impulse mixer technology to fail. Results: On the job training on the floor by the supplier to manufacturing operators (operational training) demonstrated to be very impactful in decreasing failure. Supplier, operational training of how to install the bag technology, is statistically significantly related (p<0.005) to the likelihood that the impulse mixer would fail. The odds of failure were about 1 in 6 for the first operational training. In contrast, in a third operational training the odds of failure dropped to about 1 in 220. Recommendations: The supplier needs to provide more training to the manufacturing operators in how to install the technology. More interaction between the supplier and operator will decrease the technology failures in the floor. At the moment, there is a very complex system for operators to acquire information from the supplier, making it difficult for operators to acquire information when they needed it. A leaner system where the interaction is direct is needed.

Department dc:contributor.department

Leaders for Global Operations Program at MIT

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2016

Author dc:creator

• Mota, J. Guadalup O. (J. Guadalupe Ocegueda)

Advisor dc:contributor.advisor

• Arnold Barnett and Bruce Cameron.

• Sloan School of Management.
• Institute for Data, Systems, and Society.
• Engineering Systems Division.
• Leaders for Global Operations Program.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/104553

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/104553