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PHARMACEUTICAL INDUSTRY :
Manufacturing Process Improvement |
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Client: |
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A major generic pharmaceutical company
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Problem: |
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About six months after launch, an unexplained shift in a release parameter occurred. As a result, over the next two years, approximately one-third of the batches were out of specification and had to be discarded. Numerous investigations had been conducted without identifying a root cause, and changes to processing conditions did not return the manufacturing process to its previous performance.
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Approach: |
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The client asked Tunnell to investigate and resolve the problem. A cross-functional approach was employed using a joint client/Tunnell project team that included a project manager, a formulation scientist, process engineers, statisticians, and data analysts. Batch record data was entered into a comprehensive database for over 40 batches representing good and bad process performance. Focus interviews were conducted with key personnel from relevant levels and functions. A detailed review of previous investigations and documents was completed, and detailed process observations were made. A screening DoE was conducted to test hypotheses. The data analysis and screening DoE pointed to changes to tablet coating characteristics as the cause of the process shift. In a follow-up project, designed experiments were conducted, which confirmed this hypothesis and successfully identified process conditions that would allow production of batches that consistently met specification and performed similarly to batches produced during development and the period immediately after launch.
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Results: |
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Outcomes
of this effort included:
Key process variables were identified.
Factors contributing to the process variation were systematically
identified.
Data-driven analysis along with iterative technical insight were
employed to develop a model of the factors responsible for the observed
dissolution variability.
Optimization experimental designs and confirmatory trials were
executed and process changes were identified to return the process
to acceptable performance.
Work was completed within the required time frame and budget.
The client’s capability to supply the market was improved.
The client’s capability to supply the market was improved.
Through the joint team approach, Tunnell’s problem solving
methods were transferred to key client personnel.
Expected savings from a reduction in discarded batches are estimated
at $2.8M/yr.
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