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Pharmaceutical Industry: Manufacturing Process Reliability

Capability

Regulatory, Compliance & Quality
Technical Services

Client

A major generic pharmaceutical company

Problem

An unexplained downward shift in dissolution of a controlled release tablet placed the average dissolution result too close to the lower specification. Normal process variation caused occasional out-of-specification (OOS) results. The dissolution rate needed to be closer to the center of the desired range to prevent OOSs on this product and to assure the desired dissolution for a new combination product for which this tablet was the basis.

Approach

The client asked Tunnell to guide a joint client/Tunnell project team to resolve the problem using Tunnell’s Process Capability & Control methodology. A cross-functional approach was employed using a project manager, a formulation scientist, process engineers, statisticians, and data analysts. Batch record data was entered into a comprehensive database for over 120 batches representative of process performance. Focus interviews were conducted with key personnel from relevant levels and functions.   A detailed review of previous documentation and experimental work was completed, and detailed process observations were made. The team’s analysis pointed to changes to tablet coat weight as the cause of the process shift. The coating weight changes appeared to be caused by variability in set-up and process parameters. One-off experiments and Designs of Experiments (DoEs) were used to identify appropriate adjustments to coating set-up and other process parameters to achieve enhanced dissolution performance.

Results

Outcomes of this effort included: 

• Factors contributing to the process variation were systematically identified.
• Improvements were made to the set-up and control procedures that moved the process 
• to the desired range.
• Additional factors were identified that could be used to fine-tune the process should
• further adjustment be needed.
• The manufacturing process was improved to meet all requirements for the new
• combination product.
• Work was completed within the required time frame and budget.

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