FDA seems to view reverse Quality by Design or analyzing data you already have with a validated process, as both achievable and acceptable, Lundsberg-Nielsen said. The premise is that the validated product produces data that allow for improved product and process understanding, and that this information can be used to reengineer the product.
Quality by Design for a legacy product seems more complicated, time consuming and expensive than it is for a new product, and it is, said Lundsberg-Nielsen.
However, this does not mean it cant be done or that it wont provide benefits. Lundsberg-Nielsen compared the process of reverse QbD to that of an archaeological dig, in which one must peel back the layers. Historical data was available, she said, but often it had to be arduously duplicated and re-entered to be useable. Design of experiments were then set up and run on the process parameters and material attributes (not an easy process, she said).
NNE Pharmaplan studied reverse QbD with a drug-device of sorts, a wound dressing with an added API to promote healing. When the decision was made to produce the coating via continuous rather than batch processing, the products effectiveness was examined. The goal was to reduce waste and implement a control strategy to promote an in-process real-time release.
After examining historical data, the project team determined that the critical quality attributes were absorption and API content. The absorption of the product depended on the process settings. A quality risk assessment was set up where only process parameters were investigated. However, there were some internal issues within the organization, specifically with the operators, which prevented changing the speed of the process when the first design of experiments was set up.
Operators were using process speed to control the product rate, said Lundsberg-Nielsen.
The parameters the experiments were allowed to adjust were of no help with regard to out- of-spec elements. Eventually, R&D convinced the manufacturing team to allow them to run experiments over one weekend if they promised to put everything back to the existing conditions when they were done.
These new experiments proved fruitful. The team learned that the absorption qualities increased with lower mixing temperatures. In addition, yield increased by 100 percent. The end result was a dressing with better absorption qualities. Settings for the new line could thus be set up based on four process parameters.
While the new line has not been set up or validated, there is hope it will be someday. This process would have to get regulatory approval but this type of work is exactly what the agency is looking for in the Quality by Design realm, said FDA's Moheb Nasr, who was sitting in on the session. I would not call this process Quality by Re-design because people might be confused with the terminology, but it is process reengineering. More companies must be willing to share these types of examples and information to further the industry.
Lundsberg-Nielsen is not done investigating this process. Her next step is to investigate the raw materials variability.
