(176c) Quality by Design and Design Space Enabling Continuous Improvements for a Commercial Solid Oral Drug Product

The purpose of this presentation is to demonstrate the risk management approach used in development of a commercial product filed using the Quality by Design and Design Space concepts during the FDA pilot program. The Critical Quality Attribute (CQA) identified through our Right First Time risk assessment work process clearly defined the product design space. With a successful launch campaign, the product demand exceeded the original forecasts. The manufacturing site was challenged to streamline processing to maximize production rates while maintaining quality.

In this presentation, we discuss two aspects for improvements in process efficiencies which demonstrate how commercial manufacturing translated the output of the risk management approach to significant cost savings and waste material reductions. First, a spike in the tablet potency at the end of the compression was revealed during technology transfer and determined to occur when 300 grams remained in the press (enough only to fill the die channels). The existing controls on the equipment allowed press shut-off to be automatically set at approximately 1.5 - 2 kg blend remaining in the press. Commercial manufacturing projects reduced the blend discharged quantity from ~1.5 - 2 kg to NLT 0.5 kg per batch, and resulted in significant cost savings in terms of improved efficiency, and reduced waste. The second efficiency improvement discussed here was aimed at eliminating a bottleneck in the film coating process by scaling up from 115 to 350kg. Two theoretical film coating models were employed to establish the process parameters that matched the smaller scale coating process using a design space approach, and thus eliminated the need for large scale trials. The final process produced quality product at the recommended operating ranges. These continuous improvement efforts resulted in a robust drug product process. These accomplishments are attributed to the Quality by Design and Continuous Improvement approaches utilized in the development and commercialization of this product.