464713 Considerations in Developing a Control Strategy for Continuous Direct Compression

Tuesday, November 15, 2016: 3:59 PM
Continental 4 (Hilton San Francisco Union Square)
Donald Kientzler1, Aditya Vanarase2, Anthony Tantuccio3, Kevin Macias4, Timothy Stevens5, Admassu Abebe6, Alexander Schaepman7 and James Holman7, (1)Process R&D, Bristol-Myers Squibb Company, New Brunswick, NJ, (2)Drug Product Science and Technology, Bristol-Myers Squibb, New Brunswick, NJ, (3)BMS, New Brunswick, NJ, (4)Bristol-Myers Squibb, New Brunswick, NJ, (5)Biopharmaceutics Process Analytical Sciences, Bristol-Myers Squibb Company, New Brunswick, NJ, (6)Bristol Myers Squibb Co, (7)GEA, Wommelgem, Belgium

In this work a continuous direct compression (CDC) process was investigated for a low dose drug product for an API with cohesive material properties. The CDC process was developed on the GEA CDC-50 system. A risk based approach was followed during the entire process development of CDC. The process parameters for feeding and blending were selected such that the feeding variability is sufficiently filtered by the available residence time distribution (RTD) of the blending system. The holistic control strategy for CDC involved specifications for input materials, in-process controls for various drug product attributes including blend concentration, tablet weight and hardness, and a product release strategy. The blend concentration was monitored using an in-line NIR method and a RTD model of the CDC line as two redundant methods. In the event when the blend concentration falls outside the given specification limits, non-conforming tablets were diverted. For using the RTD model as a process monitoring method, sensitivity of RTD model to material variability and method of feed rate measurement were identified as the main risks. In this presentation, the development studies conducted to address these risks will be discussed. In addition the pros and cons of using each process monitoring method as well as considerations in designing a diversion system will be discussed.

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