QbD-Driven PAT Applications for Precision Spray-Coating Development and Control

Wednesday, October 19, 2011: 10:20 AM
Symphony III (Hilton Minneapolis)
Charles Miller1, Bruce T. Thompson1, Fan Zhang-Plasket1, Patrick T. Schilling2, John Higgins1, Gert Thurau1, Mano Ramasamy1 and Eric Ahuja3, (1)Process Analytical Technologies, Merck and Company, Inc., West Point, PA, (2)Pharmaceutical Commercialization Technology, Merck & Co., Inc., West Point, PA, (3)Director Analytical Chemistry Development and Supply, Merck & Co, Inc, West Point, PA

Two of the core practices of Quality by Design (QbD), design space development and deployment of control strategies, can be greatly facilitated by Process Analytical Technologies (PAT). Ultimately, however, the actual usage of PAT methods for any QbD task must first be warranted by a careful and thorough risk assessment of the product, process and measurement system.

This work addresses one such case, where the product is an API-coated immediate release drug product that is manufactured by a precision spray coating process.

An initial risk assessment of the process indicated that the spray coating operation had considerable risk with respect to two critical quality attributes: content uniformity and composite assay. In response to this risk assessment, a PAT measurement system based on NIR diffuse reflectance spectroscopy was used for two different but equally critical tasks: 

1)      rapid tablet composition analysis during process development, to assist in design space development and, thus, mitigation of the content uniformity risk, and

2)      at-line monitoring of coating growth during the spray coating process, to support the spray coating control strategy, and thus mitigate the composite assay risk

Details regarding the QbD approach, as well as the design and performance of the NIR methods used for development and control, will be discussed. In addition, a brief discussion of the hardware and software infrastructure required to deploy the at-line monitoring PAT method at the supply site will be made.

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