title: Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.
abstract: Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product.
authors: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903. Electronic address: sherif.badawy@bms.com.
authors: Sherif I F
authors: SI
authors: Badawy
authors: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Ajit S
authors: AS
authors: Narang
authors: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Keirnan R
authors: KR
authors: LaMarche
authors: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Ganeshkumar A
authors: GA
authors: Subramanian
authors: Drug Product Science and Technology, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Sailesh A
authors: SA
authors: Varia
authors: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Judy
authors: J
authors: Lin
authors: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Tim
authors: T
authors: Stevens
authors: Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903.
authors: Pankaj A
authors: PA
authors: Shah
mesh_terms: D000268:Adhesiveness; D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000592:standards; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D065546:Drug Liberation; D004349:Drug Packaging; D004355:Drug Stability; D010316:Particle Size; D011786:Quality Control; D012995:Solubility; D019265:Spectroscopy, Near-Infrared; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards*; D014227:Triazines / Q000737:chemistry* / Q000592:standards
chemical_list: D013608:Tablets, Enteric-Coated; D014227:Triazines; C509922:brivanib; D000409:Alanine
keywords: brivanib alaninate; control strategy; critical material attributes; critical process parameters; critical quality attributes; design space; dissolution; porosity; quality by design; tablets