a process analytical technology (pat) approach to control a new api manufacturing process development, validation and implementa文档.doc

A Process Analytical Technology (PAT) approach to control a new API manufacturing process Development, validation and implementa A Process Analytical Technology (PAT) approach to control a new APImanufacturing process: Development, validation and implementationCédric Schaefera,d,n, David Clicqa, Clémence Lecomteb, Alain Merschaertb,Edith Norrantc, Frédéric FotiadudaUCB Pharma, Analytical Development Chemicals, Avenue de l’Industrie, 1420 Braine-l’Alleud, BelgiumbUCB Pharma, Chemical Process Development, Avenue de l’Industrie, 1420 Braine-l’Alleud, BelgiumcUCB Pharma, Innovation & Technology Development, Avenue de l’Industrie, 1420 Braine-l’Alleud, BelgiumdInstitut des Sciences Moléculaires de Marseille, CNRS, UMR 7313, école Centrale Marseille, Aix Marseille Université, Avenue Escadrille Normandie-Niemen,Case A62, 13397 Marseille cedex 20, Francea r t i c l e i n f oArticle history:Received 27 May 2013Received in revised form19 November 2013Accepted 26 November 2013Available online 2 December 2013Keywords:Process Analytical Technology (PAT)Quality-by-Design (QbD)Near infrared spectroscopyAPI crystallizationIn-process control (IPC)Method validationa b s t r a c tPharmaceutical companies are progressively adopting and introducing Process Analytical Technology(PAT) and Quality-by-Design (QbD) concepts promoted by the regulatory agencies, aiming the building ofthe quality directly into the product by combining thorough scientific understanding and quality riskmanagement. An analytical method based on near infrared (NIR) spectroscopy was developed as a PATtool to control on-line an API (active pharmaceutical ingredient) manufacturing crystallization stepduring which the API and residual solvent contents need to be precisely determined to reach thepredefined seeding point. An original methodology based on the QbD principles was designed to conductthe development and validation of the NIR method and to ensure that it is fitted for its intended use. Onthis ba