NDLI: Impact of Quality by Design in Process Development on the Analytical Control Strategy for a Small-Molecule Drug Substance

Content Provider	Springer Nature Link
Author	Castle, Bryan C. Forbes, Robert A.
Copyright Year	2013
Abstract	Development of the arzoxifene hydrochloride drug substance manufacturing process, first via a traditional approach and subsequently via an enhanced approach, provides an informative case study in quality by design (QbD). The primary focus of this paper is to illustrate the impact and advantages of QbD on the impurity control strategy. By operating the process at the extremes during design space studies, a larger collection of organic impurities and higher levels of typical impurities are observed in the intermediates. This enables a more thorough understanding of the ability of the process to purify the drug substance and results in a more complete and robust set of intermediate specifications as well as broader and more robust analytical methods. We demonstrate that, when each of the synthetic steps are operated within the design space, the byproduct impurities in the intermediates will not exceed levels found to be rejected in subsequent steps, ensuring that the drug substance will meet its critical quality attributes. Through the rigorous application of an enhanced process development approach, we have designed quality into the arzoxifene hydrochloride drug substance. As a result, real-time release of the intermediate batches is proposed to increase the process throughput and avoid the expense of nonvalue-added testing.
Starting Page	247
Ending Page	264
Page Count	18
File Format	PDF
ISSN	18725120
Journal	Journal of Pharmaceutical Innovation
Volume Number	8
Issue Number	4
e-ISSN	19398042
Language	English
Publisher	Springer US
Publisher Date	2013-11-08
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Arzoxifene hydrochloride Quality by design (QbD) Critical quality attribute (CQA) Enhanced process development approach Impurity control strategy Real-time release (RTR) Pharmacology/Toxicology Industrial and Production Engineering Biotechnology Biochemical Engineering
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmaceutical Science

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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