Application of the QbD Principles in the Development of the Casopitant Mesylate Manufacturing Process. Process Research Studies for the Definition of the Control Strategy of some Drug Substance-CQAs for Stages 2a, 2b, and 2c

被引：20

作者：

Cimarosti, Zadeo ^{[1
]}

Bravo, Fernando ^{[1
]}

Castoldi, Damiano ^{[1
]}

Tinazzi, Francesco ^{[1
]}

Provera, Stefano ^{[2
]}

Perboni, Alcide ^{[1
]}

Papini, Damiano ^{[1
]}

Westerduin, Pieter ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Med Res Ctr, Chem Dev, Verona, Italy

[2] GlaxoSmithKline Inc, Med Res Ctr, Mol Discovery Res, Verona, Italy

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2010年 / 14卷 / 04期

关键词：

Risk assessment - Controlled drug delivery - Design of experiments - Risk analysis - Targeted drug delivery - Drug products - Quality control;

D O I：

10.1021/op1000622

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Casopitant was identified as a potent NK(1) antagonist by GlaxoSmithKline (GSK). It was selected as part of a wide drug discovery programme within GSK for its potential activities on a number of therapeutic targets such as inflammatory bowel disease, overactive bladder, CNS disorders, and others. The mesylate salt of casopitant was selected for full development. The manufacturing process to casopitant mesylate was developed and optimised by following a Quality by Design approach, whereby a control strategy was developed, underpinned by process understanding and risk analysis, for an enhanced level of quality assurance. Quality process parameters and specifications levels for the Stages 2a, 2b, and 2c are the elements of the control strategy of the manufacturing process discussed in detail in this paper. The Design of Experiment approach has been extensively used to support the definition of the proven acceptable ranges for the process. The aim is to show the process development studies carried out to ensure quality control for the final drug substance.

引用

页码：805 / 814

页数：10

共 4 条

[1]

CIMAROSTI Z, ORG PROCESS RES DEV, DOI DOI 10.1021/OP9002X

[2] Synthesis of the NK1 Receptor Antagonist GW597599. Part 3: Development of a Scalable Route to a Key Chirally Pure Arylpiperazine Urea, A Happy End [J].

Guercio, Giuseppe ;

Bacchi, Sergio ;

Perboni, Alcide ;

Leroi, Corinne ;

Tinazzi, Francesco ;

Bientinesi, Ilaria ;

Hourdin, Marie ;

Goodyear, Michael ;

Curti, Stefano ;

Provera, Stefano ;

Cimarosti, Zadeo .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2009, 13 (06) :1100-1110

[3]

*ICHQ 10 PHARM QUA, ICH Q8 PHARM DEV ICH

[4]

*US DEP HHS FDA CD, 2004, PHARM CGMPS 21 CENT

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