Impurities in Oligonucleotide Drug Substances and Drug Products

被引：85

作者：

Capaldi, Daniel ^{[1
]}

Teasdale, Andy ^{[2
]}

Henry, Scott ^{[1
]}

Akhtar, Nadim ^{[2
]}

den Besten, Cathaline ^{[3
]}

Gao-Sheridan, Samantha ^{[4
]}

Kretschmer, Matthias ^{[4
]}

Sharpe, Neal ^{[5
]}

Andrews, Ben ^{[6
]}

Burm, Brigitte ^{[7
]}

Foy, Jeffrey ^{[8
]}

机构：

[1] Ionis Pharmaceut Inc, 2855 Gazelle Court, Carlsbad, CA 92010 USA

[2] AstraZeneca UK Ltd, Macclesfield, Cheshire, England

[3] ProQR Therapeut NV, Leiden, Netherlands

[4] Alnylam Pharmaceut Inc, Cambridge, MA USA

[5] Anavex Life Sci Corp, New York, NY USA

[6] GlaxoSmithKline, Stevenage, Herts, England

[7] ISA Therapeut, Leiden, Netherlands

[8] Celgene Corp, Summit, NJ USA

来源：

NUCLEIC ACID THERAPEUTICS | 2017年 / 27卷 / 06期

关键词：

oligonucleotides; impurities; identification; qualification; PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY GEL-ELECTROPHORESIS; IONIZATION MASS-SPECTROMETRY; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; INTERFERING RNA; NUCLEIC-ACIDS; THERAPEUTICS; DNA; RECOMMENDATIONS; OLIGODEOXYNUCLEOTIDES;

D O I：

10.1089/nat.2017.0691

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This white paper, which is the 10th in a series intended to address issues associated with the development of therapeutic oligonucleotides, examines the subject of product-related impurities. The authors consider chemistry and safety aspects and advance arguments in favor of platform approaches to impurity identification and qualification. Reporting, identification, and qualification thresholds suitable for product-related impurities of therapeutic oligonucleotides are proposed.

引用

页码：309 / 322

页数：14

共 55 条

[11]

Capaldi D. C., 2014, 14 ANN EUROTIDES C B

[12] Quality Aspects of Oligonucleotide Drug Development: Specifications for Active Pharmaceutical Ingredients [J].

Capaldi, Daniel ;

Ackley, Kathy ;

Brooks, Doug ;

Carmody, Judy ;

Draper, Ken ;

Kambhampati, Rao ;

Kretschmer, Matthias ;

Levin, Daren ;

McArdle, James ;

Noll, Bernhard ;

Raghavachari, Ramesh ;

Roymoulik, Ipsita ;

Sharma, B. P. ;

Thuermer, Rene ;

Wincott, Fran .

DRUG INFORMATION JOURNAL, 2012, 46 (05) :611-626

[13]

Capaldi DC, 2011, DRUGS PHARM SCI, V210, P391

[14] Formation of 4,4′-dimethoxytrityl-C-phosphonate oligonucleotides [J].

Capaldi, DC ;

Gaus, HJ ;

Carty, RL ;

Moore, MN ;

Turney, BJ ;

Decottignies, SD ;

McArdle, JV ;

Scozzari, AN ;

Ravikumar, VT ;

Krotz, AH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (18) :4683-4690

[15] Synthesis of high-quality antisense drugs. Addition of acrylonitrile to phosphorothioate oligonucleotides: Adduct characterization and avoidance [J].

Capaldi, DC ;

Gans, H ;

Krotz, AH ;

Arnold, J ;

Carty, RL ;

Moore, MN ;

Scozzari, AN ;

Lowery, K ;

Cole, DL ;

Ravikumar, VT .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (06) :832-838

[16]

Capaldi DC., 2006, 6 ANN EUROTIDES C HA

[17] Considerations for Assessment of Reproductive and Developmental Toxicity of Oligonucleotide-Based Therapeutics [J].

Cavagnaro, Joy ;

Berman, Cindy ;

Kornbrust, Doug ;

White, Tacey ;

Campion, Sarah ;

Henry, Scott .

NUCLEIC ACID THERAPEUTICS, 2014, 24 (05) :313-325

[18] Analysis of internal (n-1)mer deletion sequences in synthetic oligodeoxyribonucleotides by hybridization to an immobilized probe array [J].

Chen, DH ;

Yan, ZM ;

Cole, DL ;

Srivatsa, GS .

NUCLEIC ACIDS RESEARCH, 1999, 27 (02) :389-395

[19]

COHEN AS, 1993, J CHROMATOGR, V638, P293

[20]

Cramer H., 2013, ANAL OLIGONUCLEOTIDE, P21

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