Impurities in Oligonucleotide Drug Substances and Drug Products

被引：78

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
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
[J]. 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
Capaldi, DC
Gaus, HJ
Carty, RL
Moore, MN
Turney, BJ
Decottignies, SD
McArdle, JV
Scozzari, AN
Ravikumar, VT
Krotz, AH
[J]. 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
Capaldi, DC
Gans, H
Krotz, AH
Arnold, J
Carty, RL
Moore, MN
Scozzari, AN
Lowery, K
Cole, DL
Ravikumar, VT
[J]. 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
Cavagnaro, Joy
Berman, Cindy
Kornbrust, Doug
White, Tacey
Campion, Sarah
Henry, Scott
[J]. 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
Chen, DH
Yan, ZM
Cole, DL
Srivatsa, GS
[J]. NUCLEIC ACIDS RESEARCH, 1999, 27 (02) : 389 - 395
[19] COHEN AS, 1993, J CHROMATOGR, V638, P293
[20] Cramer H., 2013, ANAL OLIGONUCLEOTIDE, P21

← 1 2 3 4 5 6 →