Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates
This position study provides a science-based, holistic approach to evaluating the risks of nitrosamine presence in drug-linkers as intermediates toward antibody–drug conjugate (ADC) drug substances. The evaluation of 47 different ADC drug substances, which have a recommended dose available in the pu...
Gespeichert in:
| Veröffentlicht in: | Organic process research & development 2024-08, Vol.28 (8), p.3085-3093 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3093 |
|---|---|
| container_issue | 8 |
| container_start_page | 3085 |
| container_title | Organic process research & development |
| container_volume | 28 |
| creator | Chahrour, Osama Bulger, Paul G. Dirat, Olivier Schrier, Kate Parsons, Andrew T. Ford, J. Gair Bernardoni, Frank Hetrick, Evan M. Bonaga, Llorente R. Cole, Kevin P. Miller, Joy Zhang, Qunying Jones, Michael T. |
| description | This position study provides a science-based, holistic approach to evaluating the risks of nitrosamine presence in drug-linkers as intermediates toward antibody–drug conjugate (ADC) drug substances. The evaluation of 47 different ADC drug substances, which have a recommended dose available in the public domain, supports the conclusion that the chemically synthesized fragments of ADCs are unlikely to lead to nitrosamine presence in the final drug product. Hence, it can be concluded that for most ADCs there are few nitrosamine risks introduced by the drug-linkers and their impurities. An abbreviated workflow for quality risk management of nitrosamine in drug-linkers is therefore proposed. |
| doi_str_mv | 10.1021/acs.oprd.4c00255 |
| format | Article |
| fullrecord | <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_acs_oprd_4c00255</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>c540266755</sourcerecordid><originalsourceid>FETCH-LOGICAL-a163t-6909fa6aecf91da7d4a5bca1eea84a68864e0daf24960dc8557dd871be30e7d93</originalsourceid><addsrcrecordid>eNp1kE1OwzAQhS0EEqWwZ-kDkDJOYsdZVqWUSlWRUCuxi6axU7k_dmUnSN31Cogb9iQkKltWM5r33mjmI-SRwYBBzJ6xDAN38GqQlgAx51ekx3gMEZfi87rtQSaRYAJuyV0IGwDggsU9svswYUvHX7hrsDbOUlfR-fn0PTe1dwH3xupAjaUvvllHM2O32tOprbXfa2WwbsVl0IouHJ1oq307oUNbm5VTx_Ppp0vRkbObZt1578lNhbugH_5qnyxfx4vRWzR7n0xHw1mETCR1JHLIKxSoyypnCjOVIl-VyLRGmaKQUqQaFFZxmgtQpeQ8U0pmbKUT0JnKkz6By96y_SF4XRUHb_bojwWDoqNVtLSKjlbxR6uNPF0inbJxjbftgf_bfwGkZXK4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates</title><source>ACS Publications</source><creator>Chahrour, Osama ; Bulger, Paul G. ; Dirat, Olivier ; Schrier, Kate ; Parsons, Andrew T. ; Ford, J. Gair ; Bernardoni, Frank ; Hetrick, Evan M. ; Bonaga, Llorente R. ; Cole, Kevin P. ; Miller, Joy ; Zhang, Qunying ; Jones, Michael T.</creator><creatorcontrib>Chahrour, Osama ; Bulger, Paul G. ; Dirat, Olivier ; Schrier, Kate ; Parsons, Andrew T. ; Ford, J. Gair ; Bernardoni, Frank ; Hetrick, Evan M. ; Bonaga, Llorente R. ; Cole, Kevin P. ; Miller, Joy ; Zhang, Qunying ; Jones, Michael T.</creatorcontrib><description>This position study provides a science-based, holistic approach to evaluating the risks of nitrosamine presence in drug-linkers as intermediates toward antibody–drug conjugate (ADC) drug substances. The evaluation of 47 different ADC drug substances, which have a recommended dose available in the public domain, supports the conclusion that the chemically synthesized fragments of ADCs are unlikely to lead to nitrosamine presence in the final drug product. Hence, it can be concluded that for most ADCs there are few nitrosamine risks introduced by the drug-linkers and their impurities. An abbreviated workflow for quality risk management of nitrosamine in drug-linkers is therefore proposed.</description><identifier>ISSN: 1083-6160</identifier><identifier>EISSN: 1520-586X</identifier><identifier>DOI: 10.1021/acs.oprd.4c00255</identifier><language>eng</language><publisher>American Chemical Society</publisher><ispartof>Organic process research & development, 2024-08, Vol.28 (8), p.3085-3093</ispartof><rights>2024 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a163t-6909fa6aecf91da7d4a5bca1eea84a68864e0daf24960dc8557dd871be30e7d93</cites><orcidid>0009-0009-8682-4986 ; 0000-0003-0419-647X ; 0000-0002-2333-6557 ; 0009-0008-0474-8485 ; 0000-0002-0320-0919</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.oprd.4c00255$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.oprd.4c00255$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids></links><search><creatorcontrib>Chahrour, Osama</creatorcontrib><creatorcontrib>Bulger, Paul G.</creatorcontrib><creatorcontrib>Dirat, Olivier</creatorcontrib><creatorcontrib>Schrier, Kate</creatorcontrib><creatorcontrib>Parsons, Andrew T.</creatorcontrib><creatorcontrib>Ford, J. Gair</creatorcontrib><creatorcontrib>Bernardoni, Frank</creatorcontrib><creatorcontrib>Hetrick, Evan M.</creatorcontrib><creatorcontrib>Bonaga, Llorente R.</creatorcontrib><creatorcontrib>Cole, Kevin P.</creatorcontrib><creatorcontrib>Miller, Joy</creatorcontrib><creatorcontrib>Zhang, Qunying</creatorcontrib><creatorcontrib>Jones, Michael T.</creatorcontrib><title>Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates</title><title>Organic process research & development</title><addtitle>Org. Process Res. Dev</addtitle><description>This position study provides a science-based, holistic approach to evaluating the risks of nitrosamine presence in drug-linkers as intermediates toward antibody–drug conjugate (ADC) drug substances. The evaluation of 47 different ADC drug substances, which have a recommended dose available in the public domain, supports the conclusion that the chemically synthesized fragments of ADCs are unlikely to lead to nitrosamine presence in the final drug product. Hence, it can be concluded that for most ADCs there are few nitrosamine risks introduced by the drug-linkers and their impurities. An abbreviated workflow for quality risk management of nitrosamine in drug-linkers is therefore proposed.</description><issn>1083-6160</issn><issn>1520-586X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kE1OwzAQhS0EEqWwZ-kDkDJOYsdZVqWUSlWRUCuxi6axU7k_dmUnSN31Cogb9iQkKltWM5r33mjmI-SRwYBBzJ6xDAN38GqQlgAx51ekx3gMEZfi87rtQSaRYAJuyV0IGwDggsU9svswYUvHX7hrsDbOUlfR-fn0PTe1dwH3xupAjaUvvllHM2O32tOprbXfa2WwbsVl0IouHJ1oq307oUNbm5VTx_Ppp0vRkbObZt1578lNhbugH_5qnyxfx4vRWzR7n0xHw1mETCR1JHLIKxSoyypnCjOVIl-VyLRGmaKQUqQaFFZxmgtQpeQ8U0pmbKUT0JnKkz6By96y_SF4XRUHb_bojwWDoqNVtLSKjlbxR6uNPF0inbJxjbftgf_bfwGkZXK4</recordid><startdate>20240816</startdate><enddate>20240816</enddate><creator>Chahrour, Osama</creator><creator>Bulger, Paul G.</creator><creator>Dirat, Olivier</creator><creator>Schrier, Kate</creator><creator>Parsons, Andrew T.</creator><creator>Ford, J. Gair</creator><creator>Bernardoni, Frank</creator><creator>Hetrick, Evan M.</creator><creator>Bonaga, Llorente R.</creator><creator>Cole, Kevin P.</creator><creator>Miller, Joy</creator><creator>Zhang, Qunying</creator><creator>Jones, Michael T.</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0009-0009-8682-4986</orcidid><orcidid>https://orcid.org/0000-0003-0419-647X</orcidid><orcidid>https://orcid.org/0000-0002-2333-6557</orcidid><orcidid>https://orcid.org/0009-0008-0474-8485</orcidid><orcidid>https://orcid.org/0000-0002-0320-0919</orcidid></search><sort><creationdate>20240816</creationdate><title>Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates</title><author>Chahrour, Osama ; Bulger, Paul G. ; Dirat, Olivier ; Schrier, Kate ; Parsons, Andrew T. ; Ford, J. Gair ; Bernardoni, Frank ; Hetrick, Evan M. ; Bonaga, Llorente R. ; Cole, Kevin P. ; Miller, Joy ; Zhang, Qunying ; Jones, Michael T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a163t-6909fa6aecf91da7d4a5bca1eea84a68864e0daf24960dc8557dd871be30e7d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chahrour, Osama</creatorcontrib><creatorcontrib>Bulger, Paul G.</creatorcontrib><creatorcontrib>Dirat, Olivier</creatorcontrib><creatorcontrib>Schrier, Kate</creatorcontrib><creatorcontrib>Parsons, Andrew T.</creatorcontrib><creatorcontrib>Ford, J. Gair</creatorcontrib><creatorcontrib>Bernardoni, Frank</creatorcontrib><creatorcontrib>Hetrick, Evan M.</creatorcontrib><creatorcontrib>Bonaga, Llorente R.</creatorcontrib><creatorcontrib>Cole, Kevin P.</creatorcontrib><creatorcontrib>Miller, Joy</creatorcontrib><creatorcontrib>Zhang, Qunying</creatorcontrib><creatorcontrib>Jones, Michael T.</creatorcontrib><collection>CrossRef</collection><jtitle>Organic process research & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chahrour, Osama</au><au>Bulger, Paul G.</au><au>Dirat, Olivier</au><au>Schrier, Kate</au><au>Parsons, Andrew T.</au><au>Ford, J. Gair</au><au>Bernardoni, Frank</au><au>Hetrick, Evan M.</au><au>Bonaga, Llorente R.</au><au>Cole, Kevin P.</au><au>Miller, Joy</au><au>Zhang, Qunying</au><au>Jones, Michael T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates</atitle><jtitle>Organic process research & development</jtitle><addtitle>Org. Process Res. Dev</addtitle><date>2024-08-16</date><risdate>2024</risdate><volume>28</volume><issue>8</issue><spage>3085</spage><epage>3093</epage><pages>3085-3093</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>This position study provides a science-based, holistic approach to evaluating the risks of nitrosamine presence in drug-linkers as intermediates toward antibody–drug conjugate (ADC) drug substances. The evaluation of 47 different ADC drug substances, which have a recommended dose available in the public domain, supports the conclusion that the chemically synthesized fragments of ADCs are unlikely to lead to nitrosamine presence in the final drug product. Hence, it can be concluded that for most ADCs there are few nitrosamine risks introduced by the drug-linkers and their impurities. An abbreviated workflow for quality risk management of nitrosamine in drug-linkers is therefore proposed.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.oprd.4c00255</doi><tpages>9</tpages><orcidid>https://orcid.org/0009-0009-8682-4986</orcidid><orcidid>https://orcid.org/0000-0003-0419-647X</orcidid><orcidid>https://orcid.org/0000-0002-2333-6557</orcidid><orcidid>https://orcid.org/0009-0008-0474-8485</orcidid><orcidid>https://orcid.org/0000-0002-0320-0919</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1083-6160 |
| ispartof | Organic process research & development, 2024-08, Vol.28 (8), p.3085-3093 |
| issn | 1083-6160 1520-586X |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_acs_oprd_4c00255 |
| source | ACS Publications |
| title | Risk Evaluation of N‑Nitrosamines in Drug-Linker Intermediates Used To Generate Antibody–Drug Conjugates |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T14%3A27%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Risk%20Evaluation%20of%20N%E2%80%91Nitrosamines%20in%20Drug-Linker%20Intermediates%20Used%20To%20Generate%20Antibody%E2%80%93Drug%20Conjugates&rft.jtitle=Organic%20process%20research%20&%20development&rft.au=Chahrour,%20Osama&rft.date=2024-08-16&rft.volume=28&rft.issue=8&rft.spage=3085&rft.epage=3093&rft.pages=3085-3093&rft.issn=1083-6160&rft.eissn=1520-586X&rft_id=info:doi/10.1021/acs.oprd.4c00255&rft_dat=%3Cacs_cross%3Ec540266755%3C/acs_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |