FDA Finalizes ICH M7 Guidance on Mutagenic Carcinogens
Regulatory News | 13 March 2018 |
The US Food and Drug Administration (FDA) on Tuesday finalized ICH’s guidance on DNA-reactive substances that could potentially cause damage when present at low levels and potentially cause cancer.
“This final guidance provides guidance on acceptable intake limits derived for some chemicals that are considered to be mutagenic carcinogens and are also commonly used in the synthesis of pharmaceuticals or are useful examples to illustrate the principles for deriving for deriving compound-specific intakes described in ICH M7,” FDA said.
The agency’s finalization of the guidance follows the ICH Assembly’s and regulatory agencies’ endorsement of it in June 2017.
The 131-page guidance document features sections on considerations for marketed products, drug substance and drug product impurity assessments, hazard assessment elements, risk characterization, control, documentation and three appendices on scenarios for the application of ICH M7, case examples to illustrate potential control approaches and an addendum to M7.
For drugmakers, the guidance can help inform the development of new drug substances and new drug products during their clinical development and subsequent marketing applications.
“The default method from ICH M7 of linear extrapolation from the cancer potency estimate, TD50 is used as the primary method to derive the acceptable intakes for carcinogens with likely mutagenic mode of action,” FDA said. “After consideration of the comments received, hydroxylamine monograph was deleted from the final guidance. Relevant editorial changes were also made to improve clarity and to incorporate the ICH M7(R1) Addendum guidance.”
M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk Guidance for Industry
“This final guidance provides guidance on acceptable intake limits derived for some chemicals that are considered to be mutagenic carcinogens and are also commonly used in the synthesis of pharmaceuticals or are useful examples to illustrate the principles for deriving for deriving compound-specific intakes described in ICH M7,” FDA said.
The agency’s finalization of the guidance follows the ICH Assembly’s and regulatory agencies’ endorsement of it in June 2017.
The 131-page guidance document features sections on considerations for marketed products, drug substance and drug product impurity assessments, hazard assessment elements, risk characterization, control, documentation and three appendices on scenarios for the application of ICH M7, case examples to illustrate potential control approaches and an addendum to M7.
For drugmakers, the guidance can help inform the development of new drug substances and new drug products during their clinical development and subsequent marketing applications.
“The default method from ICH M7 of linear extrapolation from the cancer potency estimate, TD50 is used as the primary method to derive the acceptable intakes for carcinogens with likely mutagenic mode of action,” FDA said. “After consideration of the comments received, hydroxylamine monograph was deleted from the final guidance. Relevant editorial changes were also made to improve clarity and to incorporate the ICH M7(R1) Addendum guidance.”
M7(R1) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals To Limit Potential Carcinogenic Risk Guidance for Industry
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