This document is intended to guide concerning the Quality [that is (i.e.), Chemistry and Manufacturing] portion of NDSs and ANDSs for drug substances of synthetic or semi-synthetic origin and their related drug products that are filed with Health Canada under Division C.08 of the Food and Drug Regulations. The purpose of the guidance document is to outline the Quality technical requirements and to assist submission sponsors in preparing the NDS or ANDS to ensure an effective and efficient assessment process. It can also be used as guidance on the requirements for related drug submissions [for example (e.g.), Supplemental New Drug Submissions (SNDSs), Supplemental Abbreviated New Drug Submissions (SANDSs), and Post-Notice of Compliance (NOC) Changes].
S.3.2. Impurities:
Potential impurities should be examined for structural alert(s). Assessment and control of any potentially mutagenic impurities, including the potential formation or introduction of high- potency mutagenic carcinogens identified in the ICH M7 guideline as the cohort of concern (comprising aflatoxin-like, N-nitroso and alkyl-azoxy compounds) should be performed as per ICH M7 when appropriate. The ability of the related substances analytical method(s) used to detect and control potential impurities (e.g. intermediates) should be discussed (e.g. including potential impurities that would be controlled as unspecified impurities in the final drug substance specifications).
S.4.1 Specifications:
The drug substance specification should include routine testing for nitrosamine impurities when the risk for presence is high or the concentration of any nitrosamine is at significant levels (for example, greater than 30% of the acceptable intake limit).
P.2. Pharmaceutical Development:
A summary and discussion should be provided of the following:
- the measures taken during development to mitigate the presence of high- potency mutagenic
carcinogens identified in the ICH M7 guideline as the cohort of concern (comprising aflatoxin-like, N-nitroso and alkyl-azoxy compounds) in the drug product and its components - a risk assessment for the potential presence of nitrosamine impurities in the drug product - provided in sections 2.3 and 3.2.P.2 of the drug application
Health Canada - Quality (chemistry and manufacturing) draft guidance.pdf (1.1 MB)