Observations
- Inadequate understanding of process capability to remove toxic compounds.
- Carryover of toxic reagents/impurities from the Synthesis of Starting Material.
- Laboratory data is inadequate to justify the purge/removal of toxic impurities.
- Lack of understanding of the formation of toxic impurities
- Inconsistency of data from laboratory scale experiments
- Carryover of precursors that can form Genotoxic impurities including Nitrosamines
Requirement of FDA as per ICH M7
- Thorough understanding of process parameters and their impact on residual impurity levels.
- Fate and purge knowledge with sufficient confidence that the level of impurity in the drug substance will be below the acceptable limit.
- No analytical testing is recommended for this impurity. (the impurity need not need to be listed on any specification).
- A control strategy that relies on process controls with a good understanding of process chemistry.
- The risk of an impurity residing in the final drug substance above the acceptable limit is determined to be negligible.
- Justification of this control approach based on scientific principles alone is sufficient.
Solution (Services offered by Veeprho)
Mirabilis Artificial Intelligence-based risk assessment tool to assist the management of Genotoxic Impurities and their precursors.
Mirabilis generates a reactivity purge factor for the impurities based on empirical data and provides predictions for reactivity, solubility, and volatility purges.
It provides an industry-standardized approach for calculating purge factors of potentially mutagenic impurities.
A computer-assisted tool allows for a rapid, reproducible semi-quantitative measure for risk assessments of Genotoxic impurities, Nitrosamine, and their precursors.
The Final Assessment Report includes,
- The purge calculation,
- Scientific rationale
- Supporting evidence to aid in the submission to regulators.
It also helps to identify the Risk of Formation of Nitrosamines and Other Potentially Mutagenic Impurities during API Manufacturing.
This will help Drug product manufacturers to identify at-risk API prior to use, as per FDA guidelines.
Contact us for Genotoxic Assessment Services
Read more about services on Genotoxic Impurities and Nitrosamine Assessment
