A thorough understanding of non-mutagenic organic impurities in a drug substance and product is required for product registration along with a well-developed control strategy to ensure reproducible acceptable quality. The origin and fate of synthesis-related impurities should be investigated to establish appropriate control points in the process. Impurities originating in starting materials and reagents should also be investigated and a risk analysis performed for potential changes in the impurity profiles of materials obtained from third party sources. Knowledge of identities and conditions for formation of degradation product impurities should be obtained from forced degradation studies on drug substance and the drug formulation that represent the commercial product. Stability studies performed during earlier phases of clinical development also guide efforts for control of degradation impurities. Multiple analytical methods appropriate for impurity investigations may be necessary during development. Methods that support the proposed testing and specifications for commercial production can then be optimized for validation and routine use. The above aspects of organic impurity control for the registration phase of drug development will be discussed.
Describe the development of registration control strategies for synthesis-related impurities.
Describe forced degradation and stability studies used to understand drug degradation.
Consider potential impurities and risks of impurity profile changes in starting materials and reagents.
Describe information needed to develop appropriate registration specifications for process controls, drug substances, and drug products.