How do you determine genotoxic impurity limit in API?

Genotoxic impurities that are also significant metabolites may be assessed based on the acceptability of the metabolites. The concentration limits in ppm of genotoxic impurity in drug substance derived from the TTC can be calculated based on the expected daily dose to the patient using equation (1).

How do you set limits for genotoxic impurity?

The acceptable limits for daily intake of genotoxic impurities are 5, 10, 20, and 60µg/day for a duration of exposure of 6-12 months, 3-6 months, 1-3 months, and less than 1 month, respectively. For a single dose an intake of up to 120 µg is acceptable.

How pharmaceutical impurities can be identified?

Impurity identification is the process of elucidating the nature of unknown materials in pharmaceuticals, medical devices, combination products, or consumer products using a variety of analytical techniques. Sources of these impurities can come from the manufacturing process and/or storage of material.

What is meant by genotoxic impurities?

Per the International Council for Harmonization (ICH) S2 (R1) Guideline, genotoxic impurities can be broadly defined as impurities that have been demonstrated to cause deleterious changes in the genetic material regardless of the mechanism.

How big can a genotoxic impurity be detected?

Particular attention should be given to specific requirements and circumstances when validating methods used for analysis of genotoxic impurities. Developing analytical procedures for genotoxic impurities can be challenging since the procedure should allow detection limits in the range of 1 to 5ppm.

How are genotoxic impurities controlled in drug synthesis?

Controlling genotoxic impurities in drug substances and drug products The synthesis of drug substances involves the use of reagents, solvents, catalysts and other processing aids. As a result of chemical synthesis or subsequent degradation, impurities reside in all drug substances and associated drug products.

When did the ICH Guideline for genotoxic impurities start?

・ｵThe ICH steering committee approved to make ICH genotoxic impurity guideline on June 2010. ・ｵThe ICH-M7 EWG started to discuss this topic from Fukuoka, on November 2010. ・ｵICH M7 draft guideline (Step2) were completed in San Diego, on November 2012.

What are the EMA guidelines for genotoxic impurities?

The staged TTC approach is also an essential element of the EMA and FDA guidelines on genotoxic impurities.19, 20, 22. EMA Guidelines The EMA is the pioneering regulatory body that imposed detailed guidelines on how to handle genotoxic impurities.