Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
In the risk assessment of impurities in pharmaceutical products, a basic approach is to identify and quantify each impurity, and to assess the toxicity of each impurity substance, and establish quality standards based on acceptable intake levels such as PDE. In addition to side reactants and degradation products, impurities in raw materials and excipients, the leachables from container closure systems or equipment used in manufacturing may also be included as impurities in final products. In particular, most of leachables are industrial chemicals, for which little toxicity information is available, it is difficult to assess the toxicity of individual substances. Therefore, it is necessary to manage risks by setting control thresholds based on the TTC (Threshold of Toxicological Concern) approach, which enables comprehensive risk management for small amount of chemical exposure. The TTC approach has been applied not only to the threshold setting for genotoxic carcinogens, but also to the threshold setting for non-genotoxicity. The original non-genotoxic TTCs have been adopted in the evaluation of food flavors, and extended to apply the assessment of leachables from food containers and apparatus. However, the toxicity information used in threshold settings for such non-genotoxic effects is mostly based on toxicity results from oral exposure studies. Therefore, threshold settings essentially apply only to impurities in oral drug formulations. On the other hand, parenteral drug products are considered to have a higher risk of exposure to leachables from container closure systems and manufacturing facilities than oral drug products. I would like to discuss how toxicity data from oral exposure experiments should be applied to the assessment of extractables and leachables from intravenous administered drug products and inhaled drug products etc.
