AbbVie says it supports the FDA establishment of a public docket to assist with development of a guidance document on assessment of drug-drug interactions (DDI) for therapeutic proteins (TP). It recommends that characterization of DDIs for TPs be conducted clinically. It says that exceptions to this recommendation should only be considered and incorporated once relevant in vitro systems/preclinical models are sufficiently validated for specific DDI mechanisms. The company gives other general and specific recommendations.
GlaxoSmithKline asks FDA to refine risk classification to only “proinflammatory” cytokines or “mechanism based” TPs and to reconsider classifying non-proinflammatory agents to minimal risk.
Merck says that since publication of a 2012 FDA draft guidance, “the field has become more complex, particularly due to the development and approval of various drugs affecting the immune system beyond cytokines and cytokine modulators. Based on our assessment of the status of the field, we think that guidance in the area of pharmacokinetic therapeutic protein drug-drug interactions would be valuable, and would suggest that such guidance should not be prescriptive as the mechanistic understanding of TP-DDIs is still limited. It should also be considered that meaningful TP-DDI studies need to be conducted in patient populations, which in many cases makes study execution complex. However, general recommendations on cases where TP-DDI assessments should be considered would be valuable.”
Finally, Novartis offers comments on TPs as the perpetrator of therapeutic protein-drug interactions and TPs and low molecule weight compounds being cleared by distinctly different mechanisms.