USA – Drug mutagenicity, proarrhythmic potential addressed in pair of FDA guidances

The US Food and Drug Administration (FDA) has issued two new draft International Council on Harmonisation (ICH) guidelines for public consultation.

A question-and-answer (Q&A) guidance on clinical and nonclinical evaluation of QT/QTc interval prolongation and proarrhythmic potential of medicines was published in draft form by FDA on 29 September; the guidance is currently in ICH Step 2b, awaiting consultation from the Council’s participating countries. The draft guidelines contain Q&As addressing the ICH E14 guidance on clinical evaluation of delayed ventricular repolarization and proarrhythmic potential of non-antiarrhythmic drugs; it also includes answers to new questions regarding the ICH S7B guidance addressing nonclinical evaluation of drugs that have the potential to cause delayed ventricular repolarization.

The Q & A guides members of industry through considerations for conducting an integrated nonclinical-clinical risk assessment, “in particular, at later stages of drug development when clinical data are available,” said FDA. The Q&A also addresses such scenarios as assessing proarrhythmic and QT prolongation potential of drugs that cannot be safely administered to healthy individuals at supratherapeutic levels, and what strategies to take when placebo control is not possible…