Generic Narrow Therapeutic Index Drugs: Challenges faced by the FDA

By Dr Nicola Davies

In November 2022, the US Food and Drug Administration (FDA) hosted a webinar on the topic Understanding Generic Narrow Therapeutic Index (NTI) Drugs. The aim of the webinar was to educate healthcare professionals on NTI drugs and the FDA’s efforts to ensure therapeutic equivalence of generic NTI drugs.1

‘NTI drug’ is a term used to describe any therapy where small differences in dosing may lead to serious therapeutic failures or adverse drug reactions. Examples include warfarin, lithium carbonate, levothyroxine, tacrolimus, and cyclosporine. To obtain FDA approval, generic NTIs are expected to be therapeutically equivalent to the brand product, with pharmaceutical equivalence in terms of containing the same active pharmaceutical ingredients in the same concentration, dosage, and route of administration. While inactive ingredients such as binders and preservatives may be different in some cases, the FDA requires adequate evidence to show that these inactive ingredients in the generic drug do not affect its safety, efficacy, and quality.2