Legal Memorandum: FDA's Black Box Warning for Gadolinium

Issue: What is purpose of a Food and Drug Administration (FDA) ‘Black Box Warning’ for gadolinium-based contrast agents?

Drugs that present the risk of special problems, particularly ones that may lead to death or serious injury, may be required by the FDA to have a "boxed" or "black box" warning.*FN1  This requirement is codified at 21 C.F.R. § 201.57(c), which states:

Certain contraindications or serious warnings, particularly those that may lead to death or serious injury, may be required by the FDA to be presented in a box. The boxed warning ordinarily must be based on clinical data, but serious animal toxicity may also be the basis of a boxed warning in the absence of clinical data. The box must contain, in uppercase letters, a heading inside the box that includes the word “WARNING” and conveys the general focus of the information in the box. The box must briefly explain the risk and refer to more detailed information in the “Contraindications” or “Warnings and Precautions” section, accompanied by the identifying number for the section or subsection containing the detailed information.

21 C.F.R. § 201.57(c)(1) (2014); accord id. § 201.80(e).

In May 2007, the FDA requested a black box warning for gadolinium, noting that patients with severe kidney insufficiency who receive gadolinium-based agents were at risk for developing the debilitating, and potentially fatal, disease known as nephrogenic systemic fibrosis (NSF).*FN2  The warning was last modified in December 2010.*FN3  Additional post-market safety information relating to gadolinium-based contrast agents is available […]