By James M. Beck, Senior Life Sciences Policy Analyst with Reed Smith LLP in its Philadelphia, PA office, and founder of, and a regular contributor to, the award-winning Drug and Device Law blog.

In 2006 the Food and Drug Administration overhauled drug labeling and created a new section called “Highlights.”  See 21 C.F.R. § 201.57(a) (specifying highlights section requirements).  Such highlights must include “[a] concise summary of any boxed warning.”  §201.57(a)(4).  With respect to all other warnings, contraindications, and adverse reactions, the highlights regulation provides:

(9) Contraindications.  A concise statement of each of the product’s contraindications, as required under paragraph (c)(5) of this section, with any appropriate subheadings.

(10) Warnings and precautions.  A concise summary of the most clinically significant information required under paragraph (c)(6) of this section, with any appropriate subheadings, including information that would affect decisions about whether to prescribe a drug, recommendations for patient monitoring that are critical to safe use of the drug, and measures that can be taken to prevent or mitigate harm.

(11) Adverse reactions.

(i) A list of the most frequently occurring adverse reactions, as described in paragraph (c)(7) of this section, along with the criteria used to determine inclusion (e.g., incidence rate).  Adverse reactions important for other reasons . . . must not be repeated under this heading in Highlights if they are included elsewhere in Highlights. . . .

21 C.F.R. § 201.57(a)(9-11) (emphasis added).

The FDA’s final rule adopting the regulation described the Highlights section:

[T]he final rule requires that the labeling for new and more recently approved products include introductory information entitled “Highlights of Prescribing Information” (Highlights) (§§201.56(d)(1) and 201.57(a)).

The final rule requires the same headings for Highlights as proposed, except that, in response to comments, FDA moved “Most Common Adverse Reactions” from “Warnings and Precautions” (proposed §201.57(a)(10)) to a new heading entitled “Adverse Reactions” (§§201.56(d)(1) and 201.57(a)(11)).  Like the proposed rule, the final rule requires that Highlights, except for the boxed warning, be limited in length to one-half of the page (§ 201.57(d)(8)) (see comment 104).

The agency is also revising its regulations on supplements and other changes to an approved application in §§314.70 and 601.12 (21 CFR 314.70 and 601.12) to require applicants to obtain prior approval of any labeling changes to Highlights, except for identified minor changes (see comment 5).

Requirements on Content & Format of Labeling for Human Prescription Drug and Biological Products, 71 Fed. Reg. 3299, 3925 (FDA Jan. 24, 2006) (emphasis added).