Proposed Rules would codify FDA’s long-standing view underscoring the circumstances that justify unilateral changes to labeling by the holder of the approved application

On January 16, 2008, the Food and Drug Administration (FDA) published proposed amendments to its rules governing changes to approved applications for drugs, biologics and medical devices (the Proposed Rules). (See 73 Fed. Reg. 2848, et seq.) Specifically, the Proposed Rules would amend current FDA regulations regarding changes to an approved new drug application, biologics license application or medical device pre-market approval application in order to codify FDA’s long-standing view underscoring the circumstances that justify unilateral changes to labeling by the holder of the approved application, all before FDA formally approves a supplemental application for the labeling change. (See Id. at 2849.) The process for drugs, biologics or medical devices undergoing such a unilateral labeling change is commonly referred to as a “changes being effected supplement” or “CBE Supplement.”

To the extent that state law (e.g., state product liability laws) should require unilateral labeling changes in circumstances that do not meet CBE Supplement standards for such changes articulated by FDA in the Proposed Rules, FDA asserts that such state law requirements are preempted under the doctrine of implied conflict preemption pursuant to the Supremacy Clause of the United States Constitution. (See Id. at 2852-2853.)

The Proposed Rules are part of a greater debate respecting FDA preemption. Indeed, the question regarding whether and when FDA labeling requirements preempt state law claims is currently before the Supreme Court of the United States in three separate cases that have been accepted for review during this term. These cases include Riegel v. Medtronic (Riegal v. Medtronic, Inc. 451 F. 3d 104 (2d Cir. 2006), cert. granted, 76 USLW 3017 (June 25, 2007) (No. 06-179)) and Warner-Lambert v. Kent. (Warner-Lambert Co., LLC v. Kent, 76 USLW 3020 (September 25, 2007) (No. 06-1498). Notably, Riegal has already been argued and awaits an opinion. On January 18, 2008, the Supreme Court granted a writ of certiorari in the third case, Wyeth v. Levine. (Wyeth v. Levine, ___A.2d___, 2006 WL 3041078 (2006), cert. granted, 75 USLW 3500 (January 18, 2008) (No. 06-1249).) In all these cases, the Solicitor General, on FDA’s behalf, has weighed in strongly in favor of preemption. A central issue in this debate is whether FDA requirements simply establish a so-called compliance “floor” or whether they amount to both a “floor” and a “ceiling.” FDA has vehemently asserted the latter position, notably in the preamble to the final rule on drug labeling. (See discussion at 73 Fed. Reg. at 2849, fn. 1.)

However, proponents of the contrary view point directly to FDA’s own regulations (e.g., 21 CFR § 314.70(c)), which have been interpreted by some courts as authorizing unilateral manufacturer-initiated changes to add or strengthen warnings in virtually any circumstance on the theory that FDA’s requirements establish only a compliance “floor.” (McNellis ex rel. DeAngelis v. Pfizer, Inc., 2005 WL 3752269 (D.N.J. 2005), motion to vacate denied and interlocutory appeal certified, 2006 WL 2819046 (D.N.J. 2006), appeal pending, No. 06-5148 (3d Cir.).) Indeed, the Proposed Rules have already generated a highly critical response from the plaintiffs’ bar, which has demanded that FDA withdraw them.

In the Proposed Rules, FDA articulates a narrow view of when unilateral CBE Supplement changes are permitted. This approach closely tracks a request for an advisory opinion recently submitted to FDA. (See, Wiley Rein LLP, Request For Advisory Opinion of the Commissioner of Food and Drugs, respecting FDA interpretation of 21 C.F.R. § 314.70(c)(6)(iii), March 9, 2007.) According to the Proposed Rules, CBE Supplement changes are only authorized when “newly acquired” data provides “novel information” about the product not previously considered by FDA, “such as a risk that is different in type or severity than previously known risks about the product.” (See, e.g., 73 Fed. Reg. at 2850.) However, information that is merely “cumulative” of what was previously submitted to FDA would not justify a unilateral CBE Supplement change. To be sure, the standard for CBE Supplements might be met by “significant new analyses of previously submitted data (e.g. meta-analyses) that provide novel information about the product.” FDA has asked for comment on the circumstances when information should be considered “newly acquired” and “thus appropriate to be included in a CBE supplement.”

The Proposed Rules also reaffirm FDA’s strong rejection of hypothetical or speculative risks as proper items in labeling; FDA has stated that “[e]xaggeration of risk, or inclusion of speculative or hypothetical risks, could discourage appropriate use of a beneficial” product. (See, e.g., 73 Fed. Reg. 2851.) In this respect, over-warning could be a serious threat to the public health because of the risk of over-deterrence that it might occasion. Accordingly, and in addition to the “novelty” standard discussed above, CBE Supplement changes may only be made in accordance with the Proposed Rules “when there is sufficient evidence of a causal association” between the product and the risk.

Companies should consider filing written comments with FDA respecting the Proposed Rules. The deadline for comment submission is March 17, 2008. Moreover, companies facing questions respecting whether particular information does or does not trigger an obligation to initiate a CBE Supplement modification should contact their lawyers.

Related Links

Press release, “American Association for Justice Demands FDA Withdraw Rule Allowing Drug Companies to Claim Immunity for Failing to Warn Patients of Potential Drug Hazards”

Brief of the United States as Amicus Curiae, Wyeth v. Levine, No. 06-1249

Brief of the United Sates as Amicus Curiae Supporting Respondent, Riegel v. Medtronic, Inc., No. 06-179

Brief of the United States as Amicus Curiae Supporting Petitioners, No. 06-1498