Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Rm. 1061

Rockville, Maryland 20852

*Re: Docket No. 2008-N-0032; Supplemental Applications Proposing
Labeling Changes for Approved Drugs, Biologics and Medical Devices.*

To Whom It May Concern:

Shook, Hardy & Bacon L.L.P. ("SHB") is pleased to submit comments in
support of the above-referenced proposed rule. SHB agrees that the
proposed rule clarifies FDA's long-standing position regarding when
changes may be made to prescription drug labeling under 21 C.F.R. §
314.70(c) (6)(iii), commonly known as the "changes being effected"
regulation. SHB further believes that the clarification is necessary
given the mischaracterization of this regulation in courts across the
country.

First, the proposed rule is consistent with FDA's long-standing
position. FDA specified as long ago as 1982 that labeling changes
pursuant to § 314.70 applied to "newly discovered risks." FDA stated
that, "some information, although still the subject of a supplement,
would no longer require agency preclearance. These supplements would
describe changes placed into effect to correct concerns about [newly
discovered risks]{.underline} from the use of the drug." 47 Fed. Reg.
46622, 46623 (FDA Oct. 19, 1982) (emphasis added); *see also id.* at
46635 (noting that changes under § 314.70 could be made to make
available "new important information about the safe use of a drug
product").

When FDA approved § 314.70 in 1985, it reiterated that this regulation
was intended to apply to newly discovered information. FDA noted that
substantive changes in labeling "are appropriately approved by FDA in
advance, unless they relate to important safety information, like a
[new]{.underline} contraindication or warning that should be immediately
conveyed to the user." 50 Fed. Reg. 7452, 7470 (FDA Feb. 22, 1985)
(emphasis added).

FDA again stated its view that § 314.70 applies to new information in
early 2006 in the preamble to "Requirements on Content and Format of
Labeling for Human Prescription Drug and Biological Products" ("the
Final Rule"). FDA noted that "\[w\]hen [new]{.underline} information
comes to light that causes information in labeling to become inaccurate,
manufacturers must act to change the content of their labeling, in
accordance with §§ 314.70 and 601.12 (21 C.F.R. 314.70 and 21 C.F.R.
601.12)." 71 Fed. Reg. 3922, 3962 (FDA Jan. 24, 2006) (emphasis added).
FDA further stated that its regulations establish "both a 'floor' and a
'ceiling,' such that additional disclosures of risk information can
expose a manufacturer to liability under the act if the additional
statement is unsubstantiated or otherwise false or misleading." *Id.* at
3935.

Finally, in December 2007, FDA stated its position that § 314.70 applied
to newly discovered information in the amicus brief filed in the Supreme
Court in *Wyeth v. Levine*, No. 06-1249. FDA noted that § 314.70 was a
narrow exception to the general rule that a manufacturer must submit a
supplemental application before making changes to a drug's labeling.
Amicus at 13. In addition, FDA noted that this exception applied to
concerns about "[newly discovered risks]{.underline}," citing its
proposed legislation in 1982. *Id.*

Despite FDA's repeated assertion that the changes being effected
regulation only applies to new risks, some courts have held otherwise,
seriously undermining FDA's authority and risking dilution of
prescription drug labeling. For instance, in *Wyeth v. Levine*, No.
2004-84, 2006 WL 3041078 (Vt. Oct. 27, 2006), the Vermont Supreme Court
interpreted § 314.70 to "allow unilateral changes to drug labels
whenever the manufacturer believes it will make the product safer."
Specifically, the court concluded:

> While specific federal labeling requirements and state common-law
> duties might otherwise leave drug manufacturers with conflicting
> obligations, 314.70(c) allows manufacturers to avoid state failure to
> warn claims without violating federal law . . . . There is thus no
> conflict between federal labeling requirements and state
> failure-to-warn claims.

*Id.* at ¶ 13 (internal citations and quotations omitted).

Other courts have reached similar conclusions. In *Caraker v. Sandoz
Pharmaceuticals*, 172 F. Supp. 2d 1018 (S.D. Ill. 2001), the Southern
District of Illinois found that the plaintiff's claim was not impliedly
preempted, stating that "after approval, additional or more forceful
warnings may, in the drug manufacturer's judgment, be added to labeling
[without prior FDA approval]{.underline} and on the drug manufacturers
own initiative." *Id.* at 1034, 1039 (emphasis in original). The Western
District of Washington likewise concluded that § 314.70 allows generic
drug manufacturers to "add or strengthen a contraindication, warning,
precaution or adverse reaction at any time without prior FDA approval."
*Laisure-Radke v. Par Pharmaceutical, Inc.*, 2006 WL 901657, at \*4-5
(W.D. Wash. Mar. 29, 2006). And in *McNellis v. Pfizer, Inc*., No.
05-1286, 2006 WL 2819046, at \*7 (D.N.J. Sep. 29, 2006), the Court
rejected the argument that § 314.70 did not allow manufacturers to
unilaterally strengthen warnings even [after]{.underline} being
presented with language from the Final Rule where FDA attempted to
clarify the intent of § 314.70.

Some courts have shown deference to FDA's statements regarding the
changes being effected regulation. In *Weiss v. Fujisawa Pharmaceutical
Co*., 464 F. Supp.2d 666 (E.D. Ky. 2006), the court recognized that
§314.70 allows drug manufacturers to warn "should they discover
[new]{.underline} evidence of a particular risk following the approval
of the original label"). *Id.* at 675; *accord*, *Perry v. Novartis
Pharmaceuticals Corp.*, 456 F. Supp.2d 678, 685-86 (E.D. Pa. 2006)
("This particular regulation was promulgated precisely to allow
drug-makers to quickly strengthen label warnings when evidence of
[new]{.underline} side effects are discovered.").

FDA's attempts to clarify the purpose of § 314.70 have been met with
mixed results. Accordingly, SHB supports FDA's clarification of its
long-standing position as set forth in Docket No. 2008-N-0032.