[Federal Register Volume 65, Number 52 (Thursday, March 16, 2000)]
[Notices]
[Pages 14286-14288]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-6422]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0222]


Decision in Washington Legal Foundation v. Henney

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: In the Federal Register of August 12, 1999 (64 FR 44025), the 
Food and Drug Administration (FDA) published in its entirety an order 
entitled ``Final Amended Order Granting Summary Judgment and Permanent 
Injunction.'' The order was entered by the United States District Court 
for the District of Columbia in Washington Legal Foundation v. Henney, 
56 F. Supp. 2d 81 (1999). The Court of Appeals subsequently vacated the 
district court decision and injunction (and earlier decisions and 
injunctions) insofar as they declared unconstitutional (1) Statutory 
provisions concerning the dissemination by manufacturers of certain 
written materials concerning new uses of approved products (21 U.S.C. 
360aaa et seq.), and (2) an FDA guidance document concerning certain 
industry-supported scientific and educational activities known 
generally as industry-supported continuing medical education or 
``CME.'' Washington Legal Foundation v. Henney, No. 99-5304, 2000 WL 
122099, slip op. (D.C. Cir. Feb. 11, 2000). Consequently, these 
statutory provisions now constitute a ``safe harbor'' for manufacturers 
that comply with them; the CME guidance document details how the agency 
intends to exercise its enforcement discretion. FDA, consistent with 
its longstanding interpretation of the laws it administers, may 
proceed, in the context of case-by-case enforcement, to determine from 
a manufacturer's written materials and activities how it intends that 
its products be used. The Court of Appeals also recognized that if the 
agency brings an enforcement action, a manufacturer may raise a First 
Amendment defense.

FOR FURTHER INFORMATION CONTACT:
    Regarding biological products and devices regulated by the Center 
for Biologics Evaluation and Research: Toni M. Stifano, Center for 
Biologics Evaluation and Research (HFM-600), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-6190.
    Regarding human drug products: Laurie B. Burke, Center for Drug 
Evaluation and Research (HFD-40), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-2828.
    Regarding medical devices: Byron L. Tart, Center for Devices and 
Radiological Health (HFZ-302), Food and Drug Administration, 2098 
Gaither Rd., Rockville, MD 20850, 301-594-4639.

SUPPLEMENTARY INFORMATION: The Federal Food, Drug, and Cosmetic Act of 
1938 (FDCA), as amended, generally prohibits the manufacturer of a new 
drug or medical device \1\ from distributing a product in interstate 
commerce for any intended use that FDA has not approved as safe and 
effective. The intended use or uses of a drug or device may be set 
forth in, among other things, its label or ``labeling,'' which includes 
written, printed, or graphic matter affixed to or ``accompanying'' the 
product. See 21 U.S.C. 321(m); 21 CFR 202.1(l)(2); see also 21 CFR 
201.128, 801.4. The intended use or uses of a drug or device may also 
be determined from advertisements, promotional material, oral 
statements by the product's manufacturer or its representatives, and 
any other relevant source. Action on Smoking and Health v. Harris, 655 
F.2d 236, 239 (D.C. Cir. 1980); see also 21 CFR 201.128 and 801.4.
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    \1\ For purposes of this notice, the terms ``drug or medical 
device'' include biologic products regulated under section 351(a) of 
the Pubic Health Service Act.
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    When FDA approves a drug or medical device, the agency approves the 
product for each use set out in the product's approved labeling. A use 
that FDA approves is thus sometimes referred to as an ``approved'' or 
``labeled'' use. A use that does not appear in the labeling is not 
approved as safe and effective by FDA and is known as an ``unapproved'' 
or ``off-label'' use. In this notice, such a use is referred to as a 
``new use.''
    A central feature of the FDCA is that it generally prohibits 
interstate commerce in new drugs and devices for ``new uses.'' In 
particular, the statute provides that ``[n]o person shall introduce or 
deliver for introduction into interstate commerce any new drug, unless 
an approval of an application filed pursuant to [21 U.S.C. Sec. 355(b) 
or (j)] is effective with respect to such drug.'' 21 U.S.C. 355(a); see 
21 U.S.C. 331(d). Such an application must identify the particular use 
or uses to which the new drug will be put, and an approval of such an 
application for interstate distribution can become effective only with 
respect to such use(s). See 21 U.S.C. 355(b), (d), (j). Thus, an 
approved new drug that is marketed for a ``new use'' becomes an 
unapproved new drug with respect to that use.
    An approved new drug that is marketed for a ``new use'' is also 
``misbranded'' under the FDCA, because the labeling of such a drug 
would not include ``adequate directions for use.'' 21 U.S.C. 352(f); 
see United States v. Articles of Drug * * * Rucker Pharmacal Co., 625 
F.2d 665, 673 (5th Cir. 1980). Similarly, a medical device that is 
distributed for a ``new use'' is ``adulterated,'' see 21 U.S.C. 351(f), 
and ``misbranded,'' see 21 U.S.C. 352(f). An adulterated or misbranded 
product is prohibited from distribution in interstate commerce (21 
U.S.C. 331(a), (k)), as is a drug that is marketed for a ``new use'' 
(21 U.S.C. 331(d)).
    An approved new drug that is marketed for a ``new use'' may be 
seized (because it is an unapproved new drug with respect to that use), 
as may an adulterated or misbranded new drug or device (21 U.S.C. 334), 
and the government may seek an injunction against, or criminal 
prosecution of,

[[Page 14287]]

those responsible for introducing such a product into commerce (21 
U.S.C. 332, 333).
    Section 401 of the Food and Drug Administration Modernization Act 
of 1997 (FDAMA or section 401), 21 U.S.C. 360aaa et seq., amended the 
FDCA. It describes certain conditions under which a drug or device 
manufacturer may choose to disseminate to physicians and other health 
care practitioners certain written materials discussing a ``new use'' 
of its product. If those conditions are met, the government may not use 
that dissemination as evidence of the manufacturer's intent that its 
product be used for a new use. See 21 U.S.C. 360aaa-6(b). If section 
401 did not exist, the government could use such dissemination as 
evidence in establishing a manufacturer's illegal distribution of a new 
drug or device for a ``new use,'' and in establishing that the product 
is misbranded or, in the case of a device, adulterated as well as 
misbranded.
    Prior to FDAMA, FDA articulated its policy concerning the promotion 
of ``new uses'' in three guidance documents. FDAMA and its implementing 
regulations superseded the two guidance documents that addressed the 
dissemination of written ``new use'' information (reprints and 
reference texts) by drug and medical device manufacturers. See 61 FR 
52800-52801 (October 8, 1996). FDAMA does not affect the third guidance 
document (the CME guidance document), which identifies 12 factors that 
the agency will consider in determining whether a manufacturer, through 
its support of scientific and educational activities, evidenced a ``new 
use'' of its drugs or devices. See 62 FR 64093-64100 (December 3, 
1997).
    Washington Legal Foundation presented a First Amendment challenge 
to section 401 and the three guidance documents. The district court 
issued orders declaring FDAMA, its implementing regulations, and the 
guidance documents unconstitutional. Among other things, the district 
court, with a number of qualifications, enjoined FDA from ``in any way 
* * * limit[ing] any pharmaceutical or medical device manufacturer'' 
from ``disseminating'' specified journal articles or medical texts and 
from ``suggesting content or speakers'' to an ``independent program 
provider'' in connection with a seminar or symposium funded by the 
manufacturer. See Washington Legal Foundation v. Henney, 56 F. Supp. 2d 
81, 88-89 (D.D.C. 1999); Washington Legal Foundation v. Friedman, 36 
F. Supp. 2d 16, 18-19 (D.D.C. 1999); Washington Legal Foundation v. 
Friedman, 13 F. Supp. 2d 51, 74-75 (D.D.C. 1998).
    On February 11, 2000, the Court of Appeals for the District of 
Columbia Circuit vacated the district court's decisions and injunctions 
insofar as they declared section 401 and the CME guidance document 
unconstitutional. See slip op. at 10. (The other two guidance 
documents, pertaining to the dissemination of certain written materials 
about ``new uses,'' had been superseded by FDAMA and its implementing 
regulations and were not at issue in the Court of Appeals.)
    The D.C. Circuit's decision was based on its conclusion that there 
is no case or controversy to provide a basis for WLF's facial First 
Amendment challenge. In reaching that conclusion, the court relied on 
the government's interpretation that (1) Section 401 provides a ```safe 
harbor' ensuring that certain forms of conduct [will] not be used 
against manufacturers in misbranding and `intended use' enforcement 
actions'' based on pre-FDAMA enforcement authority (slip op. at 8), 
discussed above, and (2) neither FDAMA nor the CME Guidance Document 
``independently authorizes the FDA to prohibit or sanction speech'' 
(id.). Put another way, if a manufacturer follows the provisions of 
FDAMA and its implementing regulations (21 CFR part 99), including, but 
not limited to, its provision concerning the submission of a 
supplemental application for FDA approval of a ``new use,'' FDA may not 
use the information disseminated by the manufacturer as evidence that 
the product is intended to be used for a ``new use.'' If a manufacturer 
proceeds under section 401 and its implementing regulations but does 
not comply, FDA may seek to enforce compliance through an injunction 
action under the FDCA to halt a violation of section 301(z). If a 
manufacturer does not proceed under section 401, that failure does not 
constitute an independent violation of law.
    FDA traditionally has recognized the important public policy 
reasons to permit industry support for the full exchange of views in 
scientific and educational discussions, including discussions of ``new 
uses.'' FDA has distinguished between those activities supported by 
manufacturers that are nonpromotional and otherwise independent from 
the substantive influence of the supporting manufacturer and those that 
are not. Those activities that have been deemed by the agency to be 
independent from influence by the supporting manufacturer and 
nonpromotional have not been treated as labeling or advertising, and 
have not been subjected to the agency's regulatory scrutiny. Under the 
CME guidance document, FDA does not expect to treat industry-supported 
CME any differently than it traditionally has done. If a manufacturer 
does not follow the CME guidance document, that, by itself, is not an 
independent violation of law. Slip op. at 8.
    Plaintiff Washington Legal Foundation (WLF) expressly agreed that 
FDA may proceed on a case-by-case basis under pre-FDAMA enforcement 
authority. See e.g., Washington Legal Foundation v. Henney, No. 99-
5304, Transcript of Oral Argument, January 10, 2000 (TR.) at 43, 58, 
75; see Washington Legal Foundation v. Henney, slip op. at 7, 8, and 9. 
Nonetheless, WLF urged the D.C. Circuit to reach the merits of the 
district court's decisions and injunctions on the ground that FDA 
``will prosecute manufacturers for violating a normative standard'' set 
forth in FDAMA or the CME Guidance Document. Slip op. at 9. The 
appellate court declined, finding that there was no constitutional 
controversy between the parties that remained to be resolved and that 
ruling on the constitutionality of a hypothetical interpretation of the 
statute would be inappropriate. Id. at 10. In vacating the district 
court's decisions and injunctions insofar as they declared FDAMA and 
the CME Guidance Document unconstitutional, the D.C. Circuit noted that 
a manufacturer may, of course, argue that FDA's use of the 
manufacturer's promotion of a ``new use'' as evidence in a particular 
enforcement action violates the First Amendment. Slip op. at 9, n. 6.
    In sum, then, FDAMA and its implementing regulations constitute a 
``safe harbor'' for a manufacturer that complies with them before and 
while disseminating journal articles and reference texts about ``new 
uses'' of approved products. If a manufacturer does not comply, FDA may 
bring an enforcement action under the FDCA, and seek to use journal 
articles and reference texts disseminated by the manufacturer as 
evidence that an approved product is intended for a ``new use.'' 
Manufacturers that support CME may wish to become familiar with the CME 
guidance document, which details the factors FDA intends to take into 
account in exercising its enforcement discretion in relation to 
industry-supported scientific and educational activities. The CME 
guidance document, however, does not itself have the force and effect 
of law.

[[Page 14288]]

References

    The following references are on display in the Dockets Management 
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852, and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.
    1. Washington Legal Foundation v. Henney, No. 99-5304, 2000 WL 
122099, slip op. (D.C. Cir. February 11, 2000).
    2. Washington Legal Foundation v. Henney, No. 99-5304, transcript 
of oral argument, January 10, 2000.

    Dated: March 9, 2000.
Jane E. Henney,
Commissioner of Food and Drugs.
[FR Doc. 00-6422 Filed 3-10-00; 4:15 pm]
BILLING CODE 4160-01-F