FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

Congressional research reportMar 19, 2009

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FDA Guidance Regarding the Promotion of

Off-Label Uses of Drugs: Legal Issues

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March 19, 2009

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Prepared for Members and Committees of Congress

FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

Summary

New drugs may not be introduced or marketed without the approval of the Food and Drug

Administration (FDA). When a person submits a drug application to the FDA for approval, the

application includes samples of the proposed labeling. The FDA may refuse to approve an

application if the drug is not safe or effective for the specific uses that are reflected in its labeling.

An unapproved new use of a drug, also known as an off-label use, is a use not mentioned in the

drug’s approved labeling. Although a physician may prescribe a drug for off-label uses, a

pharmaceutical manufacturer may not market or promote uses of a drug other than those on the

label—those uses approved by the FDA in the application.

In January 2009, the FDA issued a guidance document on the dissemination of medical

information regarding off-label uses of drugs. The guidance seemingly creates a safe harbor for

dissemination of information on off-label uses of FDA-approved drugs and medical devices.

However, the agency’s guidance statement does not have the force or effect of law, and the FDA

still retains its legal authority under the Federal Food, Drug, and Cosmetic Act (FFDCA) and

FDA regulations to determine when promotion of an unapproved new use has occurred or when a

product is misbranded. Additionally, the guidance does not affect the legal authority, enforcement

powers, or other capabilities of outside entities that have been involved in prosecuting False

Claims Act (FCA) cases related to off-label marketing and the submission of false claims for

reimbursement from the U.S. government.

First, this report outlines the relevant provisions of the FFDCA and related regulations that have

been used to address misbranding violations of the act that relate to pharmaceutical

manufacturers’ promotion of off-label use. Second, the report summarizes the FDA’s previous offlabel marketing provisions under the FDA Modernization Act of 1997 (FDAMA), which are no

longer in effect. Third, the report details the January 2009 guidance document and its similarities

to and differences from the FDAMA provisions. Fourth, the report outlines First Amendment

challenges to FDAMA and older FDA guidance documents addressing off-label promotion. Fifth,

the report discusses the nature of guidance documents, in contrast to rules promulgated under the

Administrative Procedure Act (APA), as well as administrative law issues associated with the

FDA’s issuance of the guidance. Sixth, the report provides an overview of the FCA and related

qui tam cases that addressed off-label marketing practices of pharmaceutical companies. Finally,

the report analyzes the interaction of the new guidance document and the FCA.

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

Contents

FDA Laws, Regulations, and Guidance Documents on Off-Label Use........................................... 1

Relevant Provisions of the Federal Food, Drug, and Cosmetic Act and Related

Regulations ............................................................................................................................. 1

The FDA Modernization Act’s Off-Label Marketing Provisions .............................................. 3

Legislative History .............................................................................................................. 5

The FDA’s January 2009 Guidance ........................................................................................... 6

Administrative Law Issues............................................................................................................... 8

Rules and Guidance Documents ................................................................................................ 8

Is the Guidance a Substantive Rule Subject to a Notice-and-Comment Rulemaking? ............. 9

Does the FDA Have the Authority to Issue the Guidance? ............................................... 10

First Amendment Challenges ......................................................................................................... 12

False Claims Act Issues ................................................................................................................. 16

The False Claims Act............................................................................................................... 16

False Claims Act Cases Involving Off-Label Promotion ........................................................ 16

Interaction of the FDA Guidance with the False Claims Act .................................................. 19

Contacts

Author Contact Information........................................................................................................... 22

Acknowledgments ......................................................................................................................... 22

Congressional Research Service

FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

n January 13, 2009, the Food and Drug Administration (FDA) issued a notice in the

Federal Register regarding the availability of its guidance for industry on the distribution

of medical journal articles and scientific publications regarding unapproved new uses

(also known as off-label uses) of approved drugs.1 The guidance seemingly creates a safe harbor

for dissemination of information on off-label uses of FDA-approved drugs.2 The FDA’s guidance

contains provisions similar to, and potentially more expansive than, the provisions on

dissemination of information on off-label uses in § 401 of the FDA Modernization Act of 1997

(FDAMA), which expired in 2006. No similar provision was included in the most recent piece of

major FDA legislation, the FDA Amendments Act of 2007 (FDAAA).

First, this report outlines the relevant provisions of the Federal Food, Drug, and Cosmetic Act

(FFDCA) and related regulations that have been used to address misbranding violations of the act

that relate to pharmaceutical manufacturers’ promotion of off-label use. Second, the report

summarizes the FDA’s previous off-label marketing provisions under FDAMA § 401, which are

no longer in effect. Third, the report details the January 2009 guidance document and its

similarities to and differences from the FDAMA provisions. Fourth, the report outlines First

Amendment challenges to FDAMA and older FDA guidance documents addressing off-label

promotion.3 Fifth, the report discusses the nature of guidance documents, in contrast to rules

promulgated under the Administrative Procedure Act (APA), as well as administrative law issues

associated with the FDA’s issuance of the guidance. Sixth, the report provides an overview of the

False Claims Act (FCA) and related qui tam4 cases that addressed off-label marketing practices of

pharmaceutical companies. Finally, the report analyzes the interaction of the new guidance

document and the FCA.

FDA Laws, Regulations, and Guidance Documents

on Off-Label Use

Relevant Provisions of the Federal Food, Drug, and Cosmetic Act

and Related Regulations

Until the FDA has approved a new drug pursuant to either a new drug application, an abbreviated

new drug application, or an investigational new drug submission, the new drug may not be

“introduc[ed] or deliver[ed] for introduction into interstate commerce.”5 When a person submits a

new drug application to the FDA for approval, the application includes samples of the proposed

Guidance for Industry on Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or

Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical

Devices, 74 Fed. Reg. 1694 (Jan. 13, 2009) [hereinafter Guidance Notice].

While the guidance applies to FDA-approved drugs and medical devices, this report focuses on drugs, as it appears

the majority of False Claims Act suits relate to the unlawful promotion of off-label use of prescription drugs.

See FDA, Guidance for Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical

or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical

Devices, Guidance, http://www.fda.gov/oc/op/goodreprint.html [hereinafter Guidance].

“Qui tam is short for ‘qui tam pro domino rege quam pro se ipso in hac parte sequitur,’ which means ‘who pursues

this action on our Lord the King’s behalf as well as his own.’” Rockwell Int’l Corp. v. United States, 549 U.S. 457 n.2

(2007).

21 U.S.C. § 355(a).

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

labeling for the drug.6 The FDA may refuse to approve a new drug application if the HHS

Secretary finds, among other possibilities, that it is not safe or effective “for use under the

conditions prescribed, recommended, or suggested in the proposed labeling.”7 In other words, the

FDA approves drugs for specific uses that are reflected in their labeling. An unapproved use of a

drug, also known as an off-label use, has been defined as a “use for indication, dosage form, dose

regimen, population [i.e., the drug is approved for adults but not children] or other use parameter

not mentioned in the approved labeling.”8 While a physician may prescribe a drug for off-label

uses,9 a pharmaceutical manufacturer may not market or promote a drug for uses other than those

on the label—those uses approved by the FDA in a drug application.10 Off-label uses have been

estimated to account for 21% of all prescription drug use.11

Manufacturer marketing and promotion of off-label uses is linked to the FFDCA’s prohibition

against misbranding.12 The concept of misbranding is one of the basic components of the

FFDCA, and persons who violate the act’s prohibitions are subject to criminal and civil penalties,

as well as injunctions and seizures of the misbranded product. A drug or device shall be deemed

to be misbranded if, among other possibilities, the labeling is false or misleading13 or if its

labeling does not bear “adequate directions for use.”14

The phrase “adequate directions for use” means “directions under which the layman can use a

drug safely and for the purposes for which it is intended.”15 An “intended use,” in turn, “refer[s]

to the objective intent of the persons legally responsible for the labeling of drugs,” such as the

drug’s manufacturer, and that person’s objective intent may be shown by “labeling claims,

21 U.S.C. § 355(b)(1)(F).

21 U.S.C. § 355(d).

FDA, Janet Woodcook, A Shift in the Regulatory Approach (June 1997), slide 3, http://www.fda.gov/cder/present/

diamontreal/regappr/sld001.htm.

“Allowing physicians to prescribe drugs for such ‘off-label’ usage ‘is an accepted and necessary corollary of the

FDA’s mission to regulate [pharmaceuticals] without directly interfering with the practice of medicine.” United States

ex rel. Franklin v. Warner-Lambert Co., 147 F. Supp. 2d 39 (D. Mass. 2001) (quoting Buckman Co. v. Plaintiffs’ Legal

Comm., 531 U.S. 341 (2001)). See also Medicare Part B, which provides coverage for certain off-label uses of

approved drugs. Section 1861(t) of The Social Security Act, 42 U.S.C. § 1395x(t); FDA, supra note 8, at slides 4-5.

See 21 U.S.C. § 331(a), (d); Washington Legal Foundation v. Henney, 202 F.3d 331, 333 (D.C. Cir. 2000); Franklin,

147 F. Supp. 2d at 44.

Anna Wilde Mathews and Avery Johnson, Boost for Off-Label Drug Use—FDA Would Let Firms Keep Doctors

Informed on Unapproved Methods, Wall St. J., Feb. 16, 2008, at A3.

See 21 U.S.C. § 331(a) (prohibiting “[t]he introduction or delivery for introduction into interstate commerce of any ...

drug [or] device . . . that is adulterated or misbranded”); 21 U.S.C. § 331(d) (prohibiting “[t]he introduction or delivery

for introduction into interstate commerce of any article in violation of section ... 505 [approval of new drug

applications]”); 21 U.S.C. §§ 331(c), (k) (prohibiting the receipt and delivery or proffered delivery of misbranded drugs

and devices as well as “the doing of any other act while such [drug or device] is held for sale ... after shipment in

interstate commerce [that] results in such article being adulterated or misbranded”).

21 U.S.C. § 352(a).

21 U.S.C. § 352(f)(1).

21 C.F.R. § 201.5. There are exemptions from “adequate directions for use,” but the exemption for prescription drugs

still requires the drug’s labeling to “bear[] adequate information for its use, including indications, effects ... and

precautions under which practitioners licensed by law to administer the drug can use the drug safely and for the

purposes for which it is intended, including all purposes for which it is advertised or represented; and ... the labeling

bearing such information is the labeling authorized by the approved new drug application.” 21 C.F.R. § 201.100(c).

The labeling in such a case must contain “adequate information for such use ... [in] the same language and emphasis as

labeling approved and permitted, under the provisions of section 505 [new drug applications], and any other parts of the

labeling are consistent with and not contrary to such approved or permitted labeling.” 21 C.F.R. § 201.100(d).

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

advertising matter, or oral or written statements by such persons or their representatives.”16

Intended use may also “be shown by the circumstances that the article is, with the knowledge of

such persons or their representatives, offered and used for a purpose for which it is neither labeled

nor advertised.”17 Manufacturers are “required to provide adequate labeling for” off-label uses of

a drug that the “manufacturer knows, or has knowledge of facts that would give him notice that

[the] drug ... is to be used for conditions, purposes, or uses other than the ones for which he offers

it.”18 It appears then that, if a drug manufacturer promotes an intended use that is an off-label use,

the drug’s label will not bear adequate directions for use and will thus be a misbranded drug.19 A

drug manufacturer would therefore be required to submit a supplemental new drug application for

that off-label use and accompanying label or dosage changes.20

The FFDCA defines labeling as “all labels and other written, printed or graphic matters (1) upon

any article or any of its containers or wrappers, or (2) accompanying such article.”21 Labeling

includes brochures, motion picture films, and literature, as well as

reprints and similar pieces of printed, audio, or visual matter descriptive of a drug and

references published (for example, the ‘Physician’s Desk Reference’) for use by medical

practitioners, pharmacists, or nurses, containing drug information supplied by the

manufacturer, packer, or distributor of the drug and which are disseminated by or on behalf

of its manufacturer, packer, or distributor.22

It appears that a reprint of an article published in a medical journal that is presented to a doctor by

a pharmaceutical representative could fall within the FFDCA’s labeling provisions and

accompanying regulations.

The FDA Modernization Act’s Off-Label Marketing Provisions

Before Congress passed the Food and Drug Administration Modernization Act (FDAMA) in

1997, the FDA had issued several guidance documents regarding off-label promotion in 1996

regarding the industry’s dissemination of reprints and reference texts.23 FDAMA § 401

superceded those guidance documents and generally enabled manufacturers to disseminate

information about new, or off-label, uses under specified conditions, but only if the manufacturer

submitted a supplemental new drug application for the off-label use.24 FDAMA § 401 expired on

21 C.F.R. § 201.128.

Id.

Based on 21 C.F.R. § 201.128, it appears that if the manufacturer learns that the drug is being used off-label, that the

drug could also be misbranded. However, it does not appear that courts have found “that a product ‘is intended for use’

or ‘intended to affect’ within the meaning of the [FFDCA] absent manufacturer claims as to that product’s use.” SigmaTau Pharmaceuticals, Inc. v. Schwetz, 288 F.3d 141, 147 (May 2, 2002) (quoting Brown & Williamson Tobacco Corp.

v. FDA, 153 F.3d 155, 163 (4th Cir. 1998), aff’d, 529 U.S. 120 (2000)).

See 21 C.F.R. § 314.70.

21 U.S.C. § 321(m).

21 C.F.R. § 202.1(l)(2).

61 Fed. Reg. 52800 (Oct. 8, 1996). After the passage of FDAMA, the FDA issued a 1997 guidance on industrysupported scientific and continuing medical education activities that is still in effect. 62 Fed. Reg. 64073 (Dec. 3,

1997).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-3(a)). FDAMA also addressed information regarding off-label uses

of devices, which could be disseminated if the product was in commercial distribution and complied with specified

(continued...)

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

September 30, 2006.25 Other than the FDA’s 2009 guidance document, it does not appear that the

FDA currently has another statute, rule, or policy in effect that explicitly addresses the

dissemination of reprints or reference texts with regard to promoting an off-label use.26 This

section details the FDAMA provisions, which are similar, in parts, to those in the recent FDA

guidance and which provide a basis for understanding current discussions of the FDA’s January

2009 guidance.

As emphasized in a Federal Register notice post-FDAMA, § 401 created a safe harbor. As long as

information dissemination on off-label uses adhered to FDAMA, it was not to be construed as

evidence of a new intended use of a drug that differed from the intended use described in its

official labeling.27 Nor was it to be considered labeling, adulteration, or misbranding under the

FFDCA.28 To disseminate information, the manufacturer was required to submit to the Secretary a

copy of the information 60 days before distribution, including clinical trials and clinical

experience about the safety and effectiveness of the unapproved use, and to comply with the

requirements for filing a supplemental new drug application.29

Manufacturers were required to include a prominent statement showing the following, if

applicable: that the information concerned an unapproved use of a drug; that the disseminated

information was being paid for by the manufacturer; the names of any authors with financial ties

with the manufacturer; the official labeling for the drug; a statement that there were other

approved products or treatments for the use for which the information was being disseminated;

and the identification of all persons who funded any study about the off-label new use.30

Manufacturers were also required to include a bibliography of published articles about the

unapproved use from scientific or medical journals.31

If the Secretary determined, after providing notice and an opportunity for a meeting, that the offlabel use information failed to provide objective and balanced information, the Secretary could

have required the dissemination of additional information, along with a statement of the Secretary

about the safety and effectiveness of the drug’s unapproved use.32

(...continued)

classification and premarket approval regulations.

According to a letter from House Oversight and Government Reform Committee Chairman Henry Waxman to FDA

Commissioner Andrew von Eschenbach, “There was no effort to renew section 401 when Congress passed the FDA

Amendments Act of 2007.” Letter from Henry A. Waxman, Chairman, House Committee on Oversight and

Government Reform, to Andrew C. von Eschenbach, Commissioner, FDA, Nov. 30, 2007, at 5,

http://oversight.house.gov/documents/20071130102744.pdf. FDAMA § 401(f) required studies by the General

Accounting Office (now the Government Accountability Office, GAO) and the Institute of Medicine to examine,

among other things, the quality and usefulness of information disseminated and whether the § 401 termination date

should be extended. According to an individual at GAO who was not involved in the discussions at that time, neither

study was conducted. Telephone conversation with GAO employee, Mar. 12, 2008.

See id. (noting that 21 C.F.R. Part 99 and the FDAMA § 401 implementing regulations are now invalid); see also

Letter from Henry A. Waxman, Chairman, House Committee on Oversight and Government Reform, to Andrew C. von

Eschenbach, Commissioner, FDA, Jan. 22, 2008, at 2 n. 3, http://oversight.house.gov/documents/20080122141935.pdf.

63 Fed. Reg. 31143, 31144 (June 8, 1998).

Id. at 31144.

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(b)(4)-(5)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(b)(6)(A)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(b)(6)(B)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(c)).

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Manufacturers were allowed to disseminate information about an unapproved new use only if the

information was in the form of an unabridged reprint or copy of an article peer reviewed by

experts. The unabridged article was required to originate from a medical journal or a reference

publication, describe a scientifically sound clinical investigation, and not be false or misleading.

In addition, to disseminate off-label use information, manufacturers were required to prepare and

submit biannually to the Secretary a list of articles and reference publications about their drug’s

unapproved uses that were disseminated for the six-month period prior to the submission of the

list. Manufacturers were also required to submit lists that identified the categories of providers

that received that material for the same time period.

If the Secretary determined that the unapproved use may not have been effective or may have

presented a significant risk to the public health, the Secretary could have ordered corrective

action, including the cessation of dissemination of the information. In the event that the Secretary

required corrective action to be taken, manufacturers had to keep records regarding the

dissemination of off-label information that could be used in such situations. Manufacturers were

also responsible for reporting results of additional clinical research about the safety and

effectiveness of the unapproved use involved.

To disseminate off-label use information manufacturers were also required to submit a

supplemental new drug application to the Secretary, receive certification that they would file a

supplemental application based on completed or planned studies, or receive an exemption from

submitting such an application. A manufacturer could qualify for an exemption from the

requirement to submit a supplemental application in three situations.33 Exemptions could only

have been approved if the Secretary determined that the supplemental application would have

been economically prohibitive or if the Secretary determined that it would have been “unethical

to conduct the studies necessary for the supplemental application.”34 The Secretary could have

terminated such approval at any time and ordered the manufacturer to cease distributing the

information.

Legislative History

The legislative history provides some background for the policy reasons for including the

provision relating to off-label drug uses. Some of the issues raised prior to the enactment of the

now-defunct provision of FDAMA may still pose concerns today:

The conference agreement’s inclusion of [§ 401] is intended to provide that health care

practitioners can obtain important scientific information about the uses that are not included

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-3(b)-(d)). The manufacturer could either (1) certify that the studies

for a supplemental application were complete and that the supplemental application would be submitted within six

months after the initial dissemination of the information; or (2) submit a proposed protocol and schedule for studies for

the supplemental application that the Secretary has determined were adequate and reasonable, respectively, and certify

that the supplemental application would be submitted within 36 months after the initial dissemination of the

information; or (3) receive the Secretary’s approval for an application for an exemption from the requirement to submit

a supplemental application. Manufacturers were also required to submit periodic status reports. If the Secretary

determined that the studies could not be completed and submitted within 36 months, or the manufacturer had submitted

a written request for an extension and the Secretary determined that the manufacturer had diligently conducted the

studies, an extension of up to 24 months could have been provided.

P.L. 105-115, § 401(expired 21 U.S.C. § 360aaa-3(d)(2)).

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in the approved labeling of drugs, biological products, and devices. The conferees also wish

to encourage that these new uses be included on the product label. Therefore, the agreement

includes strong incentives to conduct the research needed and file a supplemental application

for such uses.35

The House Report on the earlier House version of the FDAMA, H.R. 1411, remarked on the

FDA’s jurisdiction and authority with regard to the dissemination of information by

manufacturers. The report noted that the agency “has a role to play with respect to assuring

balance and objectivity and to protecting the public health.”36

Representative Markey, on the other hand, took issue with the off-label provisions:

The drug bill contains a dangerous and precedent-setting provision regarding dissemination

of information. The “Off-label” provision could better be described as the “under the table”

provision, allowing companies to market a product for unsupported uses that could seriously

send thousands of consumers “off the cliff.” In putting profits over patient care, this bill

opens the door for aggressive promotion of unproven uses of drugs, while giving companies

three to five years to produce scientific evidence that these off-label uses are safe and

effective.... 37

The FDA’s January 2009 Guidance

The FDA’s guidance on good reprint practices was issued in the last few days of the Bush

Administration. It contains provisions similar to some of the FDAMA dissemination provisions

that expired in 2006, but also appears to expand the ability of the pharmaceutical industry to

disseminate such information.

The guidance differs in several ways from the expired FDAMA provisions. The guidance does

not include the following, which were present in FDAMA: (1) the requirement for a submission

of a supplemental new drug application or the Secretary’s approval of an application for an

exemption from this requirement;38 (2) the Secretary’s ability to require a manufacturer to

disseminate (a) additional scientifically sound information to provide objectivity and balance, and

(b) a statement from the Secretary on the safety and effectiveness of the unapproved use;39 (3) the

Secretary’s ability to order the manufacturer to cease dissemination of information in certain

situations, such as if the Secretary determined that the unapproved use may not be effective or

may present a significant risk to public health, or if the information did not comply with

FDAMA’s provisions;40 (4) provisions that required manufacturers to submit lists of the articles

and reference publications that they disseminated and to keep records in case the manufacturer

H.Rept. 105-399 (2007) (Conf. Rep.); see also H.Rept. 105-310 (Oct. 7, 1997) (“The principal policy considerations

that underlie this provision are the facilitation of greater access to timely and accurate information by health care

providers.”).

H.Rept. 105-310 (Oct. 7, 1997). The Senate version of FDAMA (S. 830) did not contain similar provisions regarding

dissemination of information on new uses but rather discussed “the danger that policies related to dissemination of

health economic information will become an avenue for off-label promotion of unsubstantiated clinical efficiency

claims.” S.Rept. 105-43 (July 1, 1997).

Id.

See Guidance, supra note 3; P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-3).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(c)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-4).

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was required to take corrective action;41 (5) the requirement that the manufacturer include, along

with the information being disseminated, “a statement that there are products or treatments that

have been approved or cleared for the use that is the subject of the information being

disseminated” and, if applicable, a statement “that the information is being distributed at the

expense of the manufacturer”;42 (6) the requirement that a copy of the information to be

disseminated and clinical trial information regarding the unapproved use be submitted to the

Secretary 60 days prior to dissemination;43 (7) the requirement that the article not have

unapproved uses of drugs or devices as its primary focus;44 and (8) a provision requiring that a

scientific or medical journal be a publication “that is generally recognized to be of national scope

and reputation.”45

However, the guidance also contains new potential safeguards that were not present in FDAMA,

such as (1) the recommendation that reprints of scientific articles not be distributed with

promotional materials, at promotional exhibit halls, or during promotional speaker events, in

addition to not being the topic of discussion during a sales visit by a sales representative to a

physician’s office; (2) the recommendation that a journal reprint be accompanied by a statement

disclosing “all significant risks or safety concerns known to the manufacturer concerning the

unapproved use that are not discussed in the journal article” and a disclosure of “the

manufacturer’s interest in the drug or medical device that is the subject of the journal reprint or

reference text”; (3) examples of what would constitute false or misleading information, such as a

reprint of an article that is characterized as definitive but “is inconsistent with the weight of

credible evidence”; and (4) examples of publications that would not meet the guidance’s

recommendations, such as reports of early clinical trials in healthy subjects.46

The guidance seemingly creates a safe harbor for dissemination of information on off-label uses

of FDA-approved drugs by stating that “if a manufacturer follows [its] recommendations ... the

FDA does not intend to consider the distribution of such medical and scientific information in

accordance with the recommendations in this guidance as establishing intent that the product be

used for an unapproved new use.”47 While some view the document as shielding a “controversial

promotional practice,” others believe the guidance would “probably restrict more aggressive

companies.”48 Additionally, the document’s issuance, along with a set of proposed rules and other

guidance documents, has been criticized by some who are concerned that the FDA may be

placing pharmaceutical industry priorities over public health protections for consumers.49

Questions have been raised regarding whether the FDA has the authority to issue this guidance

document.

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-2).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(b)(6)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa(b)(4)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-1((b)(4)).

P.L. 105-115, § 401 (expired 21 U.S.C. § 360aaa-5(5)(C)).

See Guidance, supra note 3.

Id.

Wilde Mathews and Johnson, supra note 11.

Letter from Henry A. Waxman, Chairman, House Committee on Oversight and Government Reform, to Andrew C.

von Eschenbach, Commissioner, FDA, Sept. 17, 2008, at 2, http://oversight.house.gov/documents/

20080917113245.pdf.

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Administrative Law Issues

FDA rules may be subject to legal challenges. This section addresses administrative law

principles that may come into play in the event that the FDA’s guidance is implemented or

enforced in a manner that would render it a binding rule that should have been promulgated under

the provisions of the Administrative Procedure Act (APA). Additionally, this section addresses the

question of whether the FDA had the authority to issue such a guidance document, due to the

expiration of the FDAMA provisions.

Rules and Guidance Documents

Agency rules have the force and effect of law and may be reviewed and invalidated by courts.50

Under notice-and-comment rulemaking procedures, agencies must publish notice of a proposed

rulemaking in the Federal Register, provide opportunity for the submission of comments by the

public, and publish a final rule and a general statement of basis and purpose in the Federal

not have to undergo notice-and-comment procedures. They do not have the force and effect of

law; they are a type of general statement of policy.52 General statements of policy are agency

statements that “advise the public prospectively of the manner in which the agency proposes to

exercise a discretionary power.”53 General statements of policy do not “impose any rights and

obligations,”54 nor do they “establish a ‘binding norm’” because they do not represent the final

determination regarding the issues they address.55

Congress has passed requirements specific to FDA guidance documents, which note that such

documents “shall not create or confer any rights for or on any person, although they present the

views of the Secretary on matters under the jurisdiction of the Food and Drug Administration.”56

Thus, while the FDA guidance on reprint practices indicates the agency’s thoughts on the topic

and potentially how the agency itself would use, or rather limit its use of, its enforcement

powers—such as criminal and civil penalties, injunctions, and seizures—with regard to the

practices outlined in the guidance, the document is not legally binding on courts or persons

outside the agency.57

A guidance document can become binding on an agency in practice, however. One academic has

commented that “[i]n some circumstances, if the language of the document is such that private

parties can rely on it as a norm or safe harbor by which to shape their actions, it can be binding as

5 U.S.C. §§ 551(4), 701-06; Appalachian Power Co. v. EPA, 208 F.3d 1015, 1020 (D.C. Cir. 2000).

5 U.S.C. § 553(c), (d).

JEFFREY S. LUBBERS, A GUIDE TO FEDERAL AGENCY RULEMAKING 94 (4th ed. 2006). Executive Order 13422 sets forth

a definition of a guidance document. Executive Order 13422, Further Amendment to Executive Order 12866 on

Regulatory Planning and Review, Jan. 18, 2007, http://www.whitehouse.gov/news/releases/2007/01/20070118.html.

Tom C. Clark, Attorney General, Attorney General’s Manual on the Administrative Procedure Act, at 30 n.3 (1947),

http://www.law.fsu.edu/library/admin/1947iii.html; see, e.g., Chamber of Commerce v. United States Department of

Labor, 174 F.3d 206, 212 (D.C. Cir. 1999).

Community Nutrition Institute v. Young, 818 F.2d 943, 946 (D.C. Cir. 1987) (internal quotations omitted).

Pacific Gas & Electric Co. v. Federal Power Commission, 506 F.2d 33 (D.C. Cir. 1974).

21 U.S.C. § 371(h). The provisions on guidance documents were added in 1997 by FDAMA § 405.

Guidance, supra note 3.

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a practical matter.”58If a policy statement is implemented in a manner that is binding on the

agency and outside parties, it will be regarded as a rule and will be deemed invalid for failing to

comply with APA notice and comment procedures.59 APA procedural requirements do not apply

to “interpretive rules, general statements of policy, or rules of agency organization, procedure, or

practice,” unless such documents are, in fact, binding, substantive rules.60

Is the Guidance a Substantive Rule Subject to a Notice-andComment Rulemaking?

This dynamic raises the question as to whether the FDA’s guidance will be implemented in a

manner that will in fact render it a rule that must have been promulgated under the notice-andcomment procedures in the APA. Since the guidance document was recently issued, it is not clear

how the agency and the pharmaceutical industry will use the document. Additionally, the FDA

under the Obama Administration may approach this issue differently than the Bush

Administration.61

If the FDA treats the guidance document as both prospective and voluntary, and as a policy that

preserves the agency’s discretion, then the document will not likely be considered a substantive

rulemaking document that needs to follow APA notice-and-comment procedures nor be

considered to be in violation of the APA. If the FDA uses the guidance document in a manner that

constitutes the agency’s implementation of a substantive rule, then a reviewing court could

determine that the FDA would be in violation of the APA requirements for notice-and-comment

rulemaking. A reviewing court would examine whether the document has a binding effect,62

whether the agency retains its ability to exercise discretion,63 whether the document uses

voluntary or mandatory language,64 and whether the FDA characterizes the document as

guidance,65 in order to determine if the guidance document is in fact a substantive rule.

Professor Robert A. Anthony (quoted in LUBBERS, supra note 52, at 100); see also Robert A. Anthony, Interpretive

Rules, Policy Statements, Guidances, Manuals, and the Like—Should Agencies Use Them to Bind the Public?, 41 Duke

L. J. 1463 (1992).

Bellarno Int’l v. Food and Drug Administration, 678 F. Supp. 410 (E.D.N.Y. 1988).

5 U.S.C. § 553(b). Some agencies have been criticized for using guidance documents to “issue or amend [their] real

rules, i.e., [their] interpretative rules and policy statements, quickly and inexpensively without following any statutorily

prescribed procedures.” Appalachian Power Co. v. EPA, 208 F.3d 1015, 1020 (D.C. Cir. 2000) (quoting Richard J.

Pierce, Jr., Seven Ways to Deossify Agency Rulemaking, 47 ADMIN. L. REV. 59, 85 (1995)).

Neither of the two Obama Administration memoranda issued to the heads of executive departments and agencies

(regarding steps to be taken with regard to various proposed and final regulations issued in the last few months of the

Bush Administration) applies to this guidance document because guidance documents are not addressed in such

memoranda. Memorandum from Rahm Emanuel, White House Chief of Staff and Assistant to the President, White

House (Jan. 20, 2009), http://edocket.access.gpo.gov/2009/pdf/E9-1639.pdf; Memorandum from Peter R. Orszag,

Director, Office of Management and Budget (Jan. 21, 2009), http://www.whitehouse.gov/omb/assets/

agencyinformation_memoranda_2009_pdf/m09-08.pdf.

“If an agency acts as if a document issued at headquarters is controlling in the field, if it treats the document in the

same manner as it treats a legislative rule, if it bases enforcement actions on the policies or interpretations formulated in

the document, if it leads private parties or State permitting authorities to believe that it will declare permits invalid

unless they comply with the terms of the document, then the agency’s document is for all practical purposes ‘binding.’”

Appalachian Power Co. v. EPA, 208 F.3d 1015, 1021 (D.C. Cir. 2000).

American Bus Ass’n v. United States, 627 F.2d 525, 529 (D.C. Cir. 1980); see also Chamber of Commerce v. United

States Department of Labor, 174 F.3d 206, 212 (D.C. Cir. 1999).

Courts have held that the language an agency uses can determine whether a document is a general statement of policy

(continued...)

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Additionally, some have argued that a guidance document can become “binding as a practical

matter” in some cases “if the language of the document is such that private parties can rely on it

as a norm or safe harbor by which to shape their actions.”66 It is not known how the

pharmaceutical industry would rely on the guidance document, although the document itself is

similar in many respects to the FDAMA provisions that Congress did not renew in 2006.

Presumably, the pharmaceutical industry could have relied on the FDAMA provisions and the

FDA’s implementing regulations while they were in effect, in order for the manufacturer’s

distribution of reprints regarding off-label uses not to be used in an enforcement case as evidence

of the manufacturer’s intent that a drug be used for an unapproved, off-label use.67 Therefore, it

seems that pharmaceutical manufacturers could attempt to use the FDA guidance as a safe harbor

when distributing a peer-reviewed article.

Does the FDA Have the Authority to Issue the Guidance?

Additionally, the question arises as to whether the FDA has the authority to issue such guidance

because Congress had given the agency explicit authority on this topic in FDAMA but then did

not renew the provisions granting the agency that authority. In a letter to the FDA Commissioner,

Representative Waxman described the FDA’s issuance of the guidelines, in draft form, as “an

effort by FDA to displace Congress and establish by administrative fiat a new system for use of

journal articles that lacks the safeguards set by Congress.”68 A reviewing court would examine the

FFDCA, “and the ever-evolving statutory scheme, recognizing that the [FFDCA]’s meaning may

be affected by other Acts, particularly where Congress has spoken subsequently and more

specifically to the topic at hand.”69

(...continued)

or a substantive rule: While the agency’s characterization of an official statement as binding or nonbinding has been

given some weight, of far greater importance is the language used in the statement itself. We have, for example, given

decisive weight to the agency’s choice between the words “may” and “will.” In holding that a declaration of the

Interstate Commerce Commission was not a general statement of policy, we relied upon the fact that the

pronouncement at issue declared that “the Commission will” make certain demands of applicants for particular

certificates; while in holding that a pronouncement of the Federal Savings and Loan Insurance Corporation was nothing

more than a general statement of policy, we relied upon the use of the word “may” in its description of the agency’s

intended future course.Brock v. Cathedral Bluffs Shale Oil Co., 796 F.2d 533, 537-38 (D.C. Cir. 1986) (internal

citations omitted); see also Community Nutrition Institute v. Young, 818 F.2d 943, 947 (D.C. Cir. 1986).

In Professionals and Patients for Customized Care v. Shalala, the court noted that the FDA’s consistent

classification of a document as a policy statement was one factor “in favor of a holding that [a compliance policy guide

was] not a substantive rule.” 56 F.3d 592, 596 (5th Cir. 1995).

Professor Robert A. Anthony (quoted in LUBBERS, supra note 52, at 100); see also Robert A. Anthony, Interpretive

Rules, Policy Statements, Guidances, Manuals, and the Like—Should Agencies Use Them to Bind the Public?, 41 Duke

L. J. 1463 (1992).

See Guidance, supra note 3. According to House Oversight and Government Reform Committee Chairman Henry

Waxman, “[d]uring the period between enactment in 1997 and 2006, a number of abuses involving journal articles

occurred, including the abuses involving anti-depressants, Vioxx, Celebrex, and Neurontin described in this document.”

Letter from Henry A. Waxman, Chairman, House Committee on Oversight and Government Reform, to Andrew C. von

Eschenbach, Commissioner, FDA, Nov. 30, 2007, at 5, http://oversight.house.gov/documents/20071130102744.pdf.

Letter from Henry A. Waxman, Chairman, House Committee on Oversight and Government Reform, to Andrew C.

von Eschenbach, Commissioner, FDA, Nov. 30, 2007, at 5, http://oversight.house.gov/documents/

20071130102744.pdf.

Ass’n of American Physicians Surgeons, Inc. v. United States, 226 F. Supp. 2d 204, 212 (D.D.C. 2002) (quoting

FDA v. Brown & Williamson Tobacco Corp., 529 U.S. 120, 133 (2000)) (internal quotations omitted).

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The FDA could assert that its general statutes and regulations grant it such authority.70 FFDCA §

701(h)(5) required the FDA to issue regulations on the agency’s policies for developing, issuing,

and using guidance documents.71 FDA regulations on good guidance practices define a “guidance

document” to include “documents that relate to: The ... labeling [and] promotion ... of regulated

products ... and inspection and enforcement policies.”72 The FDA’s guidance on reprint practices

would appear to fall within the definition of a guidance document, as it relates to labeling and

promotion of unapproved new uses of FDA-approved drugs and medical devices. The FDA can

also assert that it has attempted to address dissemination of information on off-label uses even

prior to FDAMA.73 For example, in 1992, the FDA issued a notice asking for comment on a draft

policy statement regarding “the categories of educational activities that may continue to be

funded by industry and yet avoid regulation as advertising or promotional labeling.”74 It noted

that “[t]he companies’ programs and materials are subject to the labeling and advertising

provisions of the act.”75 Thus, based on these statutes and regulations, it would appear that the

FDA is acting on a legally tenable basis in issuing the guidance on the reprint practices.

Since the FDA’s guidance document does not have the force of law, to the extent that it is

challenged, it would not receive the same degree of deference as a substantive rule promulgated

under the APA notice and comment procedures.76 To the extent that the guidance document

receives deference by a reviewing court, that deference would be of the type elucidated in

Skidmore v. Swift & Co.:

[T]he rulings, interpretations and opinions of [the agency], while not controlling upon the

courts by reason of their authority, do constitute a body of experience and informed

judgment to which courts and litigants may properly resort for guidance. The weight of such

a judgment in a particular case will depend upon the thoroughness evident in its

consideration, the validity of its reasoning, its consistency with earlier and later

pronouncements, and all those factors which give it power to persuade, if lacking power to

control.77

FFDCA § 701(h) states that “[t]he Secretary shall develop guidance documents with public participation,” and

provides that “[f]or guidance documents that set forth initial interpretations of a statute or regulation, changes in

interpretation or policy that are of more than a minor nature, complex scientific issues, or highly controversial issues,

the Secretary shall ensure public participation prior to implementation of guidance documents.” 21 U.S.C. §§

371(h)(1)(A) and (C).

21 U.S.C. § 371(h)(5).

21 C.F.R. § 10.115(b)(2).

The FDA’s previous assertion of jurisdiction in this area could be contrasted with the agency’s “express[]

disavow[al]” of jurisdiction to regulate tobacco products, which the Supreme Court documented in FDA v. Brown &

Williamson Tobacco Corp. In that case, the FDA shifted its long-held position with regard to whether it had authority

to regulate tobacco. The Court held that “the FDA’s assertion of jurisdiction is impermissible” in light of congressional

intent to the contrary, as expressed in “the FDCA’s overall regulatory scheme and in the tobacco-specific legislation

that it has enacted subsequent to the FDCA.” 529 U.S. 120, 125-26 (2000). Given these factors, the sunset of FDAMA

does not necessarily indicate that Congress meant to keep the FDA from acting on its own authority.

FDA, Draft Policy Statement on Industry-Supported Scientific and Educational Activities, 57 Fed. Reg. 56412 (Nov.

27, 1992).

Id.

See Skidmore v. Swift & Co., 323 U.S. 134, 140 (1944).

Id.; see also Christensen v. Harris County, 529 U.S. 576, 587 (2000); Ohio Pub. Employees Retirement System v.

Betts, 492 U.S. 158, 171 (1989) (“no deference is due to agency interpretations at odds with the plain language of the

statute itself”).

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In other words, courts will often give weight to an agency’s interpretations, due to the agency’s

“specialized experience” in the administration of its given functions.78 Such agency documents

are entitled to a “respect proportional to [their] ‘power to persuade.’”79 In the guidance document,

the FDA appears to be loosening the standards passed by Congress on off-label marketing,

without regard to the sunset of the FDAMA provisions on the dissemination of information

regarding off-label uses in 2006 and subsequent congressional silence.80 Therefore, a court may

give less deference to the agency or find the guidance document unpersuasive due to its lack of

consistency with earlier agency positions, in particular, those mandated by Congress.

In a case addressing an agency’s jurisdiction, when a specific statutory provision prohibited the

Federal Communications Commission (FCC) from having jurisdiction over certain intrastate

communication services, but the agency attempted to exercise its jurisdiction in that area

regardless, the Supreme Court stated the following:

[A]n agency literally has no power to act ... unless and until Congress confers power upon

it.... Thus, we simply cannot accept an argument that the FCC may nevertheless take action

which it thinks will best effectuate a federal policy. An agency may not confer power upon

itself. To permit an agency to expand its power in the face of a congressional limitation on its

jurisdiction would be to grant to the agency power to override Congress.81

Although Congress did not enact a specific statute prohibiting the FDA from addressing reprint

practices, it is conceivable that some might assert the agency’s action—in light of Congress’s

decision to legislate the sunset of the off-label provisions—could be viewed as an attempt by the

FDA to alter federal policy in the area.82 Alternately, the FDA’s statutes appear to grant the

agency authority to issue guidance documents relating to promotion of FDA-regulated products.

The congressional silence in this area since the sunset of FDAMA stands in contrast to other cases

where Congress has considered and rejected bills on the subject.83

First Amendment Challenges

Assuming that the FDA has the authority to issue the guidance, these provisions may face a First

Amendment challenge. FDAMA § 401 and the earlier 1996 FDA guidance documents (both of

which addressed permissible methods for the dissemination of information about “off-label” uses

by drug manufacturers) have been challenged on First Amendment grounds. The U.S. District

Court for the District of Columbia initially found that these provisions violated the First

United States v. Mead Corp., 533 U.S. 218, 234 (2001).

Id. at 235 (quoting Skidmore v. Swift & Co., 323 U.S. 134, 140 (1944)).

See e.g. Whitman v. Am. Trucking Ass’n, Inc., 531 U.S. 457 (2001); see, e.g., Sullivan v. Zebley, 493 U.S. 521

(1990) (finding regulations “are simply inconsistent with the statutory standard”); Dole v. Steelworkers, 494 U.S. 26

(1990) (foreclosing deference to OMB’s interpretation of the Paperwork Reduction Act because the Court held that

there was clear congressional intent to the contrary).

La. Pub. Serv. Comm’n v. FCC, 476 U.S. 355, 374-75 (1986).

See Ass’n of American Physicians Surgeons, Inc. v. United States, 226 F. Supp. 2d 204 (D.D.C. 2002) (finding that

the FDA’s pediatric rule exceeded the authority delegated to the agency by Congress because the specific statutory

provisions in the FFDCA did not provide a “sound basis” for the rule and because it was incompatible with the Best

Pharmaceuticals for Children Act (BPCA), although Congress did not explicitly reject the pediatric rule in enacting

BPCA).

See, e.g., FDA v. Brown & Williamson Tobacco Corp., 529 U.S. 120, 155, 159-60 (2000).

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Amendment and issued an injunction.84 However, subsequent developments at the Court of

Appeals level caused the injunction to be vacated, leaving the constitutional question open.85 This

section will briefly describe these cases.

The Washington Legal Foundation (WLF), a nonprofit group that advocates against excessive

government regulation, challenged earlier FDA guidance documents (issued in 1996) dealing with

the distribution of enduring materials86 by drug manufacturers. In particular, the WLF argued that

the FDA was impermissibly restricting constitutionally protected speech.87 The district court in

WLF v. Friedman (WLF I) determined that the FDA was restricting protected speech, but that the

speech was entitled to a lower degree of constitutional protection because it was commercial in

nature (rather than wholly scientific or academic, as WLF argued).88 In order for a restriction on

commercial speech to be constitutional, the restriction must satisfy a four-part test.89

The first question addressed in the four-part test is whether the speech covered by the restriction

is false, misleading, or concerns an illegal activity.90 The First Amendment does not protect

commercial speech concerning unlawful activities or false or deceptive advertising.91 The district

court in WLF I determined that the speech addressed by the FDA guidance did not concern an

illegal activity, because the speech being distributed by the drug manufacturers “addresse[d]

using FDA-approved drugs to treat conditions and in treatment regimens other than those set forth

in the label approved by the FDA,” an activity that is not unlawful.92 A closer question for the

court was the whether the speech could be deemed false or misleading. Here, the court looked at

whether the information being distributed could be characterized as “inherently misleading.”93 In

making its determination, the court looked at the controls available to the FDA concerning the

information that may be distributed by the manufacturers.94 The court found that these controls

Washington Legal Foundation v. Friedman, 13 F.Supp. 2d 51, 54 (D.D.C. 1998) (“WLF I”).

It should be noted that the cases discussed in this section analyze the constitutionality of regulatory guidance and

statutory provisions that are no longer in force. These cases, however, may be referenced by a court that is evaluating

the constitutionality of current guidance due to the similarities between the previous scheme and the recently issued

guidance documents.

Enduring materials are reprints of medical textbooks and peer-reviewed journal articles. WLF I, 13 F.Supp. 2d at 51

(internal citations omitted).

WLF I, 13 F.Supp. 2d at 54.

Id. at 62-65.

Central Hudson Gas and Electric Corp. v. Public Service Comm’n of New York, 447 U.S. 557 (1980).

In re R.M.J., 455 U.S. 191, 200 (1982) (“False, deceptive or misleading advertising remains subject to restraint.”).

Pittsburgh Press Co. v. Pittsburgh Comm’n on Human Relations, 413 U.S. 376, 37 L. Ed. 2d 669, 93 S. Ct. 2553

(1973).

WLF I, 13 F.Supp. 2d at 66. The FDA argued that the speech at issue in this case could not survive the first prong of

the constitutional test, because when a manufacturer promotes a drug for an unapproved use the manufacturer may be

engaged in misbranding, which is illegal. The court rejected this argument. The court found that the proper test was not

whether the speech at issue violated a law or regulation, but whether the speech promoted conduct that is illegal.

Because the speech in this case promotes conduct that is legal (that is the “off-label” prescription of drugs), the speech

does not promote illegal activities. Id. However, if Congress were to ban the prescription of drugs for off-label uses, the

free speech analysis of this question would change, as speech regarding off-label uses of FDA-approved drugs would

then concern an illegal activity.

WLF I, 13 F.Supp. 2d at 67 (“In order to end the Central Hudson analysis on the first prong, the speech must be

‘inherently misleading,’ which is defined in Central Hudson as ‘more likely to deceive the public than to inform it.’

Central Hudson, 447 U.S. at 563.”)

WLF I, 13 F.Supp. 2d at 67.

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circumscribed the possibility that untruthful or misleading information could be disseminated by

manufacturers. As a result, the court did not consider the speech to be inherently misleading. The

speech at issue, therefore, is entitled to some degree of First Amendment protection.

In order to determine whether the FDA’s policies were a constitutionally permissible restriction

on commercial speech, the court proceeded to the next three steps of the constitutional analysis:

(1) whether the government has a substantial interest in imposing the restriction on speech; (2)

whether the restriction at issue directly advances that interest; and (3) whether the restriction at

issue is not more extensive than necessary to achieve that interest.

The court found that the government does have a substantial interest in encouraging drug

manufacturers to get off-label treatments on-label, as many uses for drugs that have been

approved in other treatment contexts would otherwise evade the FDA approval process (a process

that Congress has declared all uses for drugs should endure).95 The court also found that

restricting marketing options for off-label uses of approved drugs advances this interest, because

it is “one of the few mechanisms available to the FDA to compel” manufacturers to seek FDA

approval for off-label uses (considering that the conventional mechanism of preventing the drug

from being introduced into interstate commerce is unavailable because FDA-approved drugs may

be introduced into interstate commerce, regardless of whether they will be prescribed for an offlabel use or an FDA-approved use).96

However, the court found that the guidance documents at issue in this case were nonetheless

unconstitutional, because they were, in the court’s estimation, more extensive than necessary to

achieve the stated interest.97 Though, under a commercial speech analysis, the government need

not choose the least restrictive method for achieving its goal, an effort must be made to create a

reasonable fit between the method chosen and the ends sought.98 If a commercial speech

restriction burdens substantially more speech than necessary, courts will not allow the restriction

to take effect.99 The district court, finding that the FDA guidance burdened substantially more

speech than necessary, cited at least one alternative method that the government could have used

to achieve its objectives, which placed a significantly smaller burden on protected speech.100 For

example, the court hypothesized that requiring complete and unambiguous disclosure by

manufacturers who would disseminate the information at issue would be equally effective in

achieving the government’s goal and would place a lesser burden on speech.101

As a result, the court held that while the government may restrict drug manufacturer promotion of

off-label uses, the restrictions in the guidance documents were too extensive to withstand

constitutional scrutiny. The district court issued an injunction barring the FDA from prohibiting,

restricting, or sanctioning drug manufacturers “for disseminating or redistributing to physicians or

other medical professionals any article concerning prescription drugs or medical devices

previously published in a bona fide peer-reviewed professional journal, regardless of whether

such article includes a significant or exclusive focus on uses of drugs or medical devices other

Id. at 70-71.

Id. at 72.

Id.

Board of Trustees of the State University of New York v. Fox, 492 U.S. 469, 478 (1989).

United States v. Edge Broadcasting Co., 509 U.S. 418, 430 (1993).

100

WLF I, 13 F.Supp. 2d at 73.

101

Id.

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than those approved by FDA and regardless of whether such article reports the original study on

which FDA approval of the drug or device in question was based.”102

Following the issuance of this injunction, which applied to the guidance documents of 1996,

FDAMA took effect in 1997 and superseded the guidance documents. The district court amended

its injunction to clarify that the injunction applied with equal force to FDAMA. Though some

aspects of FDAMA were different from the previous guidance documents, the court ultimately

determined that the underlying policies in FDAMA largely duplicated those of the guidance

documents and were unconstitutional for similar reasons.103 The FDA appealed.

The U.S. Court of Appeals for the District of Columbia described the parties’ briefs in this case as

“confusing.”104 The fundamental disconnect in the opposing parties’ arguments became clear only

at oral argument. WLF, in briefings and at oral argument, challenged the FDA’s guidance

documents under the theory that the FDA was banning independently the manufacturer

dissemination of enduring materials on off-label uses and that proof of such dissemination would

alone justify enforcement action. The FDA, however, asserted at oral argument that the FDAMA

provided a “safe harbor” for the dissemination of such information, and that “the agency would

draw no independent prosecutorial authority from the FDAMA to buttress any enforcement

proceeding.”105 The FDA, though reserving the right to use such promotional conduct as evidence

in a misbranding or “intended use” enforcement action, claimed no independent authority to

regulate speech through the FDAMA.

Because both parties, at that point, agreed that there was no constitutional controversy, the court

of appeals declined to rule on the constitutionality of the provisions at issue. Furthermore, since

no controversy over the FDA’s newly clarified interpretation existed, the court vacated the

injunction that declared FDAMA to be unconstitutional and dismissed the FDA’s appeal. In

disposing of the case in such a manner, the court noted that it was not criticizing or overruling the

reasoning of the district court on the First Amendment issue as it had been presented to the

district court. The appeals court also made clear that a manufacturer may still bring suit in order

to argue that the FDA’s use of a manufacturer’s promotion of off-label uses as evidence in an

enforcement action violates the First Amendment.106

In the guidance document released earlier this year, the FDA appears to create a “safe harbor”

similar to that which was previously in place under FDAMA.107 The FDA does not claim to draw

independent enforcement authority from violations of the guidance. Instead, the agency said that

it does not intend to consider information distributed in compliance with the guidance documents

as “establishing intent that the product be used for an unapproved new use.”108 The FDA reserves

the right to consider information that is distributed outside the parameters of the guidance as

evidence in establishing such intent, however. In light of this, a manufacturer (or any other

plaintiff with standing to sue) may challenge under the First Amendment the FDA’s use of off102

Id. at 74.

See Washington Legal Foundation v. Friedman, 36 F.Supp. 2d 16 (D.D.C. 1999)(“WLF II”); Washington Legal

Foundation v. Henney, 56 F.Supp. 2d 81 (D.D.C. 1999)(“WLF III”).

104

Washington Legal Foundation v. Henney, 202 F.3d 331, 335 (D.C. Cir. 2000).

105

Id. at 336.

103

106

Id. at 336-37, n. 6, n. 7.

See Guidance, supra note 3.

108

Id.

107

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label promotion as evidence in other enforcement actions.109 If the speech is used as evidence to

establish an element of a violation which itself is a restriction on lawful commercial speech, that

violation may also be challenged on First Amendment grounds.

False Claims Act Issues

The False Claims Act

The FDA’s new guidance regarding the promotion of off-label drug uses may also raise issues

under the False Claims Act. Under the FCA, any person who “knowingly presents, or causes to be

presented, ... a false or fraudulent claim for payment or approval” to the United States

government may be subject to civil penalties.110 Penalties under the FCA include treble damages,

plus an additional penalty of $5,500 to $11,000 for each false claim filed.

Civil actions may be brought in federal district court under the False Claims Act by the Attorney

General or by a whistleblower, for the person and for the U.S. Government, in what is termed a

qui tam action. The ability to initiate a qui tam action has been viewed as a powerful weapon

against fraud, in that it may be initiated by a private party who may have direct and independent

knowledge of any wrongdoing.111 The popularity of qui tam actions brought under the FCA may

be attributed partially to the fact that successful whistleblowers can receive between 15% and

30% of the monetary proceeds of the action or settlement that are recovered by the

government.112

False Claims Act Cases Involving Off-Label Promotion

In the context of manufacturer promotion of off-label uses of drugs, several qui tam actions have

been brought in recent years using the FCA. One of the largest settlements resulted from a case

109

See WLF IV, 202 F.3d at 336-37, n. 6. Such a challenge may be difficult to maintain in light of Wisconsin v.

Mitchell, 508 U.S. 476 (1993). In that case, the Supreme Court held that “the First Amendment ... does not prohibit the

evidentiary use of speech to establish the elements of a crime or to prove motive or intent.” Id. at 489.

110

31 U.S.C. § 3729. For additional discussion of the FCA, see CRS Report RL30463, Constitutional Aspects of Qui

Tam Actions: Background and Analysis of Issues in Vermont Agency of Natural Resources v. United States ex rel.

Stevens, by (name redacted) and CRS Report RS22743,

Health Care Fraud and Abuse Laws Covering Medicare and

Medicaid: An Overview, by Jennifer Staman. The government may be able to bring an action for a false claim under

several statutes other than the False Claims Act. See, e.g., 18 U.S.C. § 1347.

111

Health Law, 50 (Barry Furrow 2d ed. 2000).

112

Prosecution under the FCA may also be more attractive for the government. It has been pointed out that the terms of the

act are relatively simple and straightforward, and can be applied generally to healthcare providers. See Dayna Bowen

Matthew, An Economic Model to Analyze the Impact of False Claims Act Cases on Access to Healthcare for the Elderly,

Disabled, Rural and Inner-City Poor, 27 AM. J. L. AND MED. 439 (2001). Furthermore, because the FCA is a civil statute,

there is an easier burden of proof to meet (preponderance of the evidence) than there would be in a criminal statute (beyond

a reasonable doubt). Id.

However, the government has also achieved successful results outside of the FCA by alleging misbranding alone. In

December 2005, Eli Lilly and Company plead guilty to criminal misbranding of the osteoporosis drug Evista under the

FFDCA and paid fines and equitable disgorgement totaling $36 million. Eli Lilly allegedly “promoted Evista as

effective for reducing the risk of breast cancer, even after Lilly’s proposed labeling for this use was specifically

rejected by the FDA.” DOJ, Press Release, Eli Lilly and Company to Pay U.S. $36 Million Relating to Off-Label

Promotion, Dec. 21, 2005, http://www.usdoj.gov/opa/pr/2005/December/05_civ_685.html.

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

brought by a whistleblower named Dr. David Franklin against his former employer, WarnerLambert Co., a pharmaceutical company.113 In that case, Franklin alleged that Warner-Lambert

promoted off-label uses of the drug Neurontin, and that such promotion “caused the submission

of false claims to the Veterans Administration and to the federal government for Medicaid

reimbursement.”114 The court in that case explained the interaction of off-label prescribing and

Medicaid reimbursement:

Reimbursement under Medicaid is, in most circumstances, available only for “covered

outpatient drugs.” 42 U.S.C. § 1396b(i)(10). Covered outpatient drugs do not include drugs

that are “used for a medical indication which is not a medically accepted indication.” Id. §

1396r-8(k)(3). A medically accepted indication, in turn, includes a use “which is approved

under the [FFDCA]” or which is included in a specified drug compendia. Id. § 1396r-8(k)(6).

See also id. § 1396r-8(g)(1)(B)(i) (identifying compendia to be consulted). Thus, unless a

particular off-label use for a drug is included in one of the identified drug compendia, a

prescription for the off-label use of that drug is not eligible for reimbursement under

Medicaid.115

Neither Neurontin, or Accupril, another drug for which Warner-Lambert’s marketing practices

were at issue, had off-label uses that were present in the indicated compendia.116 Neurontin had

only been approved by the FDA for use in conjunction with other drugs “to control seizures in

people with epilepsy.”117 However, Dr. Franklin alleged that Warner-Lambert sales

representatives called “medical liaisons” were trained to discuss reports of Neurontin’s

effectiveness as a mono-therapy to treat epilepsy, meaning the use of Neurontin without the other

drugs with which its safety and effectiveness had been presented to FDA.118 The medical liaisons

also allegedly reported that the use of the drug for bipolar disease, pain syndromes, and attention

deficit disorders was effective according to clinical trials and other reports, though no such data

existed.119

The case settled and did not go to trial. Pfizer, which merged with Warner-Lambert, paid criminal

monetary penalties for its violations of the FFDCA and civil monetary penalties for its violations

of the FCA totaling $430 million. Pfizer pled guilty to two felony violations of the FFDCA—one

for misbranding due to a failure to give adequate directions for use120 and one for introducing an

113

United States ex rel. Franklin v. Warner-Lambert Co., 147 F. Supp. 2d 39 (D. Mass. 2001).

Id. at 43.

115

Id. at 44-45. The court also noted that “[p]ayment for certain drugs that are not otherwise covered may be allowed

where the drugs have been determined to be ‘essential to the health of beneficiaries.’ 42 U.S.C. § 1396r-8(a)(3).” For a

drug to be covered under that exception, it must also “ha[ve] been given a rating of 1-A by the Food and Drug

Administration; and ... the physician has obtained approval for use of the drug in advance of its dispensing in

accordance with a prior authorization program.” Id. at 45. It does not seem that most cases potentially brought under

the FCA would meet these requirements.

116

Id.; DOJ, Press Release, Warner-Lambert to Pay $430 Million to Resolve Criminal & Civil Health Care Liability

Relating to Off-Label Promotion, May 13, 2004, http://www.usdoj.gov/opa/pr/2004/May/04_civ_322.htm; FDA, Drug

Maker to Pay $430 Million in Fines, Civil Damages, FDA Consumer Magazine, (July - Aug. 2004)

http://www.fda.gov/fdac/features/2004/404_wl.html.

117

FDA, supra note 116.

118

See Franklin, 147 F. Supp. 2d at 48.

119

Id. at 48-49.

120

FDA, Drug Maker to Pay $430 Million in Fines, Civil Damages, FDA Consumer Magazine, (July - Aug. 2004),

http://www.fda.gov/fdac/features/2004/404_wl.html; 21 U.S.C. § 331(a).

114

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unapproved new drug in interstate commerce121—for which it agreed to pay a $240 million

criminal fine.122 Additionally, the company paid the United States government $83.6 million, plus

interest, for its civil liability under the FCA for Medicaid reimbursement claims;123 $68.4 million,

plus interest, to the states and the District of Columbia for state Medicaid losses; and $38 million,

plus interest, “for harm caused to consumers and to fund a remediation program to address the

effects of Warner-Lambert’s improper marketing scheme.”124 Finally, Pfizer agreed to a corporate

integrity agreement that addresses the “training and supervising [of] its marketing and sales staff,

and ensures that any future off-label marketing conduct is detected and corrected on a timely

basis.”125

The Warner-Lambert court’s reasoning is similar to that presented in other FCA suits related to

marketing of off-label drug uses for which Medicaid, Medicare, or a governmental entity

reimbursed the claims that were false because of the off-label use. For example, in a separate

FCA qui tam case, the U.S. government alleged that the pharmaceutical manufacturer Cell

Therapeutics, Inc., “made false and misleading statements to treating doctors to the effect that [an

acute promyelocytic leukemia drug] Trisenox was medically accepted for the off-label uses being

promoted, and therefore eligible for Medicare reimbursement.”126 The whistleblower in this case

was a former sales representative who alleged that the manufacturer unlawfully marketed

Trisenox for diseases such as chronic myeloid leukemia to physicians who had rarely, if ever,

treated patients with the disease (acute promyelocytic leukemia) for which use of the drug was

FDA-approved.127

The manufacturer allegedly caused false and misleading statements about the drug’s indications

to appear in a medical bulletin that doctors use to find answers regarding Medicare

reimbursement; the manufacturer’s sales representatives then distributed thousands of copies of

the bulletin to doctors to “mislead physicians into mistakenly believing that off-label Trisenox

prescriptions were medically accepted and reimbursable.”128 The government alleged that the

false statements resulted in Trisenox being misbranded and that the company had shipped it as an

unapproved new drug in interstate commerce, both violations of the FFDCA.129 The Department

121

21 U.S.C. § 331(d).

DOJ, Plea Agreement, Re: Warner-Lambert Company LLC, http://fl1.findlaw.com/

news.findlaw.com/hdocs/docs/pfizer/uswl51304plea.pdf. The plea agreement included an estimate that the company

gained $150 million.

123

DOJ, Settlement Agreement and Release, United States ex rel. Franklin v. Warner-Lambert Co.,

http://www.usdoj.gov/civil/foia/elecread/2004/Pfizer%20Inc.%202004.pdf.

124

DOJ, Press Release, Warner-Lambert to Pay $430 Million to Resolve Criminal & Civil Health Care Liability

Relating to Off-Label Promotion, May 13, 2004, http://www.usdoj.gov/opa/pr/2004/May/04_civ_322.htm.

125

Id.

126

United States ex rel. James Marchese v. Cell Therapeutics, Inc., Civil Action No. 06-168-MJP (W.D. Wash

complaint in intervention filed Apr. 16, 2007), at 2. “Trisenox was not approved by the FDA for any indication other

than” the treatment of acute promyelocytic leukemia. Id. at 10. Medicare Part B provides for only very limited

coverage of drugs, but does permit reimbursement for certain off-label uses of FDA-approved drugs or biologicals

employed in an anticancer chemotherapeutic regimen if such use is included in a recognized compendium or if the local

Medicare contractor determines it to be medically accepted based on clinical evidence from peer-reviewed literature

recognized by the HHS Secretary. See § 1861(t) of the Social Security Act, 42 U.S.C. § 1395x(t).

127

Marchese, complaint, at 6, 19, 25.

128

Marchese, complaint in intervention, at 15. The government alleged that Cell Therapeutics “caused a series of

separate false statements to be made to medical directors working for Medicare program carriers to try to obtain

Medicare reimbursement for off-label uses of Trisenox.” Id. at 2.

129

Id.

122

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of Justice settled the case for $10.5 million, plus interest, in April 2007, without the company

admitting wrongdoing, but rather asserting that its “statements were a consequence of negligent

advice provided” by an outside party.130

In another FCA suit, Jazz Pharmaceuticals, Inc., settled with the Department of Justice for $20

million in civil and criminal penalties and restitution in July 2007. This FCA suit was brought by

a former sales representative and addressed the company’s promotion of Xyrem—a drug also

known as the date-rape drug or GHB (gamma-hydroxybutyrate)—for off-label uses other than the

two approved medical uses related to narcolepsy.131 The company’s subsidiary pled guilty to

criminal misbranding under the FFDCA, through which it led doctors to prescribe Xyrem though

such prescriptions were not reimbursable by private insurers, Medicare, or Medicaid.132 The

Xyrem case also concerned the distribution of documents regarding unapproved new uses that did

not follow FDA guidance regarding manufacturer promotion.133

Interaction of the FDA Guidance with the False Claims Act

One question that arises in the context of promotion of off-label drug uses is whether the new

FDA guidance might be used to create a safe harbor for pharmaceutical companies if they are

sued under the FCA. Although the guidance document is not a statute and may not be binding,

this report will first analyze it as if it created a question of statutory construction, as this may help

to show how a court may view the role of the guidance document in a FCA case based on

marketing or promotion by a pharmaceutical company that arguably falls within the purported

safe harbor of the guidance document.134

Conflicts frequently arise between the operation of two federal statutes that are silent as to their

relationship. In such a case, courts will try to harmonize the two so that both can be given effect.

A court “must read [two allegedly conflicting] statutes to give effect to each if [it] can do so while

preserving their sense and purpose.”135 Only if provisions of two different federal statutes are

“irreconcilably conflicting,”136 or “if the later act covers the whole subject of the earlier one and

is clearly intended as a substitute,”137 will courts apply the rule that the later of the two prevails.

“[R]epeals by implication are not favored, ... and will not be found unless an intent to repeal is

clear and manifest.”138 Generally, if Congress intends one statute to repeal an earlier statute or

section of a statute, or intends the earlier statute to remain in effect, it usually says so directly in

the repealing act.

130

United States ex rel. James Marchese v. Cell Therapeutics, Inc., Civil Action No. 06-168-MJP (W.D. Wash.

stipulation of dismissal and motion to lift seal filed Apr. 16, 2007), at 4.

131

United States ex rel. Lauterbach v. Orphan Medical Inc., Civ. Action No. 05-00387 (E.D.N.Y. settlement announced

July 13, 2007).

132

The United States Attorney’s Office, Eastern District of New York, Press Release, Jazz Pharmaceuticals, Inc.

Agrees to Pay $20 Million to Resolve Criminal and Civil Allegations in “Off-Label” Marketing Investigation, July 13,

2007, http://www.usdoj.gov/usao/nye/pr/2007/2007jul13a.html.

133

Id.

134

For more information, see CRS Report 97-589, Statutory Interpretation: General Principles and Recent Trends.

135

Watt v. Alaska, 451 U.S. 259, 267 (1981).

136

Watt, 451 U.S. at 266.

137

Posadas v. National City Bank, 296 U.S. 497, 503 (1936).

138

Rodriguez v. United States, 480 U.S. 522, 524 (1987) (citations omitted); see also Morton v. Mancari, 417 U.S. 535,

550-51 (1974).

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FDA Guidance Regarding the Promotion of Off-Label Uses of Drugs: Legal Issues

In a case that is roughly analogous to the current inquiry regarding the interaction of a guidance

document and the FCA, a federal court’s decision in the FCA qui tam suit United States ex rel.

R.C. Taylor III v. Mario Gabelli may be instructive.139 In that case, the defendants argued that a

remedial scheme promulgated by the Federal Communications Commission (FCC) for violations

of the agency’s regulations preempted the FCA and therefore the whistleblower could not apply

the FCA to false statements made to the agency.140 The court noted that repeals by implication are

disfavored, but that more detailed statutes may indicate Congress’s intent to override more

general ones in the area of federal claims and statutory remedies.141 The court further explained

that

courts have been ‘reluctant to find pre-emption of the [FCA] even where other laws provided

closely related regulation and remedies.’142 Indeed, the legislative history indicates that

Congress specifically contemplated the use of the Act to address regulatory violations.143

The court found that the defendants did not show, from the legislative history or otherwise, that

Congress meant to override the remedies available in the FCA when Congress delegated its

authority to create a remedial scheme to the FCC.144

The court also examined whether the FCC’s more specific remedial scheme would preempt the

FCA because the agency’s remedies were more detailed than those in the FCA.145 It held that the

FCC regulations and the FCA were not in conflict, even if the FCC remedial scheme offered a

more detailed remedy than the FCA.146 Therefore, the court concluded that Congress did not

intend “to preclude FCA claims by authorizing the FCC to grant relief for violations of FCC

regulations.”147

Assuming that the FDA has the authority to issue guidance on the dissemination of reprints since

the expiration of the relevant FDAMA provisions, and that a reviewing court would use reasoning

similar to that in Gabelli, it appears unlikely that a court would find that Congress intended to

preempt the FCA when it delegated general rulemaking authority to the FDA and enacted general

statutes relating to guidance issued by the FDA, which the FDA then used to issue its guidance.

Whistleblowers in qui tam cases have used the FCA to address false claims that stem from

regulatory violations of misbranding, and, as the court noted above, the FCA’s legislative history

shows that Congress had contemplated using the FCA this way.148 Additionally, as a court noted

in a case specifically relating to the dissemination provisions under FDAMA, “the FDA’s

139

United States ex rel. R.C. Taylor III v. Mario Gabelli, 345 F. Supp. 2d 313, 333 (S.D.N.Y. 2004)

Id. at 332. The court noted its use of the term “preempt” was atypical because the term preemption does not

generally involve two federal laws, but rather a federal law and a state law. Id. at 333 n. 112.

141

Id. at 333-34 (quoting United States ex rel. Fallon v. Accudyne Corp., 880 F. Supp. 636, 639 (W.D. Wis. 1995)).

142

Id. at 334 (quoting United States ex rel. Fallon v. Accudyne Corp., 880 F. Supp. 636, 639 (W.D. Wis. 1995)).

143

Id.

144

Id.

145

Id.

146

Id.

147

Id. at 334-35.

148

Id. at 334 n.121 (quoting S. Rep. No. 99-345, reprinted in 1986 U.S. Code Cong. and Admin. News at 5274: “A

false claim [under the act] may take many forms, the most common being a claim for goods or services not provided, or

provided in violation of ... statute[] or regulation.”).

140

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prosecutorial power flows from its long established authority to prosecute manufacturers for

misbranding, not from the newly created [now expired] FDAMA” provisions.149

Therefore, while the FDA’s guidance may indicate how the agency intends to wield its

enforcement powers with respect to pharmaceutical manufacturers—because it provides them

with the FDA’s “current views and recommendations” regarding dissemination of reprints

regarding off-label uses—the agency itself has stated that the “FDA’s legal authority to determine

whether distribution of medical or scientific information constitutes promotion of an unapproved

‘new use’ or whether such activities cause a product to violate the [FFDCA] has not changed.”150

This comment echoes the position taken by the FDA in a Federal Register notice,151 in which the

agency indicated that it could determine a manufacturer’s intent on a case-by-case enforcement

basis using its longstanding statutory authorities.152 Nor would the FDA’s guidance affect the

legal authority, enforcement powers, or other capabilities of outside agencies that have been

involved in prosecuting FCA cases related to off-label marketing, such as the HHS Office of

Inspector General, the Federal Bureau of Investigation, and the Department of Justice.153

With regard to cases brought under statutory provisions of the FFDCA, under the guidance, the

FDA’s ability to use dissemination of materials regarding off-label or new uses of a drug as

evidence in establishing the manufacturer’s intent that the drug be used for a new, unapproved use

would not appear to change, either. The FDA could still proceed on a case-by-case basis, using

the guidance as a safe harbor for manufacturers who follow it: “if a manufacturer follows the

recommendations described ... FDA does not intend to consider the distribution of such medical

and scientific information ... as establishing intent that the product be used for an unapproved new

use,” which would result in a product being misbranded.154 But if a manufacturer unlawfully

promoted a drug, it appears that dissemination of materials regarding off-label use could be used

as evidence of intent and could lead to an enforcement action.155 The guidance also appears to

indicate that unlawful promotion of a drug would invalidate a case where the manufacturer

followed the guidance recommendations but illegally promoted a drug. Furthermore, even if the

manufacturer’s promotion of an off-label use of a drug fell within the safe harbor of the FDA

guidance document, FCA suits may still arise. The off-label use of the drug may still not be

covered for reimbursement under federal programs such as Medicaid because the off-label use of

the drug would not be for a medically accepted indication (i.e. an FDA-approved use or an offlabel use included in a specified drug compendia).156

149

Washington Legal Foundation v. Henney, 128 F. Supp. 2d 11, 13 (D.C. Cir. 2000).

Guidance Notice, supra note 1 (emphasis added); Guidance, supra note 3.

151

“If section 401 did not exist, the government could use such dissemination [of materials regarding the off-label or

“new use” of a drug] as evidence in establishing a manufacturer’s illegal distribution of a new drug for a “new use,”

and in establishing that the product is misbranded.” FDA, Notice: Decision in Washington Legal Foundation v.

Henney, 65 Fed. Reg. 14286, 14287 (Mar. 16, 2000).

152

Id. at 14286. The FDA states that, at oral argument in the case, “[p]laintiff Washington Legal Foundation (WLF)

expressly agreed that FDA may proceed on a case-by-case basis under pre-FDAMA enforcement authority.” Id. at

14287.

153

Guidance Notice, supra note 1.

154

Guidance, supra note 3.

155

Id.

156

See text accompanying note 105; see also Medicaid drug coverage provisions at 42 U.S.C. § 1396r-8(K), including

coverage for off-label drugs listed in specified compendia at 42 U.S.C. § 1396r-8(g)(1)(B)(i).

150

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Author Contact Information

(name redacted)

Legislative Attorney

[redacted]@crs.loc.gov, 7-....

Acknowledgments

(name redacted), former Legislative Attorney, was an author of this report.

Congressional Research Service

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