Off-label

An off-label use of a drug means using an FDA-approved drug for an unapproved use.

Estimates are that 21% of all prescriptions are off-label, and an even higher percentage of 36.2% of medications in intensive care units are off-label. "One study estimated that 21 percent of drugs prescribed by office-based physicians were for off-label uses." See U.S. Gov't Accountability Office, Medicare Part D: Plan Sponsors' Processing and CMS Monitoring of Drug Coverage Requests Could be Improved, GAO 08-47, 15 n.26 (2008) (citing D. Radley, et. al., Off-Label Prescribing Among Office-Based Physicians, 166 Archives of Internal Med. (May 8, 2006))[1]

As of September 25, 2022, a total of 2,719 decisions (2,250 federal) have referenced the term "off-label". Of those, only 231 decisions (196 federal) discuss the FDA in proximity with the "off-label" term, and many of those cases are class action product liability cases, qui tam actions under the False Claims Act, and disputes over laws against promoting off-label uses.

## Contents

* 1 Background
* 1.1 Devices
* 2 See also
* 3 References

## Background[edit]

“  |  This reading of the Authorization comports with the background understanding of the Federal Food, Drug, and Cosmetic Act. The Act regulates drug distribution; it does not bar doctors from prescribing an approved drug (like hydroxychloroquine) for an off-label use (like COVID-19). See Caronia, 703 F.3d at 153. The Association's complaint thus alleges that the Act permits off-label prescriptions. Compl., R.1, PageID 5-6. And the FDA even acknowledged this narrow reading of the Authorization's scope on appeal. Appellees' Br. 21; cf. Driehaus, 573 U.S. at 165.  |  ”

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Ass'n of Am. Physicians & Surgs v. United States FDA, 13 F.4th 531, 544 (6th Cir. 2021).

“  |  e) Off-Label Use

The FDA policy of regulating drugs and not the practice of medicine has been consistent since the creation of the agency in 1983 by the enactment of the FDCA. This policy was noted by the FDA at the 1991 advisory committee. See Advisory Committees, infra, III(f). "The FDA's job and legal mandate is not to regulate the practice of medicine but simply to regulate the availability of medications to the practicing population at large." Transcript of Fertility and Maternal Health Drugs Advisory Committee, meeting, 46:17-20 (June 20, 1991). Allowing physicians to prescribe for off-label use "is an accepted and necessary corollary of the FDA's mission to regulate in this area without directly interfering with the practice of medicine." Buckman Co. v. Plaintiffs' Legal Comm., 531 U.S. 341, 350, 121 S. Ct. 1012, 148 L. Ed. 2d 854 (2001) (discussing FDA regulation of medical devices).

Off-label activity has been defined by the FDA as a "use for indication, dosage form, dose regimen, population or other use parameter not mentioned in the approved labeling." Janet Woodcock, M.D., A Shift In The Regulatory Approach, PowerPoint, at slide 3 (June 23, 1997) at http://www.fda.gov/cder/present/diamontreal/regappr/sld003.htm) (last visited July 3, 2008). Off-label prescribing of drugs is both legal and ethical. The New Jersey Legislature declared "'off-label' use of an FDA-approved drug [to be] legal when prescribed in a medically appropriate way." N.J.S.A. 26:1A-36.9(e).

The FDA has long acknowledged that undue restrictions on off-label use could have adverse health consequences. In 1982, the FDA Drug Bulletin informed the medical community that "[o]nce a [drug] product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling." 12 FDA Drug Bulletin 4, 5 (1982). The agency went on to state that

'unapproved' or more precisely 'unlabeled' uses may be appropriate and rational in certain circumstances, and may, in fact reflect approaches to drug therapy that have been extensively reported in medical literature .. . Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations.

[Id. at 5.]

Following the accepted medical standard of care, physicians frequently prescribe drugs for off-label or unapproved uses.

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Bailey v. Wyeth, Inc., 2008 N.J. Super. Unpub. LEXIS 3004, *17-19.

> "even the FDA has acknowledged that off-label use of a drug may be appropriate and rational (see Use of Approved Drugs for Unlabeled Indicators, FDA Drug Bulletin (Public Health Service, Md.) April 1982, vol. 12, No. 1, 4-5)."

Proctor v. Davis, 291 Ill. App. 3d 265, 295, 225 Ill. Dec. 126, 146, 682 N.E.2d 1203, 1223 (1997) (dissent).

“  |  Despite the increased federal scrutiny of new drugs, important aspects of patient access to drugs are unregulated by the government and appear always to have been unregulated. The "FDA's regulatory authority . . . extends to manufacturers of drugs but not to the physicians who dispense them." 14 Thus, a doctor may -- and approximately 21% of the time does -- prescribe a drug to a patient for a purpose other than that for which the FDA has approved the use of the drug. 15 Such "off-label" use may occur even if the drug is not deemed safe or effective for that use, such as when a drug studied only for adults is prescribed for a child. Further, it appears that the FDA has never prohibited either off-label prescription or off-label use of drugs. 16 In recent years, the FDA has been moving to permit drug manufacturers to promote the use of their drugs for off-label purposes in limited circumstances. 17 See Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, 111 Stat. 2296 (codified in scattered sections of 21 U.S.C. §§ 301-81).

For more than half of this Nation's history, then, until the enactment of the 1906 Act, a person could obtain access to any new drug without any government interference whatsoever. Even after enactment of the FDCA in 1938, Congress imposed no limitation on the commercial marketing of new drugs based upon the drugs' efficacy. Rather, at that time, the FDA could interrupt the sale of new drugs only if it determined that the new drug was unsafe. Government regulation of such drugs premised on concern over a new drug's efficacy, as opposed to its safety, is of very recent origin. Even today, a patient may use a drug for unapproved purposes where the drug may be unsafe or ineffective for the off-label purpose. In short, encumbrances on the treatment decisions of a patient and her physician lack the historical pedigree of the rights that the Alliance seeks to vindicate.

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Abigail All. for Better Access to Developmental Drugs v. Von Eschenbach, 378 U.S. App. D.C. 33, 63-64, 495 F.3d 695, 725-26 (2007) (Rogers, J., dissenting)

> Physicians may, in their professional judgment, prescribe a drug for a purpose other than that for which it has been approved by the FDA. (Buckman Co. v. Plaintiffs' Legal Comm. (2001) 531 U.S. 341, 351, fn. 5 [148 L.Ed.2d 854, 121 S.Ct. 1012] [“‘Off-label use is widespread in the medical community’”].)

T.H. v. Novartis Pharm. Corp., 4 Cal. 5th 145, 158 n.1, 226 Cal. Rptr. 3d 336, 342, 407 P.3d 18, 24 (2017)

> Initially we note that although the FDA regulates, among other things, drugs and medical devices, the FDA does not regulate the practice of medicine. The legislative history of the federal Food, Drug and Cosmetic Act reveals that Congress recognized that the act was "not intended as a medical practices act and [would] not interfere with the practice of the healing art ***." S.Rep.No.36l, 74th Cong., 1st Sess. at 3 (1935).

> In conformity with this legislative intent, courts addressing FDA regulated drug issues have determined that physicians are permitted to use federally approved drugs as they, in their medical judgment, see fit. This professional latitude was recognized in Weaver v. Reagen (C.A. 8, 1989), 886 F.2d 194, where the court stated at 198:

> Contrary to defendants' assertions, FDA approved indications were not intended to limit or interfere with the practice of medicine nor to preclude physicians from using their best judgment in the interest of the patient. ***

> The [Food, Drug and Cosmetic] Act does not, *** limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling. "Use of Approved Drugs for Unlabeled Indications," 12 FDA Drug Bulletin 4 (April (1982).

> Thus, the decision whether or not to use a drug for an off-label purpose is a matter of medical judgment not of regulatory approval. By analogy, the off-label use of a medical device is also a matter of medical judgment, and as such, subjects a physician to professional liability for exercising professional medical judgment. Off-label use of a medical device is not a material risk inherently involved in a proposed therapy which a physician should have disclosed to a patient prior to the therapy. See Nickel 1, supra. Therefore, since Biscup engaged in off-label use of this medical device he could be subject to professional liability for medical negligence, but in this case those claims have been litigated and are not before us. Accordingly, we conclude failure to disclose FDA status does not raise a material issue of fact as to informed consent.

Klein v. Biscup, 109 Ohio App. 3d 855, 863-64, 673 N.E.2d 225, 231 (1996)

> However, physicians may exercise their independent medical judgment to prescribe FDA-approved drugs to treat conditions other than those for which the drug is approved, if appropriate for the particular patient.25 Absent state regulation, once a drug has been approved by FDA, doctors may prescribe it for indications and in dosages other than those expressly approved by the FDA. This is a widely employed practice known as "off-label" use. Off-label use does not violate federal law or FDA regulations because the FDA regulates the marketing and distributing of drugs in the United States, not the practice of medicine, which is the exclusive realm of the individual states.

Goico v. United States FDA, No. 20-1248-JAR-KGG, 2020 U.S. Dist. LEXIS 226868, at *8-9 (D. Kan. Dec. 3, 2020).

> See Wash. Legal Found. v. Friedman, 13 F. Supp. 2d 51, 56 (D.D.C.1998) ("[O]ff-label use of FDA-approved drugs by physicians is an established aspect of the modern practice of medicine."), vacated in part on other grounds, Wash. Legal Found. v. Henney, 202 F.3d 331, 340 U.S. App. D.C. 108 (D.C. Cir. 2000).

United States v. Regenerative Scis., LLC, 878 F. Supp. 2d 248, 261 n.11 (D.D.C. 2012)

### Devices[edit]

> Moreover, the FDA's "approval process generally contemplates that approved [devices] will be used in off-label ways," United States v. Caronia, 703 F.3d 149, 166 (2d Cir. 2012); see also Caplinger v. Medtronic, Inc., 921 F. Supp. 2d 1206, 1218 n.3 (W.D. Okla. 2013) (noting that off-label use is not illegal or disfavored but an accepted and valuable part of the practice of medicine). Off-label use may even be a recognized standard of care. Caronia, 703 F.3d at 153. And congress has prohibited the FDA from "limit[ing] or interfer[ing] with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease." 21 U.S.C. § 396 (2014). Although the Infuse Device was approved as a system, the statutory definition supports our conclusion that each component is a "device" under the FDA that must follow specific federal requirements. See Riley v. Cordis Corp., 625 F. Supp. 2d 769, 780 (D. Minn. 2009) ("It makes no sense—indeed, it would probably be impossible—to pick apart the components of a medical device and apply different preemption analyses to different components."). Consequently, we conclude that the FDA established specific federal requirements for the Infuse Device, even when the Infuse Protein is used alone.

Angeles v. Medtronic, Inc., 863 N.W.2d 404, 411-12 (Minn. Ct. App. 2015).

> It recognized that "physicians have the right, exercising reasonable medical judgment, to use medical devices for off-label purposes that are not FDA approved, provided that the FDA has approved the device for some other purpose." Id. (citing Staudt v. Froedtert Mem'l Lutheran Hosp., 217 Wis. 2d 773, 580 N.W. 2d 361, 362-63 (Wis. Ct. App. 1998)).

Seavey v. Globus Med., Inc., No. 11-2240 (RBK/JS), 2014 U.S. Dist. LEXIS 65985, at *47-48 (D.N.J. Mar. 11, 2014)

> What is clear is that the FDA's concern is to regulate the marketing and labeling of medical devices, not to intrude upon the practice of medicine or redefine the doctrine of informed consent. Significantly, the FDA does not prohibit off-label use of pedicle screws. In essence, physicians have the right, exercising reasonable medical judgment, to use medical devices for off-label purposes that are not FDA approved, provided that the FDA has approved the device for some other purpose. Staudt v. Froedtert Mem'l Lutheran Hosp., 217 Wis. 2d 773, 580 N.W.2d 361, 362-63 (Wis.Ct.App.1998). In this case defendant testified, without contradiction, that the use of pedicle screws was generally accepted in the field of spinal surgery in 1990. Of course, "'a physician who engages in off-label uses has the responsibility to be well informed about the device, and to base the decision to use it on sound medical evidence. . . .'" Femrite v. Abbott Northwestern Hosp., 568 N.W.2d 535, 542 (Minn.Ct.App.1997) (quoting FDA document dated February 17, 1994, entitled "Update on the Regulatory Status of Pedicle Screws").

Blazoski v. Cook, 346 N.J. Super. 256, 272, 787 A.2d 910, 919-20 (Super. Ct. App. Div. 2002)

> (not a quote) lack of FDA approval does not prohibit a physician from "off label" use

Kirkman v. Sofamor, S.N.C., 1998 U.S. Dist. LEXIS 13357, 1998 WL 666706 at *4 (W.D. N.C. July 21, 1998)

## See also[edit]

Steven R. Salbu, Off-Label Use, Prescription, and Marketing of FDA-Approved Drugs: An Assessment of Legislative and Regulatory Policy, 51 FLA. L. REV. 181, 189-92 (1999); see Chaney v. Heckler, 231 U.S. App. D.C. 136, 718 F.2d 1174, 1180 (D.C. Cir. 1983), rev'd on other grounds, 470 U.S. 821, 105 S. Ct. 1649, 84 L. Ed. 2d 714 (1985).

## References[edit]

1. ↑ http://www.gao.gov/new.items/d0847.pdf. Bailey v. Wyeth, Inc., 2008 N.J. Super. Unpub. LEXIS 3004, *19.