Free Speech Amarin and First Amendment Challenges

Transcription

1 Free Speech Amarin and First Amendment Challenges Lisa M. Baird Gillian H. Clow Reed Smith LLP 355 South Grand Avenue, Suite 2900 Los Angeles, CA (213) Rita A. McConnell Medtronic, Inc. 710 Medtronic Parkway Minneapolis, MN 55432

2 Lisa M. Baird is a product liability attorney in Reed Smith s Life Sciences Health Industry Group with 20 years of experience defending medical device and pharmaceutical clients in individual and mass tort litigation. She is a long-time member of the DRI Drug and Medical Device Committee as well as the Pro Bono Appeals chair of the DRI Appellate Advocacy Committee. Gillian H. Clow is an associate in in Reed Smith s Complex Litigation Group. She received her J.D. from Loyola Law School, Los Angeles, in 2014, and was elected to the Order of the Coif. While in law school, Ms. Clow was an editor of the Loyola of Los Angeles Entertainment Law Review and a member of the Willem C. Vis International Commercial Arbitration Moot Team. Rita A. McConnell is vice president and chief litigation counsel for Medtronic, a global health care solutions company committed to improving lives through medical technologies, services and solutions. Ms. McConnell leads the team responsible for managing the company s portfolio of product liability, commercial, securities, and employment litigation. During her career, Ms. McConnell has represented both private and public sector clients in state and federal court trials, arbitrations, and administrative hearings in commercial and employment litigation. She also has extensive experience managing complex product liability and class actions as well as competitive practices and trade secret litigation.

3 Free Speech Amarin and First Amendment Challenges Table of Contents I. Introduction...5 II. Article...5 Free Speech Amarin and First Amendment Challenges Baird et al. 3

4

5 Free Speech Amarin and First Amendment Challenges I. Introduction The following article explores the current state of the law regarding government restrictions on offlabel promotion, and First Amendment free speech limitations on such restrictions. Section I discusses off-label use and promotion, and federal laws, regulations, and guidance documents limiting permissible off-label promotion by medical device and pharmaceutical manufacturers. Section II provides a short introduction to key First Amendment free speech basics, including relevant Supreme Court decisions regarding First Amendment protections for commercial speech and the level of scrutiny to be applied when governmental restrictions on speech are content-based. Section III then looks at recent lower court First Amendment decisions limiting FDA restrictions on off-label promotion, including the notable recent decision, Amarin Pharma, Inc. v. United States Food & Drug Admin., 119 F. Supp. 3d 196 (S.D.N.Y. 2015). Section IV concludes the article by analyzing these issues in the product liability and litigation context. It summarizes how off-label promotion allegations are used by the plaintiffs bar to support failure to warn and other claims, and how First Amendment free speech arguments can be used by defendants to limit these theories and arguments. II. Article Free Speech: Amarin and First Amendment Challenges Lisa M. Baird Gillian H. Clow Reed Smith LLP 355 South Grand Avenue Suite 2900 Los Angeles, CA (213) lbaird@reedsmith.com gclow@reedsmith.com Rita A. McConnell Vice President and Chief Litigation Counsel Medtronic, Inc. 710 Medtronic Parkway Minneapolis, MN Free Speech Amarin and First Amendment Challenges Baird et al. 5

6 TABLE OF AUTHORITIES Page(s) Cases In re Actimmune Mktg. Litig., 614 F. Supp. 2d 1037 (N.D. Cal. 2009), aff d 464 Fed. Appx. 651 (9th Cir. 2011)...5 Alton v. Medtronic, Inc., 2013 WL (D. Or. Sept. 6, 2013)...6 Amarin Pharma, Inc. v. United States Food & Drug Admin., 119 F. Supp. 3d 196 (S.D.N.Y. 2015)... passim American School of Magnetic Healing v. McAnnulty, 187 U.S. 94 (1902)...11 Beavers-Gabriel v. Medtronic, Inc., 15 F. Supp. 3d 1021, 1041 (D. Haw. 2014)...27 Bolger v. Youngs Drug Prods. Corp., 463 U.S. 60 (1983)...10 Bracco Diagnostics, Inc. v. Amersham Health, Inc., 627 F. Supp. 2d 384 (D.N.J. 2009)...11 Buckman Co. v. Plaintiffs Legal Comm., 531 U.S. 341 (2011)...3, 27 Caplinger v. Medtronic, Inc., 784 F.3d 1335 (10th Cir. 2015)...3 Caronia v. United States, 703 F.3d 149 (2d Cir. 2012)... passim Carson v. Depuy Spine, Inc., 365 Fed. Appx. 812 (9th Cir. 2010)...26 Central Hudson Gas & Elec. Corp. v. Pub. Serv. Comm n of N.Y., 447 U.S. 557 (1980)... passim Cline v. Oklahoma Coalition for Reproductive Justice, 313 P.3d 253 (Okla. 2013)...4, 5 Coleman v. Medtronic, Inc., 223 Cal. App. 4th 413 (2014)...3, 6 - i - 6 Drug and Medical Device May 2016

7 Cox v. Depuy Motech, Inc., 2000 WL (S.D. Cal. Mar. 29, 2000)...26 In re Epogen & Aranesp Off-Label Mktg. & Sales Practices Litig., 590 F. Supp. 2d 1282 (C.D. Cal. 2008)...5 FCC v. Fox Television Stations, Inc., 132 S. Ct (2012)...26 Gavin v. Medtronic, Inc., 2013 WL (E.D. La. July 19, 2013)...27 Gertz v. Robert Welch, Inc., 418 U.S. 323 (1974)...11 Kashani Matts v. Medtronic, 2013 WL (C.D. Cal., Nov. 22, 2013)...27 Martin v. Medtronic, Inc., 32 F. Supp. 3d 1026, 1041 (D. Ariz. 2014)...27, 28 McMillan v. Togus Regional Office, 294 F. Supp. 2d 305 (E.D.N.Y. 2003)...11 Metabolife International, Inc. v. Wornick, 72 F. Supp. 2d 1160 (S.D. Cal. 1999), aff'd in pertinent part, rev'd in part, 264 F.3d 832 (9th Cir. 2001)...11 Miller v. California, 413 U.S. 15 (1973)...11 Morris v. Minnesota Mining & Mfg. Co., 2015 WL (D. Md. Apr. 16, 2015)...28 In re Neurontin Marketing & Sales Pract. Litig., 712 F. 3d 21 (1st Cir. 2013)...18 Neurotron, Inc. v. American Ass'n of Electrodiagnostic Medicine, 189 F. Supp. 2d 271 (D. Md. 2001) aff d, 48 Fed. App x. 42 (4th Cir. 2002)...11 ONY Corp. v. Cornerstone Therapeutics, Inc., 720 F.3d 490 (2d Cir. 2013)...11 Pacira Pharma., Inc. v. United States Food & Drug Admin., Case No. 1:15-cv (filed Sept. 9, 2015)...23, 29 - ii - Free Speech Amarin and First Amendment Challenges Baird et al. 7

8 Perez v. Nidek Co., 711 F.3d 1109 (9th Cir. 2013)...27 Planned Parenthood Arizona, Inc. v. Humble, 753 F.3d 905 (9th Cir. 2014)...3 Pom Wonderful LLC v. Federal Trade Commission, 773 F.3d 478 (D.C. Cir. Jan. 30, 2015)...22 Raab v. Smith & Nephew, Inc., F. Supp. 3d, 2015 WL (S.D.W. Va. Dec. 15, 2015)...5, 28 Reed v. Town of Gilbert, 135 S. Ct (2015)...10, 13, 14, 15 Reeves v. AcroMed Corp., 44 F.3d 300 (5th Cir. 1995)...2 Riley v. Cordis Corp., 625 F. Supp. 2d 769 (D. Minn. 2009)...5, 28 Riley v. National Federation of the Blind, Inc., 487 U.S. 781 (1988)...11 Schouest v. Medtronic, Inc., 13 F. Supp. 3d 692, 702 (S.D. Tex. 2014)...5 Solis v. Millennium Pharmaceuticals, 09-cv-3010 (E.D. Cal., Mar. 27, 2015)...22 Sorrell v. IMS Health Inc., 131 S. Ct (2011)... passim U.S.A. v. Vascular Solutions, Inc., et al., No. 5:14-cr (W.D. Tex.) (filed Aug. 13, 2015)...9 Underwager v. Salter, 22 F.3d 730 (7th Cir. 1994)...11 United States v. Caronia, 703 F.2d 149 (2d Cir. 2012)...22 United States v. Harkonen, 2009 WL (N.D. Cal. June 4, 2009)...11 Vess v. Ciba-Geigy Corp. USA, 317 F.3d 1097 (9th Cir. 2003) iii - 8 Drug and Medical Device May 2016

9 Wallach v. Crawford, 2005 WL (S.D. Cal. Mar. 29, 2005)...11 Wilson v. Frito-Lay North America, Inc., 961 F.Supp.2d 1134 (N.D. Cal. Oct. 24, 2013)...26 Statutes 21 U.S.C. 331(a)...6, 16, U.S.C. 333(a)(2)...6, 16, U.S.C. 337(a) U.S.C. 352(a)-(n) U.S.C. 352(f) U.S.C. 355(a), (d) U.S.C. 360c(a) U.S.C Regulations 21 C.F.R C.F.R (c)(6)(i) C.F.R (e) C.F.R C.F.R , 6, 7 21 C.F.R C.F.R Other Authorities A. Tauber, The First Amendment Does Not Undermine The Preemption Of Medical-Device Failure-To-Warn Suits, Vol., No C. P. Guzelian, Scientific Speech, 93 Iowa L. Rev. 881, 906 (2008) iv - Free Speech Amarin and First Amendment Challenges Baird et al. 9

10 E. Zaret, Commercial Speech and the Evolution of the First Amendment...11 L Bograd, Be Careful What You Wish For: Drugmakers, The First Amendment, And Preemption, 51 TRIAL 24 (Nov. 2015)...27 Memorandum of the AMA House of Delegates, Resolution 820, Off-Label Use of Pharmaceuticals (Sept. 21, 2005)...4 Regulating Off-Label Drug Use: Rethinking the Role of the FDA, 358 N. Engl. J. Med. 1427, 1427 (2008)...4 U.S. Food & Drug Admin., FDA Drug Bulletin, 12 FDA Drug Bull. 1, 5 (1982)...3, 4 U.S. Food & Drug Admin., Draft Guidance, 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 (2009)...7, 8 U.S. Food & Drug. Admin, Guidance for Industry: Industry- Supported Scientific And Educational Activities (1997)...7,8 U.S. Food & Drug Admin., Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses Recommended Practices (2014)...7, 8 U.S. Food & Drug Admin., Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs & Medical Devices (2011)...4, 8, 9 Brief for the United States filed in United States v. Caronia, Nos , , 2010 WL (2d Cir., filed Oct. 8, 2010)...9 Proposed Jury Instructions for the United States filed in United States v. Vascular Solutions, No. 14-cr-926 (W.D. Tex. Jan. 27, 2016)...10 Woodcock M.D., Janet, Presentation, CDER 2016 Priorities v - 10 Drug and Medical Device May 2016

11 SUMMARY This article explores the current state of the law regarding government restrictions on off-label promotion, and First Amendment free speech limitations on such restrictions. Section I discusses off-label use and promotion, and federal laws, regulations, and guidance documents limiting permissible off-label promotion by medical device and pharmaceutical manufacturers. Section II provides a short introduction to key First Amendment free speech basics, including relevant Supreme Court decisions regarding First Amendment protections for commercial speech and the level of scrutiny to be applied when governmental restrictions on speech are content-based. Section III then looks at recent lower court First Amendment decisions limiting FDA restrictions on off-label promotion, including the notable recent decision, Amarin Pharma, Inc. v. United States Food & Drug Admin., 119 F. Supp. 3d 196 (S.D.N.Y. 2015). Section IV concludes the article by analyzing these issues in the product liability and litigation context. It summarizes how off-label promotion allegations are used by the plaintiffs bar to support failure to warn and other claims, and how First Amendment free speech arguments can be used by defendants to limit these theories and arguments Free Speech Amarin and First Amendment Challenges Baird et al. 11

12 I. Government Restrictions Regarding Speech About Off-Label Uses Of Medical Devices And Pharmaceuticals The off-label concept for medical devices and drugs stems from the fact that under the Federal Food, Drug and Cosmetic Act ( FDCA ), the FDA reviews the safety and efficacy of drugs and medical devices with respect to a particular intended use when deciding whether the product can be sold, and then requires that intended use to be identified on the labeling. For devices, the Medical Device Amendments ( MDA ) to the FDCA set up a device classification scheme requiring premarket approval or an exemption, and safety and efficacy are determined with respect to the intended population and the conditions for use indicated in labeling. 21 U.S.C. 360c(a). For drugs, the FDCA provides that [n]o person shall introduce or deliver for introduction into interstate commerce any new drug, unless an approval of an application filed pursuant to subjection (b) or (j) of this section is effective with respect to such drug, and to gain FDA approval, the manufacturer must demonstrate that the drug is safe and effective for the intended use or indication. 21 U.S.C. 355(a), (d). 1 A. The FDA Does Not Regulate The Practice Of Medicine Once a device or drug is lawfully available, physicians may use it for any treatment deemed medically necessary and appropriate for a particular patient. Federal law does not give FDA the authority to regulate the practice of medicine. With respect to devices, 21 U.S.C. 396 provides that nothing in the MDA shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device for any condition or disease within a legitimate health care practitioner-patient relationship. And with respect to drugs, the FDA has stated that [o]nce 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. U.S. Food & Drug Admin., FDA Drug Bulletin, 12 FDA Drug Bull. 1, 5 (1982). 1 Although the term off label seems to suggest that the use in question is one that is not mentioned on the FDA-approved label at all, the FDA can and does require manufacturers to include warnings and risk information on the label about uses different from those listed in the indications for use. See, e.g., 21 C.F.R (e), (c)(6)(i) (FDA may require a warning relating to a use not identified in the Indications and Usage section of a drug label); Reeves v. AcroMed Corp., 44 F.3d 300, (5th Cir. 1995) ( FDA labeling regulations specifically address off-label uses of medical devices. For example, FDA regulations require manufacturers to provide appropriate labeling if the manufacturer has reason to believe that its medical device might be used for purposes different from the purposes for which the device is approved. 21 C.F.R Similarly, the FDA can require a manufacturer to provide additional labeling that addresses potential off-label uses. 21 C.F.R ) Drug and Medical Device May 2016

13 Thus, 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 (2011); see also Caronia v. United States, 703 F.3d 149, 153 (2d Cir. 2012) (quoting Buckman); Coleman v. Medtronic, Inc., 223 Cal. App. 4th 413, 423 (2014) ( Nothing in the MDA prevents a doctor from using a medical device in an offlabel manner. ). As one court put it, the FDA not only expects off-label use but encourages it as part of the effective practice of medicine. Planned Parenthood Arizona, Inc. v. Humble, 753 F.3d 905, 915 (9th Cir. 2014). The FDA itself has recognized that [o]ff-label uses of treatment regimens may be important and may even constitute a medically-recognized standard of care. Caronia, 703 F.3d at 153, quoting U.S. Food & Drug Admin., Draft Guidance, 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, 3 (2009). The FDA also has recognized that [g]ood medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. U.S. Food & Drug Admin., Off Label & Investigational Use Of Marketed Drugs, Biologics & Medical Devices- Information Sheet, Guidance for Institutional Review Boards and Clinical Investigators. 2 Congress had good reason to limit FDA authority in this respect. [O]fflabel uses often prove[s] vital to patients and [Congress was] wary about granting the federal government the power to deny doctors and patients the freedom to use approved devices in any way they think might help improve health or extend life. Caplinger v. Medtronic, Inc., 784 F.3d 1335, 1344 (10th Cir. 2015). While off-label use may be the most common term for this practice, it is not the only one. The FDA has referred to it as unapproved or unlabeled use: 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. Such 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. U.S. Food & Drug Admin., FDA Drug Bulletin, 12 FDA Drug Bull. 1, 5 (1982). 2 Available at Free Speech Amarin and First Amendment Challenges Baird et al. 13

14 Some physician groups, like the American Academy of Orthopaedic Surgeons, refer to the practice as physician-directed use to get more clearly at the idea that once a medical device or drug is lawfully on the market, physicians determine how to use those devices for a particular patient using their own knowledge, training, experience and judgment, and that FDA labeling does not constrain a physician s discretion in how to provide that medical care. See, e.g., American Academy of Orthopedic Surgeons, FDA Regulatory Status And Informed Consent 3 ( The FDA regulates the marketing and sale of drugs and medical devices in the United States, including requiring that the label of a drug or medical device list specific information. Any use not expressly listed on the label constitutes physician-directed or off-label use; such use is legal, acceptable, and in many instances, a relatively common practice among clinicians. ). Along these same lines, evidence-based regimen gets at the idea that physicians usage decisions are fundamentally grounded in data and information. See Cline v. Oklahoma Coalition for Reproductive Justice, 313 P.3d 253, 258 (Okla. 2013) ( The practice of providing approved medications using regimens different from that described in the medication s final printed label is known as an off-label use, or an evidence-based regimen. The FDA has stated that evidence-based regimens are common, permissible, and can be required by good medical practice. ). Off-label use not only is accepted and expected under the regulatory scheme, but it also is a common feature of the practice of medicine. See Randall S. Stafford, Regulating Off-Label Drug Use: Rethinking the Role of the FDA, 358 N. Engl. J. Med. 1427, 1427 (2008) (providing that a comprehensive study conducted in 2001 found that approximately 21% of all prescriptions are for offlabel purposes). In some circumstances, an off-label use may well constitute the standard of care required for physicians. See U.S. Food & Drug Admin., Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs & Medical Devices (Dec. 2011) (stating that off-label use may even constitute a medically recognized standard of care ); see also Memorandum of the AMA House of Delegates, Resolution 820, Off- Label Use of Pharmaceuticals (Sept. 21, 2005) (providing that [u]p to date, clinically appropriate medical practice at times requires the use of pharmaceuticals for off-label indications ). Limiting what device and drug manufacturers can say about off-label uses even as the regulatory scheme and medical practice permit or even encourage those uses creates tension: [P]rohibiting off-label promotion by a pharmaceutical manufacturer while simultaneously allowing off-label use paternalistically interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public s detriment, informed and intelligent treatment decisions. Caronia, 703 F.3d at Available at Drug and Medical Device May 2016

15 At times, the FDA itself recognizes that the public health can be served when health care professionals receive truthful and non-misleading scientific and medical information on unapproved uses of approved or cleared medical products. Riley v. Cordis Corp., 625 F. Supp. 2d 769, 782 n.7 (D. Minn. 2009). After all: Cline, 313 P.3d at 258. [H]uman progress is not static: medical research and advances do not stop upon a particular drug s approval by the FDA. Researchers continue to perform clinical trials, doctors continue to gain experience, and widespread use of a particular treatment allows the medical community to collect data about side effects, alternative doses, and potential new uses for treatments. Moreover, promotion of off-label uses is not inherently untruthful or misleading. See In re Actimmune Mktg. Litig., 614 F. Supp. 2d 1037, 1051, n.6 (N.D. Cal. 2009), aff d 464 Fed. Appx. 651 (9th Cir. 2011) ( [O]ff-label marketing of an approved drug is itself not inherently fraudulent. ); In re Epogen & Aranesp Off-Label Mktg. & Sales Practices Litig., 590 F. Supp. 2d 1282, (C.D. Cal. 2008) (for fraud, not enough for plaintiff to allege mere off-label promotion; plaintiff must also establish that the statements were literally false, misleading, or omitted material facts). B. Federal Law Does Not Expressly Prohibit Off-Label Promotion, But FDA Views It As Adulteration Or Misbranding While there is clarity about the permissibility of off-label use of medical device and drugs, there is less clarity about federal limitations on off-label promotion. See, e.g., Raab v. Smith & Nephew, Inc., F. Supp. 3d, 2015 WL , at *16 (S.D.W.Va. Dec. 15, 2015) ( [T]here has been some dispute over the extent to which federal law actually prohibits a manufacturer s promotion that is not false and misleading but that nonetheless fails to comply with federal regulatory requirements. ); Schouest v. Medtronic, Inc., 13 F. Supp. 3d 692, 702 (S.D. Tex. 2014) (describing the legal underpinning of the supposed ban on offlabel promotion as not clear ). Nowhere in the FDCA or FDA regulations or guidelines is there any express prohibition of off-label promotion, or speech by manufacturers about offlabel uses of their devices and drugs. See Caronia, 703 F.3d at There is authority stating otherwise, but such statements usually are made in passing and without examination of the underlying federal statutes, regulations, Free Speech Amarin and First Amendment Challenges Baird et al. 15

16 Instead, the FDCA explicitly prohibits misbranding meaning the introduction or delivery for introduction into interstate commerce of any food, drug, device, tobacco product, or cosmetic that is adulterated or misbranded. 21 U.S.C. 331(a). 5 While there are other ways in which a drug or device can be misbranded [see 21 U.S.C. 352(a)-(n)], of relevance here is that a drug or device can be deemed misbranded is if its labeling does not bear adequate directions for use. 21 U.S.C. 352(f). The FDA defines adequate directions for use in terms of directions which allow a drug to be used safely and for the purposes for which it is intended. 21 C.F.R ; see also 21 CFR (d) (similar, for devices). In turn, the intended use refers to the objective intent of the persons legally responsible for the labeling of drugs, which is determined by such persons expressions or may be shown by the circumstances surrounding the distribution of the article. 21 C.F.R ; 21 C.F.R (similar, for devices). Objective intent may be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives. 21 CFR ; see also 21 C.F.R (devices). It may 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. 21 C.F.R ; see also 21 C.F.R In September 2015, FDA proposed a revision to 21 C.F.R , to provide that the term intended uses : [R]efer[s] to the objective intent of the persons legally responsible for the labeling of drugs. The intent is determined by such persons expressions or may be shown by the circumstances surrounding the distribution of the article. This objective intent may, for example, be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives. It may be and guidance documents. See, e.g., Coleman, 223 Cal. App. 4th at 423 (citing the general prohibition on misbranding, 21 U.S.C. 331(a) as support for the remark that FDA regulations prohibit a device manufacturer from promoting the use of a device in a manner inconsistent with premarket approval ); Alton v. Medtronic, Inc., 2013 WL , *22 (D. Or. Sept. 6, 2013) (criticizing Ramirez v. Medtronic, Inc., 2013 WL (D. Ariz. Aug. 21, 2013) for asserting that off-label promotion directly violates the FDCA). 5 Misbranding can result in criminal prosecution. See 21 U.S.C. 333(a)(2) (providing that if any person commits such a violation... such person shall be imprisoned for not more than three years or fined not more than $10,000, or both. ) Drug and Medical Device May 2016

17 shown, for example, by circumstances in which 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. The intended uses of an article may change after it has been introduced into interstate commerce by its manufacturer. If, for example, a packer, distributor, or seller intends an article for different uses than those intended by the person from whom he received the drug, such packer, distributor, or seller is required to supply adequate labeling with the new intended uses. Amendments to Regulations Regarding Intended Uses, 80 Fed. Reg. 186 (Sept. 25, 2015). A similar change was proposed to 21 C.F.R , which defines intended use as it applies to medical devices. Id. To date, however, no final rule has been published. The FDA thus has at times taken the position that an approved drug that is marketed for an unapproved use (whether in labeling or not) is misbranded because the labeling of such drug does not include adequate directions for use. See U.S. Food & Drug Admin., Draft Guidance, Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific References Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices, 2-3 (2009). C. FDA Nevertheless Permits Certain Speech By Manufacturers About Off-Label Uses Although the foregoing reflects FDA s general position to date, it has issued guidance documents reflecting its view that certain forms of speech by manufacturers about off-label uses are permissible (or not promotional), namely certain independent and non-promotional industry-supported activities that facilitate the free exchange of data and views in the scientific community, and distributing scientific reprints in certain circumstances. 6 With regard to industry-supported scientific and educational activities, FDA considers a number of factors in assessing whether a given conference or program involving off-label discussions are independent and non-promotional. See U.S. Food & Drug. Admin, Guidance for Industry: Industry-Supported Scientific And Educational Activities (1997). Factors include control over the program content, meaningful disclosures, the business relationships between the conference organizer and the manufacturer, the opportunity for meaningful 6 In addition to FDA regulations, voluntary industry guidelines also provide recommendations about acceptable practices on these topics, such as the AdvaMed Code of Ethics, available at Free Speech Amarin and First Amendment Challenges Baird et al. 17

18 discussion, accreditation, and documentation of the conference organizer s independence. Id. In addition, FDA issued a draft guidance in 2011 regarding how manufacturers should handle inquiries about off-label uses of a drug or device, such as an inquiry from the audience made during a live presentation. See U.S. Food & Drug Admin., Draft Guidance for Industry: Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs & Medical Devices (Dec. 2011); U.S. Food & Drug Admin., Truthful Prescription Drug Advertising and Promotion. 7 Under this draft guidance, if an individual makes a public unsolicited request for off-label information, the manufacturer is to only provide contact information for its office of medical affairs, and is not to provide any off-label information, even if it is truthful and not misleading. Id. With regard to the distribution of scientific reprints, FDA updated its guidance in February See U.S. Food & Drug Admin., Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses Recommended Practices (February 2014) 8 ; see also U.S. Food & Drug Admin., Draft Guidance, 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, 3 (2009). In the 2014 draft guidance, the FDA explains that when a manufacturer distributes journal articles that include information on off-label uses of its drug, the FDA will not use the fact of such distribution as evidence of the manufacturer s intent that the drug be used for an unapproved use, provided that the manufacturer makes certain disclosures with the articles. Amarin Pharma, Inc., et al v. United States Food & Drug Admin., et al., 119 F. Supp. 3d 196, (S.D.N.Y. 2015). If, however, a sales representative characterizes a journal article to suggest that a certain drug or device is safe or effective for an unapproved use, the agency may use that speech as evidence that the manufacturer intended to promote that use. Id. at 209. For example, a journal article that is distributed by a manufacturer that is about an unapproved use shall not be marked, highlighted, summarized or characterized by the manufacturer, in writing or orally, to emphasize or promote an unapproved use For example, if during a sales call to a physician, 7 Available at nce/drugmarketingadvertisingandcommunications/ucm htm. 8 Available at guidances/ucm pdf Drug and Medical Device May 2016

19 a sales representative summarizes or characterizes the article to emphasize portions that suggest the manufacturer s [product] may be safe or effective for an unapproved use, this might be used as evidence of intended use. U.S. Food & Drug Admin., Draft Guidance for Industry: Distributing Scientific and Medical Publications on Unapproved New Uses Recommended Practices (February 2014). In court filings, the government has made somewhat different acknowledgements. For example, in proposed jury instructions filed in U.S.A. v. Vascular Solutions, Inc., et al., No. 5:14-cr (W.D. Tex.) (filed Aug. 13, 2015), the Department of Justice acknowledged that it is not a crime for a device company or its representatives to give doctors wholly truthful and non-misleading information about the unapproved use of a device. And in an appellate brief filed in Caronia, the government acknowledged that [p]romoting an approved drug for off-label uses is not itself a prohibited act under the FDCA, nor is it an element of any prohibited act. Brief of United States, United States v. Caronia, Nos , , 2010 WL , at *51 (2d Cir., filed Oct. 8, 2010). Whether these FDA admissions in legal briefing will translate into future regulations remains to be seen. On December 14, 2015, Janet Woodcock, M.D., the Director for the FDA s Center for Drug Evaluation and Research, spoke at the FDA/CMS Summit on CDER 2016 Priorities. Listed as a Front Burner Priority was the FDA s need to [r]e-evaluate our regulation of drug advertising and promotion in light of current jurisprudence around the 1st Amendment: ongoing, progress made, but more work needed. How long this planned rulemaking will take remains to be seen, but given the complexity of the issues, the process could take months or years Free Speech Amarin and First Amendment Challenges Baird et al. 19

20 II. The First Amendment Framework: Commercial Speech Basics Few would doubt that common forms of promotion are speech within the meaning of the First Amendment, whether print or broadcast advertisements or a dialogue between people or entities about a device or drug. 9 The creation and dissemination of information are speech within the meaning of the First Amendment and [s]peech in aid of pharmaceutical marketing... is a form of expression protected by the Free Speech clause of the First Amendment. Sorrell v. IMS Health Inc., 131 S. Ct. 2653, 2667 (2011) (emphasis added). A. Commercial And Non-Commercial Speech That there may be a commercial purpose to speech does not take it outside of the First Amendment. Commercial speech traditionally has been defined as speech related solely to the economic interests of the speaker and its audience [Central Hudson Gas & Elec. Corp. v. Pub. Serv. Comm n of N.Y., 447 U.S. 557, 561 (1980)] or speech that proposes no more than a commercial transaction [Bolger v. Youngs Drug Prods. Corp., 463 U.S. 60, 66 (1983)]. The Supreme Court has, however, recognized a distinction between commercial speech and other types of speech for purposes of determining how closely courts must scrutinize the nature, purpose, and effect of any governmental restrictions placed on it. See Central Hudson Gas & Elec. Corp. v. Pub. Serv. Comm n of N.Y., 447 U.S. 557, 561 (1980). While the First Amendment protects commercial speech from unwarranted governmental regulation, it traditionally has been far more protective of other types of speech. Id. at 561. In particular, where noncommercial speech is at issue, content-based speech restrictions are subject to strict judicial scrutiny. Content-based laws those that target speech based on its communicative content are presumptively unconstitutional and may be justified only if the government proves that they are narrowly tailored to serve compelling state interests. Reed v. Town of Gilbert, 135 S. Ct. 2218, 2226 (2015), citing R.A.V. v. St. Paul, 505 U.S. 377, 395 (1992). In addition, the First Amendment provides unique protections for scientific speech. 10 See Miller v. California, 413 U.S. 15, 23 (1973) ( scientific 9 The federal government, however, does at times argue that given promotional activities are evidence of conduct, not speech. See United States v. Vascular Solutions, No. 14-cr-926 (W.D. Tex. Jan. 27, 2016) (order denying criminal defendant s motion to exclude evidence of truthful, non-misleading speech, relying on Department of Justice s representation that the evidence reflected conduct, not speech). 10 Scientific speech is defined as speech that implicates a scientific proposition, with implication including (1) a truth-value for that proposition ( true, false, or uncertain ) and (2) a justification for that truth-value. C. P Drug and Medical Device May 2016

21 expression is one of the categories of speech recognized as fully protected by the First Amendment); see also Gertz v. Robert Welch, Inc., 418 U.S. 323, 339 (1974) ( Under the First Amendment there is no such thing as a false idea. ); American School of Magnetic Healing v. McAnnulty, 187 U.S. 94, 106 (1902) (postmaster may not decide that one side of medical controversy, such as the benefits of smallpox vaccination or homeopathy, is fraudulent ); United States v. Harkonen, 2009 WL , at *6 (N.D. Cal. June 4, 2009) ( speech is protected by the First Amendment if it is a bona fide scientific and educational speech that appears in independent and peer-reviewed sources, such as a journal article reprint or a medical textbook. ); Wallach v. Crawford, 2005 WL , at *8 n.11 (S.D. Cal. Mar. 29, 2005) ( [t]he First Amendment protects scientific speech and expression ); Metabolife International, Inc. v. Wornick, 72 F. Supp. 2d 1160, 1172 (S.D. Cal. 1999) ( the safety of [the product] remains an open question of substantial public importance, contributions to the debate are protected by the First Amendment ), aff'd in pertinent part, rev'd in part, 264 F.3d 832 (9th Cir. 2001). Even if Plaintiff had evidence that the article authors has some financial motivation, that would not affect the full scope of the First Amendment protection afforded to the speech contained in those scientific publications. See Neurotron, Inc. v. American Ass'n of Electrodiagnostic Medicine, 189 F. Supp. 2d 271, 277 (D. Md. 2001) ( even if there is some commercial aspect of the article, it would not be considered commercial speech... because of its public significance and status as an academic piece published by a non-profit organization. ) aff d, 48 Fed. App x. 42 (4th Cir. 2002) (for the reasons stated in the opinion below); see also Riley v. Nat l Federation of the Blind, Inc., 487 U.S. 781, 796 (1988); ONY Corp. v. Cornerstone Therapeutics, Inc., 720 F.3d 490 (2d Cir. 2013); Bracco Diagnostics, Inc. v. Amersham Health, Inc., 627 F. Supp. 2d 384, 456 (D.N.J. 2009). 11 First Amendment free speech jurisprudence continues to evolve, however. Commentators have noted that the Supreme Court s First Amendment jurisprudence is increasingly intolerant of government restrictions on speech, whatever the form of the restriction or the type of speech. See, e.g., E. Zaret, Commercial Speech and the Evolution of the First Amendment, Washington Lawyer (September 2015). As this First Amendment evolution continues, FDA Guzelian, Scientific Speech, 93 Iowa L. Rev. 881, 906 (2008) (footnote omitted). 11 Scientific controversies must be settled by the methods of science rather than by the methods of litigation. [citation omitted]. More papers, more discussion, better data, and more satisfactory models not larger awards of damages mark the path toward superior understanding of the world around us. Underwager v. Salter, 22 F.3d 730, 736 (7th Cir. 1994) (suit between authors of competing books). In McMillan v. Togus Regional Office, 294 F. Supp. 2d 305, 316 (E.D.N.Y. 2003), the court dismissed, on First Amendment grounds, a suit against scientific entities engaged in scientific and engineering research for conducting allegedly invalid research into Agent Orange. Id. at 306. The court rejected the suit as an attempt to litigate the validity of scientific studies. Id. at Free Speech Amarin and First Amendment Challenges Baird et al. 21

22 restrictions on off-label promotion increasingly are ripe for reconsideration of whether they pass constitutional muster. B. Traditional Intermediate Scrutiny For Government Restrictions On Commercial Speech In Central Hudson, the Supreme Court affirmed what it termed the commonsense distinction between speech proposing a commercial transaction, which occurs in an area traditionally subject to government regulation, and other varieties of speech. Central Hudson, 447 U.S. at 562 (internal quotations omitted). Although there is a distinction between commercial and non-commercial speech, commercial speech still receives constitutional protection so long as it is not misleading and concerns lawful activity. Under the intermediate scrutiny test recognized in Central Hudson, commercial speech that is not misleading and that concerns lawful activity can be constitutionally regulated by the government only if (1) the government interest in regulating the speech is substantial, and justifies the regulation; (2) the regulation directly advances the governmental interest asserted; and (3) the regulation is narrowly drawn and may not be more extensive than necessary in order to serve the interest. Id. at 566. The threshold Central Hudson criterion asking whether the speech is not misleading and not concerning unlawful activity is a key one, because there can be no constitutional objection to the suppression of commercial messages that do not accurately inform the public about lawful activity. The government may ban forms of communication more likely to deceive the public than to inform it. Id. at 563. Assuming the commercial speech is truthful and concerning lawful activity, however, courts do examine the governmental purpose and the nature of the restriction in question with some rigor under this test. In Central Hudson itself, for example, the Court overturned a local government rule that prohibited all advertising that promot[es] the use of electricity but permitted other forms of advertising about electricity usage, such as ads seeking to shift demand from periods of peak electricity usage to off-peak times. Id. at C. Heightened Scrutiny Applies To Content-Based Government Restrictions On Commercial Speech The Supreme Court returned to First Amendment protections for commercial speech in Sorrell v. IMS Health Inc., 131 S. Ct (2011), a case involving a Vermont statute restricting the distribution of pharmacy records about the prescribing practices of individual doctors. Under the Vermont statute, such records could be sold to private or academic researchers, but could not be sold to data mining companies that would use the information for pharmaceutical marketing. Id. at Drug and Medical Device May 2016

23 Writing for the majority and overturning the First Circuit s contrary conclusion, Justice Kennedy observed that this restriction was content-based, because an individual who engaged in educational communications could purchase the information, but those who intended to use the information for marketing were barred from doing so. Id. In fact, the restriction was also speaker-based, because the statute disfavor[ed] specific speakers, namely pharmaceutical manufacturers while permitting others. Id. As the Court explained, the First Amendment requires heightened scrutiny whenever the government creates a regulation of speech because of disagreement with the message it conveys. Id. at 2664 (quoting Ward v. Rock Against Racism, 491 U.S. 781, 791 (1989)). Because the Vermont statute was content-based and picked a particular viewpoint for disfavored treatment, the statute would be invalidated regardless of whether a special commercial speech inquiry or a stricter form of judicial scrutiny was applied, and regardless of whether the statute burdened only commercial speech or other speech as well. Id. at Nevertheless, the Court held that [u]nder a commercial speech inquiry, it is the State s burden to justify its content-based law as consistent with the First Amendment. Id. In order to satisfy this burden, the State must show at least that the statute directly advances a substantial governmental interest and that the measure is drawn to achieve that interest. Id., at Although Vermont asserted two justifications for its statute protecting medical privacy and physicians who find detailing harassing, and improving health while decreasing costs the Court held that the statute did not directly further either of those. Id., at In addition, the Court observed that the fear that people would make bad decisions if given truthful information does not justify content-based burdens on speech, and the statute impermissibly burdened a form of protected expression that it found too persuasive while simultaneously left unburdened those speakers whose messages are in accord with its own views. Id. at As the Supreme Court noted, [t]he more benign, and many would say, beneficial speech of pharmaceutical marketing is also entitled to the protection of the First Amendment. If pharmaceutical marketing affects treatment decisions, it does so because doctors find it persuasive... the fear that speech might persuade provides no lawful basis for quieting it. Sorrell v. IMS Health, 131 S. Ct. 2653, 2670 (2011) (citing Brandenburg v. Ohio, 395 U.S. 444, 447 (1969)). D. Topic-Based Government Restrictions Are Content-Based Restrictions Last year, in Reed v. Town of Gilbert, 135 S. Ct (2015), the Supreme Court returned to the issue of content-based restrictions on speech and the level of scrutiny that such restrictions require Free Speech Amarin and First Amendment Challenges Baird et al. 23

24 Reed involved a town sign ordinance that allowed the outdoor display of some types of signs without a permit, but imposed restrictions on the number, placement, and time for sign displayed depending on the subject matter of the sign at issue. Reed, 135 S. Ct. at The code defined types of signs, such as ideological or political or a temporary directional signs indicating the location of an event being held by a non-profit (like church services), and the display restrictions varied depending on the type of content. In evaluating whether the sign ordinance at issue was content-based, the Court reiterated that such laws are presumptively unconstitutional and subject to strict scrutiny. Id. at It then spent some time examining what exactly is meant by content-based restrictions. The Reed Court first cited Sorrell for the proposition that [g]overnment regulation of speech is content based if a law applies to particular speech because of the topic discussed or message expressed. Id. at 2226 (citing Sorrell, 131 S. Ct. at ). It also noted that restrictions can be content-based on their face, or nominally content-neutral. Some facial distinctions based on a message are obvious, defining regulated speech by particular subject matter, and others are more subtle, defining regulated speech by its function or purpose. Id. at Facially-neutral laws nevertheless are content-based if they cannot be justified without reference to the content of the regulated speech, or that were adopted by the government because of disagreement with the message conveyed. Id. (internal quotations and citations omitted). In Reed, the code, on its face, was content-based. Id. For example, certain standards applied only if the sign directed the public to a church or other qualifying event. Id. Strict scrutiny thus applied, but the government could not establish that the code s distinctions between types of signs furthered a compelling government interest and was narrowly tailored to that purpose. Id. at Those asserted interests were in preserving town aesthetics and traffic safety but, even after the Court assumed those were valid purposes, it had little trouble concluding the ordinance was hopelessly underinclusive and thus not sufficiently tailored to the asserted need. Id. at E. Are Government Restrictions On Off-Label Promotion Topic- Based, And Which Standard Applies? Reed reflects yet another step forward in recent development of the Supreme Court s approach to content-based government restrictions on speech. The Court s declaration that the restrictions at issue in that case were contentbased is significant because at least for non-commercial speech a contentbased finding triggers the presumptive unconstitutionality standard and aggressive strict scrutiny review. While it remains to be seen whether Reed s content-based approach will have precedential effect in the context of commercial speech, Reed s reliance on Drug and Medical Device May 2016

25 Sorrell itself a commercial speech case to define what is content-based signals that the Court itself may not think that the commercial speech/non-commercial speech divide is that meaningful when it comes to content-based restrictions. The Supreme Court s decision in Reed thus may be potentially significant for drug and device manufacturers. The FDA s regulation of speech regarding off-label use is topic-based in that speech is prohibited if it is on one topic (offlabel uses) but permitted if on another (on-label uses). In fact, the FDA s regulation is also speaker-based because anyone other than a manufacturer is free to make truthful and non-misleading statements about a product s off-label uses, but those same statements by the manufacturer may result in an FDA enforcement action. The trend in these cases certainly points away from using the Central Hudson s intermediate scrutiny test to evaluate the FDA s restrictions on truthful, non-misleading speech about off-label use of pharmaceutical products or medical devices. Combining Reed s explanation about the nature of content-based speech with the heightened scrutiny that Sorrell applied when the content-based speech was commercial speech should result in courts reviewing off-label promotion restrictions in a more rigorous manner. Moreover, where speech about product uses and risks fits into the scientific speech paradigm discussed above in Section II.A, that is another pathway through which strict scrutiny may apply Free Speech Amarin and First Amendment Challenges Baird et al. 25

26 III. Recent Cases Involving The First Amendment And Government Restrictions On Truthful, Non-Misleading Off-Label Promotion Even as we await further clarification from the Supreme Court about First Amendment free speech issues, the lower courts continue to confront and decide such issues in the off-label promotion context. A. Caronia v. United States, 703 F.3d 149 (2d. Cir. 2012): The First Amendment As A Shield Against Criminal Misbranding Charges The decision of Caronia v. United States, 703 F.3d 149 (2d Cir. 2012) is important for our discussion because it reflects the use of First Amendment as a shield by an individual charged with criminal misbranding. The Court in Caronia held that the First Amendment prevents the government from prosecuting an individual under 21 U.S.C. 331(a) and 333(a)(2) for off-label promotional speech, without more. 1. Factual Background The product at issue in Caronia was a drug called Xyrem, originally manufactured by Orphan Medical, Inc. and later acquired by Jazz Pharmaceuticals. Caronia, at 703 F.3d at 155. The FDA approved Xyrem for two different indications: (1) to treat narcolepsy patients who experience a condition called cataplexy, a condition associated with weak muscles, and (2) to treat narcolepsy patients with excessive daytime sleepiness. Id. Xyrem s active ingredient is gamma-hydroxybutryate ( GHB ), which some refer to as the date rape drug. Id. The FDA required a black box warning accompany the drug in order to guard against Xyrem s potentially serious side-effects, including difficulty breathing while sleeping, confusion, depression, nausea, and vomiting. Id. The labeling also advised that the drug s safety and efficacy were not established in patients under 16 years of age, and the drug had very limited experience among elderly patients. Id. Alfred Caronia was hired by Orphan in March 2005 as a Specialty Sales Consultant to promote Xyrem. Id. at He started the company s speaker programs for the drug, which enlisted physicians, for pay, to speak to other physicians about FDA-approved drug use. Id., at 156. Under the company s procedures, if Caronia, or any other sales consultant, was asked about the off-label uses of the drug, he was not permitted to answer. Id. One of the physicians Caronia hired for this program was Dr. Peter Gleason. Id. In the spring of 2005, the federal government launched an investigation into Orphan s off-label promotion practices. During the investigation, Caronia was recorded speaking with Dr. Gleason about uses of Xyrem, including unapproved indications and unapproved subpopulations. Id. Caronia reportedly indicated that the drug could be used for muscle disorders and chronic pain (the Drug and Medical Device May 2016