United States v. Regenerative Scis., LLC

• Decision Date: 04 February 2014
• Docket Number: No. 12–5254.,12–5254.
• Citation: 741 F.3d 1314
• Parties: UNITED STATES of America, Appellee v. REGENERATIVE SCIENCES, LLC, A Corporation, et al., Appellants.
• Court: U.S. Court of Appeals — District of Columbia Circuit

741 F.3d 1314

UNITED STATES of America, Appellee

v.REGENERATIVE SCIENCES, LLC, A Corporation, et al., Appellants.

No. 12–5254.

United States Court of Appeals, District of Columbia Circuit.

Argued Oct. 21, 2013.

Decided Feb. 4, 2014.

Appeal from the United States District Court for the District of Columbia (No. 1:10–cv–01327).

Andrew S. Ittleman argued the cause for appellants. With him on the briefs was Mitchell S. Fuerst.

Jonathan W. Emord was on the brief for amicus curiae American Association of Orthopaedic Medicine in support of appellants.

Lawrence J. Joseph was on the brief for amicus curiae Association of American Physicians and Surgeons, Inc., in support of appellants.

James S. Turner was on the brief for amicus curiae Tim Moore in support of appellants.

Abby C. Wright, Attorney, U.S. Department of Justice, argued the cause for appellee. With her on the brief were Stuart F. Delery, Principal Deputy Assistant Attorney General, Ronald C. Machen, Jr., U.S. Attorney, Mark B. Stern, Attorney, William B. Shultz, Acting General Counsel, Food and Drug Administration, and Eric M. Blumberg, Deputy Chief Counsel. Alisa B. Klein, Attorney, U.S. Department of Justice, entered an appearance.

Before: GRIFFITH and SRINIVASAN, Circuit Judges, and EDWARDS, Senior Circuit Judge.

Opinion for the court filed by Circuit Judge GRIFFITH.

GRIFFITH, Circuit Judge:

In this civil enforcement action, we must decide whether the appellants—three individuals and a related corporate entity—violated federal laws regulating the manufacture and labeling of drugs and biological products by producing, as part of their medical practice, a substance consisting of a mixture of a patient's stem cells and the antibiotic doxycycline. Because we conclude that they did, we affirm the district court's judgment and the permanent injunction it entered against appellants.

I

A

This case involves two statutes under which the Food and Drug Administration (FDA) regulates the healthcare industry: the Federal Food, Drug & Cosmetic Act (FDCA), 21 U.S.C. § 301 et seq., and the Public Health Service Act (PHSA), 42 U.S.C. § 201 et seq. Those statutes promote the safety of drugs and biological products, respectively, by setting forth detailed requirements for how such substances are to be manufactured and labeled. See21 U.S.C. §§ 351 (FDCA manufacturing requirements), 352 (FDCA labeling requirements); 42 U.S.C. § 262(j) (incorporating by reference most of the FDCA's provisions, including its manufacturing and labeling requirements, into the PHSA). Drugs and biological products not satisfying those requirements are deemed “adulterated” or “misbranded,” see21 U.S.C. §§ 351, 352, 353(b)(4); 42 U.S.C. § 262(j), and doing any act that causes a drug or biological product to be adulterated or misbranded is a violation of federal law, 21 U.S.C. § 331(k); 42 U.S.C. § 262(j). The FDA may seek an injunction to prohibit such violations. 21 U.S.C. § 332(a); 42 U.S.C. § 262(j).

B

The substance at issue in this case is produced by appellants Dr. Christopher Centeno, Dr. John Schultz, Michelle Cheever, and Regenerative Sciences, LLC, as part of a medical therapy that they market as the “Cultured Regenexx Procedure” (the Procedure). Drs. Centeno and Schultz, who practice medicine together at the Centeno–Schultz Clinic in Colorado, jointly developed the Procedure to treat patients' orthopedic conditions. They are the majority shareholders of Regenerative Sciences, which they founded and which, in turn, owns the Procedure and licenses it exclusively to the Centeno–Schultz Clinic. Michelle Cheever is the laboratory director for Regenerative Sciences.

The Procedure begins with the extraction of a sample of a patient's bone marrow or synovial fluid. From that sample, Regenerative Sciences isolates mesenchymal stem cells (MSCs), which are capable of differentiating into bone and cartilage cells. The MSCs are then placed in a solution to culture them—that is, to cause them to divide and proliferate. Other substances are sometimes added to the solution that affect the MSCs' differentiation. The culturing process determines the growth and biological characteristics of the resulting cell population. When the MSCs are sufficiently numerous for re-injection, they are combined with doxycycline, an antibiotic obtained in interstate commerce and used to prevent bacterial contamination of the MSCs. The resulting mixture (the Mixture) is injected into the patient from whom the stem cell sample was initially taken, at the site of the damaged tissue.

Appellants promote the Procedure as an alternative to surgery for various orthopedic conditions and diseases. In court filings, they have described the Procedure as a “treatment [for] orthopedic injuries and arthritis” and for “musculoskeletal and spinal injury.” Their promotional materials recommend the Procedure for treatment of osteoarthritis, non-healing bone fractures, chronic bulging lumbar discs, and soft tissue injuries.

In August 2010, the government filed this action for a permanent injunction against appellants, alleging that the Mixture is both a drug and a biological product that is adulterated and misbranded in violation of § 331(k) of the FDCA and § 262(j) of the PHSA, which incorporates § 331(k) by reference. Appellants counterclaimed, asserting that the Mixture is not subject to federal regulation and that, even if it is, the FDA's effort to regulate the Mixture is defective under both the PHSA and the Administrative Procedure Act (APA), 5 U.S.C. § 706(2).

The district court granted the government's motion for summary judgment and dismissed appellants' counterclaims, holding that they had violated the FDCA and the PHSA. United States v. Regenerative Scis., LLC, 878 F.Supp.2d 248, 263 (D.D.C.2012). Then, finding a “cognizable danger of a recurrent violation,” the district court entered a permanent injunction prohibiting appellants from committing further violations of the FDCA's adulteration and misbranding restrictions. Id. at 262–63 (internal quotation marks omitted). Appellants timely appealed both orders.

We have jurisdiction to review the district court's orders under 28 U.S.C. § 1291. We review the grant of summary judgment and dismissal of appellants' counterclaims de novo, “drawing all reasonable inferences from the evidence in the light most favorable to the nonmoving party,” Geleta v. Gray, 645 F.3d 408, 410 (D.C.Cir.2011), and affirming only if “there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law,” Fed.R.Civ.P. 56(a). We review the district court's entry of a permanent injunction for abuse of discretion and its factual findings for clear error. United States v. Philip Morris USA Inc., 566 F.3d 1095, 1110 (D.C.Cir.2009) (per curiam).

II

Appellants' principal argument is that the Mixture is not subject to regulation under the FDCA or PHSA because it is neither a drug nor a biological product but is, rather, a medical procedure. The text of those statutes forecloses this argument.

The FDCA defines a “drug” as any “article[ ] intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” or “intended to affect the structure or any function of the body.” 21 U.S.C. § 321(g)(1); see also21 C.F.R. § 201.128 (providing that a drug's intended use is shown by “the objective intent of the persons legally responsible for the labeling of [the] drug[ ],” which “may ... be shown by labeling claims, advertising matter, or oral or written statements by such persons or their representatives”). The PHSA defines “biological product” in similarly broad terms as any “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative ... or analogous product ... applicable to the prevention, treatment, or cure of a disease or condition of human beings.” 42 U.S.C. § 262(i)(1). Both of these wide-ranging definitions clearly apply to the Mixture, an article derived mainly from human tissue and intended to treat orthopedic diseases and to affect musculoskeletal function. Indeed, appellants do not actually dispute that the plain language of the statutes compels this conclusion.

Rather, appellants urge us to construe the FDCA in light of purported federalism concerns.¹ But appellants' concerns lack merit. They boil down to the following syllogism: the FDCA was not intended to infringe on states' traditional role in regulating the practice of medicine; the Procedure fits Colorado's statutory definition of the “practice of medicine”; therefore, the FDA's regulation of the Procedure exceeds the FDA's authority under the FDCA. This syllogism is flawed twice over.

First, it misapprehends what this case is about. Notwithstanding appellants' attempt to characterize this case as an effort by the FDA to “restrict[ ] the use of an autologous stem cell procedure,” ² Appellants' Br. 8 (emphasis added), the focus of the FDA's regulation is the Mixture. That is, the FDA does not claim that the procedures used to administer the Mixture are unsafe; it claims that the Mixture itself is unsafe. Appellants' arguments about the practice-of-medicine exemption are therefore wide of the mark.

Second, appellants are wrong to suggest that the scope of the FDCA depends on state-by-state definitions of the “practice of medicine.” The FDCA enacts a comprehensive, uniform regulatory scheme for the distribution of drugs. The scheme's breadth—and, more specifically, its applicability to doctors—is evident in the fact that the FDCA carves out certain exceptions from its requirements for doctors who manufacture and administer drugs in the course of their professional practice. See, e.g.,21 U.S.C. § 360(g)(2) (exempting licensed healthcare practitioners engaged in certain activities from the FDCA's registration requirements); id. § 374(a)(2)(B) (narrowing the FDA's ability to review the records of licensed healthcare practitioners “who manufacture, prepare, propagate,...