United States v. Regenerative Sciences, LLC
408 U.S. App. D.C. 259
| D.C. Cir. | 2014Background
- Appellants (Drs. Centeno and Schultz, Michelle Cheever, and Regenerative Sciences, LLC) developed and offered the "Cultured Regenexx Procedure," which cultures a patient’s mesenchymal stem cells (MSCs) and mixes them with doxycycline before reinjection into the same patient (an autologous therapy).
- FDA sued seeking a permanent injunction, alleging the Mixture is a drug and biological product that is adulterated (violating cGMP) and misbranded (labeling defects) under the FDCA and PHSA; district court granted summary judgment to the government and entered a permanent injunction.
- Key factual concessions: appellants culture MSCs to change growth/biological characteristics, sometimes add differentiation agents, and add doxycycline obtained via interstate commerce; appellants’ labels lack required "Rx only" marking and adequate directions for use.
- Appellants argued the Mixture is an unregulated medical procedure, not a drug/biologic; that federal regulation intrudes on state medical-practice authority and exceeds Commerce Clause limits; and that exemptions (HCT/P minimal-manipulation under 21 C.F.R. pt.1271 and compounding under 21 U.S.C. §353a) apply.
- Court held the Mixture qualifies as a drug and biological product; use of an interstate ingredient (doxycycline) suffices to meet §331(k)’s interstate commerce requirement; Part 1271 minimal-manipulation exemption did not apply on the record; the mixture violated cGMP and labeling rules; permanent injunction affirmed.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether the Mixture is a "drug" or "biological product" subject to FDCA/PHSA | Government: Mixture is intended to treat orthopedic disease and affect body function, so falls within statutory definitions | Appellants: Procedure is medical practice/autologous treatment not subject to federal drug/biologic regulation | Held: Mixture is a drug and biological product; statutory definitions apply despite autologous context |
| Commerce Clause / §331(k) "shipment in interstate commerce" requirement | Government: use of doxycycline (interstate) brings product within §331(k) | Appellants: Entire Mixture produced and used intrastate; single ingredient cannot satisfy shipment requirement | Held: Use of an ingredient shipped interstate satisfies §331(k); federal commerce power applies (Raich/Wickard) |
| Applicability of 21 C.F.R. §1271 minimal-manipulation exemption for HCT/Ps | Appellants: culturing here is minimal manipulation; exemption shields them from FDCA manufacturing/labeling requirements | Government: culturing and added agents alter relevant biological characteristics; exemption inapplicable | Held: Exemption not established by appellants; conceded culturing alters characteristics so exemption fails |
| Compounding exemption under 21 U.S.C. §353a | Appellants: cultured MSCs are components of FDA-approved Carticel, so qualify as bulk drug substances | Government: appellants produced no evidence MSCs are represented for use in Carticel or other approved drugs | Held: Appellants failed to show MSCs are "bulk drug substance" as required; compounding exemption fails |
| Adulteration (cGMP) claim | Government: appellants’ manufacturing methods/facilities violated cGMP (21 C.F.R. pts.210–211) so product is adulterated per se | Appellants: relied on their own safety protocols and practice suspension during litigation | Held: Undisputed cGMP violations make Mixture per se adulterated; appellants’ conduct supports conclusion |
| Misbranding / labeling (adequate directions, "Rx only") | Government: labels omit "Rx only" and adequate directions for prescription drug; misbranding results | Appellants: product made for their own patients so labeling rules shouldn't apply as to directions | Held: Mixture is a prescription drug; lacks required label information and "Rx only"; misbranded; Evers distinguished and not controlling |
| Permanent injunction standard | Government: likelihood of future violations based on repeated inspections, uncorrected violations, and business opportunities | Appellants: ceased Procedure during litigation, adopted safety protocols; injunction unnecessary | Held: District court adequately found pattern/flagrant violations and risk of recurrence; injunction affirmed |
Key Cases Cited
- Gonzales v. Raich, 545 U.S. 1 (2005) (federal regulation may reach purely local activities that are part of an economic class substantially affecting interstate commerce)
- Wickard v. Filburn, 317 U.S. 111 (1942) (aggregation principle supports federal regulation of local production impacting interstate markets)
- United States v. Sullivan, 332 U.S. 689 (1948) (interstate commerce in drugs continues after initial intrastate sale)
- United States v. Evers, 643 F.2d 1043 (5th Cir. 1981) (distinguishable holding concerning physician prescribing and advertising of FDA-approved drugs)
- United States v. Dianovin Pharm., Inc., 475 F.2d 100 (1st Cir. 1973) (use of components shipped interstate brings activities within §331(k))
- John D. Copanos & Sons, Inc. v. FDA, 854 F.2d 510 (D.C. Cir. 1988) (drugs produced in violation of manufacturing regulations are per se adulterated)
- United States v. Philip Morris USA Inc., 566 F.3d 1095 (D.C. Cir. 2009) (standard for permanent injunction: reasonable likelihood of future violations and factors to consider)