Compounding Animal Drugs from Bulk Ingredients: Not Prohibited by Federal Food Drug and Cosmetic Act

Not Prohibited by Federal Food Drug and Cosmetic Act

June 28, 2013

The Federal Food Drug & Cosmetic Act (FD&CA) gives FDA broad, wide and far-reaching regulatory powers. Prohibiting the compounding of medicines from bulk ingredients, however, is not one of them. The position that the FD&CA prohibits pharmacists from compounding animal drugs from bulk ingredients is simply incorrect.

A federal district court, the only court to review the issue, explicitly rejected the position that the FD&CA prohibits pharmacists from compounding animal drugs from bulk ingredients:

The undisputed evidence … shows that allowing the FDA to enjoin a pharmacist’s traditional, state-authorized practice of bulk compounding of animal drugs could destabilize the pharmacy profession and leave many animal patients without necessary medication. Such a result would be especially troublesome because the FDA’s longstanding policy has been to permit, and even promote, pharmacists’ compounding from bulk ingredients. The FDA cannot simply upset the expectations it helped to create through decades of inaction without explanation, especially where it asserted expansion of authority impacts the federal-state balance and potentially subjects many individuals and companies to criminal liability.

United States v. Franck’s Lab, Inc., et al. (816 F. Supp. 2d 1209 (M.D. Fl. 2011) (emphasis added))

The FDA’s Historical Regulation and Enforcement of Compounding with Bulk Substances Further Questions the Implied FD&CA Prohibition

1938 For approximately the first 50 years after the enactment of the FD&CA in 1938, the FDA generally left regulation of compounding to the states.
1988 United States v. 9/1 Kg. Containers (854 F.2d 173 (7thCir. 1988)) held that bulk ingredients suppliers could not sell to veterinarians except for specific circumstances. The case did not mention selling to pharmacists and courts have distinguished 9/1 Kg. Containers as being inapplicable to pharmacists.
1989 United States v. Algon Chemical, Inc., (879 F.2d 1154 (3rdCir. 1989)) held that bulk ingredients suppliers could not sell to veterinarians except for specific circumstances. The case did not mention selling to pharmacists and courts have distinguished Algon Chemical, Inc. as being inapplicable to pharmacists.
1992 The 1992 Compliance Policy Guide listed nine noninclusive activities that the FDA believed improperly crossed the line between “pharmacist” and “manufacturer.” Compounding drugs from bulk substances was not among the nine prohibited practices.
1994 Animal Medicinal Drug Use Clarification Act (AMDUCA) – The FDA regulations promulgated to implement AMDUCA. The regulations did not purport to regulate the practice of compounding and instead point to the FDA’s nonbinding guidance documents regarding compounding. Further, the regulations distinguish between nonfood-producing animals and food-producing animals. With regard to nonfood-producing animals, the regulations state: “[b]ecause extralabel use of animal and human drugs in nonfood-producing animals … does not ordinarily pose a threat to the public health, extralabel use of animal and human drugs is permitted in nonfood-producing animal practice except when the public health is threatened.”
1996 The 1996 Compliance Policy Guide listed 13 situations that would likely indicate compounding subject to regulatory action. Compounding from bulk drug substances for use in nonfood animals was expressly identified as a “compounding situation [which] would not ordinarily be considered a regulatory action.” Compounding from bulk drugs for use in food animals, however, was one of the listed scenarios. The FDA noted in the Guide that there was “occasionally a need to utilize … bulk drug substances for compounding into an appropriate dosage form.” The FDA would thus condone compounding animal drugs from bulk where (1) a legitimate medical need was identified; (2) there was “a need for an appropriate dosage regimen” for the patient’s species; and (3) there was “no marketed approved animal drug” that “may treat the condition diagnosed in the available dosage form.” The FDA asserted in the Guide that “two Federal Appeals Court decisions, Algon and 9/1 kg. Containers, affirmed the FDA position that the FD&CA does not permit veterinarians to compound unapproved finished drug products from bulk drugs unless the finished drug is not a new animal drug. The principle established by the court applies equally to compounding by pharmacists.” Notably, the FDA similarly asserted in the Guide that compounding a new animal drug from “an approved … human or animal drug” would result in a violation of the FD&CA, but acknowledged that this would no longer be the case when the AMDUCA became effective.
1997 The Food and Drug Modernization Act of 1997 (FDAMA) authorized pharmacists to compound drug products “using bulk drug substances” so long as the bulk drugs comply with the applicable USP monograph or if no monograph exists, the bulk drugs are components of drugs approved by the FDA.
2000 In FDA v. Brown & Williamson (529 U.S. 120 (2000)), the Supreme Court found that in certain circumstances, a literal reading of a broadly drawn public health statute (specifically, the FD&CA) should be rejected when it encompasses conduct that exceeds the original congressional intent. The Court declared that “Congress could not have intended to delegate a decision of such economic and political significance to an agency in so cryptic a fashion” and the Court found that the FDA’s claim to jurisdiction contravened the clear intent of Congress.
2002 In Thompson v. Western States (535 U.S. 357 (2002)), the Supreme Court noted the importance of compounding and agreed with the government’s position that because obtaining FDA approval for a new drug is a costly process, it would as a practical matter “eliminate the practice of compounding and thereby eliminate availability of compounded drugs for those patients who have no alternative treatment.” Although the Supreme Court invalidated the advertising provisions of the FDAMA, the Court found that “it would not make sense to require compounded drugs created to meet the unique needs of individual patients to undergo the testing required for the new drug approval process.” Furthermore, the Supreme Court expressly acknowledged the historical importance of traditional pharmacy compounding and openly questioned whether Congress could have intended to subject compounded drugs to the FD&CA’s new drug approval process.
2002 The 2002 Compliance Policy Guide addresses human drugs, but allows use of compounding from bulk for human drugs so long as the bulk ingredients are FDA-approved.
2003 The 2003 Compliance Policy Guide addresses animal drugs. FDA did not publish the Guide in Federal Register or invite public comment. More than 70 members of Congress wrote separately to the FDA reiterating policy concerns of the 2003 Guide regarding compounding from bulk substances. While the 2002 Guide permits compounding of human drugs from bulk substances under certain circumstances, the practice was entirely prohibited for animals, except for nine listed exceptions, by the 2003 Guide. Further, while the 1996 Guide acknowledges the occasional utility of compounding from bulk, this was absent in the 2003 Guide. Note the disparate treatment of human and animal compounding: Under the 2002 and 2003 Guides, “a pharmacist who compounds medication from bulk for ingestion by a horse is … subject to an FDA enforcement action, while the same pharmacist compounding medication from bulk for ingestion by the human rider of that horse is not.”
2004 FDA issued notice of revising the 2003 Guide but has never taken action to revise it. In 2005, 26 senators and 72 congressmen reiterated their displeasure over the agency’s failure to revise the 2003 Guide and subject it to notice and comment procedures.
2007 A FDA Center for Veterinary Medicine (CVM) update from May 2007 regarding concerns about supplies of pergolide for horses noted CVM’s efforts included trying to make the approved product available through veterinary distribution channels and exercising enforcement discretion as appropriate over the pharmacy compounding of pergolide. Bulk substance used for pharmacy compounding should be labeled for “animal use only.” All pharmacy compounding must be done under a “valid veterinary prescription.”
2008 In Medical Ctr. Pharm. v. Mukasey, 536 F.3d 383, 2008 U.S. App. LEXIS 15276 (5th Cir. Tex. 2008), the court, citing Algon and 9/1 Kg. Containers as additional support, held that compounded drugs are new animal drugs under the FD&CA, and unless the compounded drugs are exempt under the FD&CA’s AMDUCA provisions, compounded drugs are subject to FD&CA’s unsafe, adulteration and misbranding requirements. As with human drugs, the FD&CA contains no blanket “implicit exemption” for animal drugs produced by compounding.
2011 The court in Franck’s Lab distinguished Algon and 9/1 Kg. Containers. The court noted that neither case mentioned pharmacists or the practice of pharmacy. Algon and 9/1 Kg. Containers also predated a number of important legal developments relating to both the FDA’s regulation of compounding and the Chevron doctrine. The court held that in enacting the FD&CA in 1938, Congress did not intend to give the FDA per se authority to enjoin the longstanding, widespread, state-regulated practice of pharmacists’ filling a veterinarian’s prescription for a nonfood-producing animal by compounding from bulk substances. The 11th Circuit vacated and rendered moot the District Court opinion on a procedural ground because the company went out of business during the appeals process.