Since 2002, the law governing pharmacy compounding (21 USC 353a) has suffered a crippling constitutional defect. It took a significant human tragedy to draw the attention of Congress, and on September 27, 2013, the House and Senate announced agreement on the Drug Quality and Security Act. Under Title I the "Compounding Quality Act" seeks to amend the Food Drug and Cosmetic Act ("FDCA") by inserting a new section, 21 USC 353b. According to House Member Waxman "[t]he bill will correct the constitutional defect in the FDA's drug compounding statute that has wreaked havoc on the Agency's ability to effectively enforce the law for years." (See here).
The "constitutional defect" relates to the "advertising and promotion" provisions having been declared unconstitutional in Thompson v. Western States, 535 US 357 (2002). Confusion concerning the status of the law was compounded because the Supreme Court did not rule on whether the unconstitutional provision was severable. In the Ninth Circuit, the entire Pharmacy Compounding provision had been stricken, but the Fifth Circuit took a different view in Medical Center Pharmacy v. Mukasey, 536 F.3d 383 (5th Cir. 2008) ruling the advertising prohibitions were severable.
Pharmacy compounding of medications predates the Food Drug and Cosmetic Act (FDCA") and is as old as the practice of medicine itself. In 2012, Massachusetts based New England Compounding Center ("NECC") was at the center of a meningitis outbreak linked to contaminated sterile injections that were ultimately linked to multiple deaths. Even though the federal law had been in a state of disarray for more than a decade, the NECC disaster could have been avoided by simply following up on the warning signals that had been plainly obvious and for which the State of Massachusetts and the FDA had ample authority and power.
On November 15, 2012, after hearing emotional testimony from the family of a patient who had been exposed to a NECC product, a sanctimonious Congress raked an evasive and nonresponsive Food and Drug Administration ("FDA") Commissioner Hamburg over the coals for failing to coherently explain the FDA's authority to regulate and oversee the practice of compounding pharmacy generally and for failing to follow up on its 2002 warnings to NECC. (See here).
In its July 31, 2013 report to Congress, the Government Accountability Office recommended that Congress close the "gap" in FDA oversight caused by "compounding in large drugs quantities - in anticipation of individual prescriptions or without prescriptions" where the drugs are sold across state lines rendering the practice drug manufacturing that should be overseen by FDA." (See GAO report here)
Pharmacy compounding has largely been considered an adjunct to the practice of medicine and not pharmaceutical manufacturing. The practice does not fit neatly within the FDA's current statutory or regulatory purview and has traditionally been reserved for the states. Long before the NECC debacle, the proliferation of large scale compounding facilities increased, and the FDA sought a regulatory framework requiring larger compounding pharmacies to register and list what they are compounding. The FDA presupposed that large scale compounding was in need of FDA oversight.
Congress has not agreed to rewrite the entire law or to supplant state oversight of pharmacy practice; instead, it seeks to revive the former "pharmacy compounding" provisions in section 353a by deleting the prohibition against soliciting prescriptions in subsection (a) and deleting the "advertising and promotion" provision in subsection (c) in their entirety. As for large scale traditional compounding pharmacies the proposed Compounding Quality Act returns to 2002 imposing the limitations for "inordinate amounts" and "5%" under 353a(b)(3)(B)(i-ii).
Something New – Outsourcing Facilities:
In earlier versions of the Bill, Congress echoed the concerns of the FDA and was concerned with the notion of large scale Compound Manufacturing - where pharmacies compound drugs in large quantities in anticipation of individual prescriptions or without prescriptions. The agreed version of the new Compounding Quality Act abandons the notion of "Compound Manufacturing" in favor of regulating a discrete class of "outsourcing facilities" defined as:
The term 'outsourcing facility' means a facility at one geographic location or address that—(i) is engaged in the compounding of sterile drugs;(ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section.(B) An outsourcing facility is not required to be a licensed pharmacy. (C) An outsourcing facility may or may not obtain prescriptions for identified individual patients.
The election is a Hobson's choice where not "electing" to be an outsourcing facility will subject the facility producing sterile preparations to the rules on misbranding and new drugs. An outsourcing facility is required to register annually, pay a $15,000 registration fee (unless if they have under $1M in sales, in which case they pay $5,000) and must report to the FDA in June and December of each year, identifying the drugs compounded. The FDA will conduct what are termed "risk-based" inspections under 21 USC 374. These inspections are the same as those for traditional drug manufacturers. The registration fee or "establishment fee" covers the cost of an inspection but the fee for each successive reinspection is $15,000.
The new law also subjects outsourcing facilities to the records retention and adverse event reporting requirements under Subpart D of the regulations (21 CFR 310.305) as traditional drug manufacturers. The failure to comply with the reporting requirements is considered a "prohibited act" which is subject to civil and criminal penalties. 21 USC 331.
Congress did take one important step by amending the drug misbranding provisions under 21 USC 353 to include compounded drugs. Borrowing from the rules governing approved drugs, a compounded drug is misbranded under the FDCA:
if the advertising or promotion of a compounded drug is false or misleading in any particular.
The new Compounding Quality Act will pave the way for increased use of the FDA's 2002 Compounding Policy Guide (CPG) for oversight of the promotion of pharmacy compounding products for both sterile and other compounded products. CPG Sec. 140.100 addresses the circumstances under which the FDA will seize books and other materials that constitute misleading labeling and states:
Printed material that promotes the use of a product is labeling within the meaning of the Act. Notwithstanding certain free speech protections, labeling including books can be regulated if it is false or misleading.
The controversy over the pharmacy compounding provisions stemmed from the Supreme Court ruling in Western States. Congress purports to cure the First Amendment constitutional infirmity by simply erasing it. The problem with this approach is that it provides the FDA no road-map on how to regulate communications or product labeling. In enforcing the FDCA, the FDA assumes that there is a fundamental distinction under the First Amendment between truthful information and information the government declares "false," which is not entitled to protection. While the terms "false" and "misleading" are generally defined in the regulations (21 CFR 202.1), the FDA subscribes to the view of Justice Roberts in Jacobellis v. Ohio, 378 U.S. 184 (1964) that "it knows it when it sees it." Zauderer v. Office of Disciplinary Counsel 471 U.S. 626, 646 (1985) is often cited by the government to support the notion that "false" speech is not afforded First Amendment protection. However, in U.S. v. Alvarez, 132 S. Ct. 2537 (2012), the Supreme Court rejected this notion stating that it "has never endorsed the categorical rule the Government advances: that false statements receive no First Amendment protection." The notion that the government urges that "false" speech is not subject to First Amendment protection has only recently been rejected by the Supreme Court.
Since the advent of the FDCA in 1906, the government could rely on Court's generally deferring to administrative determinations and, where the government declared a statement, label or advertisement to be false, it could proceed to enforcement without concern for Due Process or the First Amendment. But deference to agency determinations is also being reconsidered by the Court. For example, in Christopher v. Smithkline Beecham Corp., the Supreme Court refused to defer to an agency's interpretation of ambiguous regulations, stating:
It is one thing to expect regulated parties to conform their conduct to an agency's interpretations once the agency announces them; it is quite another to require regulated parties to divine the agency's interpretations in advance or else be held liable when the agency announces its interpretations for the first time in an enforcement proceeding and demands deference.
In FCC v. Fox Television Stations, Inc., the Supreme Court considered the issue of deference to regulatory agencies in the context of the First Amendment holding that the regulation failed under the Due Process Clause, because "regulated parties should know what is required of them so they may act accordingly;" and "precision and guidance are necessary so that those enforcing the law do not act in an arbitrary and discriminatory way."
There is little doubt that the proposed Compounding Quality Act will provide the FDA with significant oversight over sterile compounding facilities, and will provide the FDA, state regulators and consumers with increased transparency on the scope of "unapproved" compounded sterile preparations on the market. Congress has directed the FDA to issue regulations (not Guidance) governing pharmacy compounding but no deadline was set for publication of a proposed rule. How the FDA will reign in the burgeoning business of non-sterile compounding will need to await the rulemaking process.