Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 1 of 21
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF COLUMBIA
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`Civil Action No. 22-1702
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`OUTSOURCING FACILITIES
`ASSOCIATION
`1050 Connecticut Ave., NW
`Suite 1100
`Washington, D.C. 20036-5403,
`
`Plaintiff,
`
`v.
`
`XAVIER BECERRA
`in his official capacity as
`Secretary of Health and Human Services
`200 Independence Avenue, SW
`Washington, DC 20201,
`
`U.S. DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`200 Independence Avenue, SW
`Washington, DC 20201,
`
`ROBERT M. CALIFF
`in his official capacity as
`Commissioner of Food and Drugs
`10903 New Hampshire Avenue
`Silver Spring, MD 20993, and
`
`U.S. FOOD AND DRUG
`ADMINISTRATION
`10903 New Hampshire Avenue
`Silver Spring, MD 20993,
`
`Defendants.
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`

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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 2 of 21
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`COMPLAINT FOR DECLARATORY AND INJUNCTIVE RELIEF
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`Plaintiff Outsourcing Facilities Association (“OFA”) brings this complaint against
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`Defendants Xavier Becerra, Robert Califf, U.S. Department of Health and Human Services
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`(“HHS”), and U.S. Food and Drug Administration (“FDA”) (collectively, “Defendants”) for
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`violating the Administrative Procedure Act (“APA”). In support thereof, OFA states the
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`following:
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`NATURE OF ACTION
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`1.
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`This action challenges as a violation of the Administrative Procedure Act
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`Defendants’ unreasonable delay in carrying out Congress’s directive to list the bulk drug
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`substances (i.e., active pharmaceutical ingredients) “for which there is a clinical need.” 21 U.S.C.
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`§ 353b(a)(2)(A)(i). Congress assigned this task to the HHS Secretary nearly a decade ago. Yet,
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`Defendants still have not listed a single bulk drug substance for compounding sterile drugs.
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`2.
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`In November 2013, Congress quickly reacted to an urgent crisis in the nation’s
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`supply of safely compounded sterile drugs by creating a new type of FDA-regulated entity called
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`“the drug compounding outsourcing facility.” These facilities are also known as “503B facilities”
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`because they were created by Section 503B of the Food, Drug, and Cosmetic Act (“FD&C Act”)
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`to safely compound sterile drugs. Plaintiff Outsourcing Facilities Association (“OFA”) is a trade
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`association whose members responded to Congress’s urgent call by making substantial
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`investments to establish 503B facilities and register them with the U.S. Food and Drug
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`Administration (“FDA”).
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`3.
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`Congress intended 503B facilities to supply safely compounded sterile drugs to
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`the nation’s healthcare providers using bulk drug substances for which there is a clinical need
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`and directed the HHS Secretary to list those substances in the Federal Register using 60-day
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 3 of 21
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`notice and comment procedures. 21 U.S.C. § 353b(a)(2)(A)(i). The Secretary delegated that
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`responsibility to FDA, which refers to the list as the “503B Bulks List.”
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`4.
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`In more than eight years, however, FDA has added only four substances to the
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`503B Bulks List, all of which are for compounding topical dosage forms, not sterile drugs.
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`Defendants’ unreasonable delay in identifying the bulk drug substances for which there is a
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`clinical need is thwarting Congress’ purpose in creating 503B facilities and hurting public health
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`by denying healthcare providers’ access to the safely compounded sterile drugs their patients
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`need.
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`5.
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`In 2018, FDA established a process to publicly categorize nominations for adding
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`a bulk drug substance to the 503B Bulks List. The categorization of nominations is how FDA
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`indicates whether the nominator provided sufficient information for FDA to act on the
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`nomination or if the nominator must supply more information. FDA stated at the time that it
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`would categorize nominated substances monthly. Yet, FDA has not categorized many of the
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`nominations it has received, including more than 30 of the OFA-nominated substances. More
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`than half of those OFA-nominated substances were submitted to FDA more than three years ago.
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`6.
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`Defendants should comply with Congress’s directive to list the bulk drug
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`substances for which there is a clinical need so the facilities Congress created to compound
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`sterile drugs for the nation’s healthcare providers can serve public health as Congress intended.
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`At a minimum, FDA should follow its own policy by promptly categorizing the nominations that
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`have languished in regulatory limbo for years and categorize any new nominations monthly as it
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`said it would.
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 4 of 21
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`PARTIES
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`7.
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`Plaintiff Outsourcing Facilities Association is the trade association representing
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`FDA-registered outsourcing facilities (“503B facilities”) operating pursuant to Section 503B of
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`the FD&C Act. OFA’s members provide compounding services to patients, healthcare providers,
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`and healthcare facilities, and strive to ensure the specific needs of both providers and patients are
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`met with safe and effective compounded and/or repackaged medications. OFA has been actively
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`following FDA’s implementation of the Compounding Quality Act (“CQA”) and has brought
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`together members of industry to advocate for a safe, reasonable and practical rollout of the CQA.
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`OFA’s offices are located at 1050 Connecticut Ave., NW Suite 1100, Washington, D.C. 20036-
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`5403.
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`8.
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`Defendant Xavier Becerra (“Secretary”) is Secretary of U.S. Health and Human
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`Services (“HHS”). He maintains offices at 200 Independence Avenue, SW, Washington, D.C.
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`20201. In his capacity as Secretary, he is responsible for the conduct and policies of HHS.
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`Defendant Becerra, by and through his designees at HHS, has delayed and withheld the agency
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`action Congress required. His governmental activities occur in this District and nationwide.
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`Defendant Becerra is sued solely in his official capacity.
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`9.
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`Defendant Robert Califf (“Commissioner”) is Commissioner of the U.S. Food and
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`Drug Administration (“FDA”). FDA is the agency that administers the programs under the
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`Federal Food, Drug, and Cosmetic Act (“FD&C Act”). Defendant Califf, by and through his
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`designees at FDA, has delayed and withheld the agency action Congress required. His
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`governmental activities occur in this District and nationwide. Defendant Califf is sued solely in
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`his official capacity.
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 5 of 21
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`10.
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`Defendant HHS is a cabinet-level department of the United States government. Its
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`headquarters and principal place of business are at 200 Independence Avenue, SW, Washington,
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`D.C. 20201. Its governmental activities occur in this District and nationwide.
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`11.
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`Defendant FDA is an agency of the United States and a division of HHS. FDA’s
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`headquarters and principal place of business are at 10903 New Hampshire Avenue, Silver
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`Spring, MD 20993. Its governmental activities occur in this District and nationwide. FDA is the
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`federal agency in charge of administering the FD&C Act, including implementation of the Drug
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`Quality and Security Act of 2013 (“DQSA”).
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`JURISDICTION AND VENUE
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`12.
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`This Court has subject matter jurisdiction over this action pursuant to 28 U.S.C. §
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`1331 because this action presents a case and controversy under the Federal Food, Drug, and
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`Cosmetic Act, 21 U.S.C. § 301 et seq. (“FD&C Act”) and the Administrative Procedure Act, 5
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`U.S.C. § 551 et seq. (“APA”).
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`13.
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`Plaintiff’s claims for declaratory and injunctive relief are authorized by 28 U.S.C.
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`§§ 2201 and 2202, 5 U.S.C. § 706, 28 U.S.C. § 1361, 28 U.S.C. § 1651(a), Rules 57 and 65 of
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`the Federal Rules of Civil Procedure, and the general legal and equitable powers of this Court
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`(which exist even absent a finding of unreasonable delay).
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`14.
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`OFA has standing because it, and at least one of its members, have been and
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`continue to be harmed by Defendants’ delay in identifying the bulk drug substances “for which
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`there is a clinical need,” as required under 21 U.S.C. § 353b(a)(2)(A)(i). These injuries would be
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`redressed by requiring Defendants to fulfil their obligation to identify those bulk drug
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`substances. Through this lawsuit, OFA seeks to vindicate interests that are germane to its
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`purposes. Litigation will not be adversely affected by the absence of the individual members of
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 6 of 21
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`OFA as named parties in this lawsuit. Consistent with its purpose as a trade association whose
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`members are outsourcing facilities registered under Section 503B of FD&C Act, OFA, as well as
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`its members, nominated substances that FDA should identify as bulk drug substances for which
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`there is a clinical need. OFA has expended and continues to expend resources because of
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`Defendants’ unlawful delay in identifying the bulk drug substances for which there is a clinical
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`need. OFA submitted a citizen petition to FDA under 21 C.F.R. § 10.30, dated September 30,
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`2020, requesting, among other things, that FDA establish the list of bulk drug substances for
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`which there is a clinical need within the next 180 days. FDA denied the petition on January 25,
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`2021. One or more of OFA’s members would compound sterile drugs pursuant to Section 503B
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`using the nominated substances if FDA identified them as substances for which there is a clinical
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`need.
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`15.
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`Venue lies in this district under 28 U.S.C. § 1391(e) in that Defendants Becerra
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`and Califf are officers and employees of a United States agency, Defendants reside in the District
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`of Columbia, a substantial part of the events giving rise to this claim occurred in the District of
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`Columbia, Plaintiff resides in this district, and no real property is involved in the action. Venue
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`also lies in this district under 5 U.S.C. § 703 because there is no special statutory procedure for
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`appeal and this court is a court of competent jurisdiction.
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`STATUTORY AND REGULATORY BACKGROUND
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`A.
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`Congress created Section 503B outsourcing facilities to compound sterile
`drug products for the nation’s healthcare providers.
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`16.
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`In November 2013, Congress created a new category of regulated entity—drug
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`compounding outsourcing facilities—by adding Section 503B to the FD&C Act. Compounding
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`Quality Act (“CQA”) (Title I of the Drug Quality and Security Act (“DQSA”)), Pub. L. No. 113-
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`54, 127 Stat. 587 (2013).
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 7 of 21
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`17.
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`A drug compounding “outsourcing facility”—also known as a 503B facility—is
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`defined in Section 503B of the FD&C Act as “a facility at one geographic location or address
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`that (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an
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`outsourcing facility; (iii) and complies with all of the requirements of this section.” 21 U.S.C. §
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`353b(d)(4). A “sterile drug” is one “intended for parenteral administration, an ophthalmic or oral
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`inhalation drug in aqueous format, or a drug that is required to be sterile under Federal or State
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`law.” 21 U.S.C. § 353b(d)(5). Compounding is the act of “combining, admixing, mixing,
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`diluting, pooling, reconstituting, or otherwise altering of a drug or bulk drug substance to create a
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`drug.” 21 U.S.C. § 353b(d)(1).
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`18.
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`Congress enacted the DQSA—creating 503B facilities—to remedy the legacy of
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`unregulated and unsafe compounding practices for sterile drugs, culminating in a 2012 outbreak
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`of fungal meningitis that killed more than 60 people and infected 750 others when the New
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`England Compounding Center (NECC)—which was not a 503B facility—compounded
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`purportedly sterile drugs that were tainted with bacterial and fungal contamination. Congress
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`immediately held hearings to determine how to ensure healthcare providers would have a safe
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`supply of compounded sterile drugs so that another NECC-type tragedy would not recur. See
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`Hearing on the Fungal Meningitis Outbreak: Could It Have Been Prevented? 112th Cong. (Nov.
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`14, 2012). Congress reacted with urgency to find a legislative solution. See 159 Cong. Rec.
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`14,650 (2013) (statement of Rep. Murphy) (“How we got here is a tragedy.”); S. Hrg. No. 113-
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`756, at 22 (statement of Sen. Baldwin) (“Last year’s tragic meningitis outbreak underscored the
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`importance of updating Federal compounding policy.”); 159 Cong. Rec. 14,647 (2013)
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`(statement of Rep. Pitts) (explaining Congress sought to “prevent against another tragedy like
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`NECC’s”); H. Ser. No. 113-31, at 7 (statement of Rep. Upton) (“We have to do something that is
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`truly effective to prevent this from happening again.”); id. at 9 (statement of Rep. Waxman)
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`(“Our most critical task is to answer this question: how can we prevent another NECC tragedy
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`from occurring again?”).
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`19.
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`At the same time, Congress recognized that “[w]ithout compounders, doctors
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`would not perform surgeries. Without compounders, oncologists would be forced to administer
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`alternative chemotherapy drugs. Without compounders, patients would suffer from limited
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`access.” 159 Cong. Rec. S8071-04 (daily ed. Nov. 18, 2013) (statement of Sen. Boozman).
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`Recognizing the urgent need for healthcare providers to have a safe supply of compounded
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`sterile drugs, Congress expeditiously passed the DQSA, paving the way for compounding of
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`sterile drugs from bulk drug substances to be carried out by newly created entities—503B
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`facilities—that are held to the most stringent federal standards for compounding sterile drugs.
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`20.
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`To ensure that healthcare providers have access to safe, compounded drugs,
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`Congress intended 503B facilities to compound sterile drugs for hospitals, clinics, and healthcare
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`practitioners to keep on hand as “office stock” for patients who present with an immediate need
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`for them. 503B facilities provide their compounded sterile drugs directly to the healthcare
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`providers that need them as drugs compounded by 503B facilities cannot be sold or transferred
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`by an entity other than the FDA-registered facility that compounded them. 21 U.S.C. §§
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`353b(a)(8). Other compounders, such as state-licensed pharmacies (sometimes referred to as
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`“traditional compounders”), compound drugs solely based on the receipt of a prescription for an
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`identified, individual patient. 21 U.S.C. § 353a.
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`21.
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`503B facilities are FDA-registered and FDA-inspected. 21 U.S.C. §§ 353b(b)(1),
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`353b(b)(4). The bulk drug substances they use to compound drugs are each manufactured by
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 9 of 21
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`FDA-registered manufacturers. 21 U.S.C. § 353b(a)(2)(C). 503B facilities report both the drugs
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`they compound and adverse events to the FDA. 21 U.S.C. §§ 353b(b)(2), 353b(b)(5).
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`22.
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`503B facilities are subject to more regulatory requirements and compound sterile
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`drugs under more stringent conditions than traditional compounders, including being subject to
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`current good manufacturing practice (“CGMP”) requirements under section 501(a)(2)(B) of the
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`FD&C Act. 21 U.S.C. § 351(a)(2)(B).
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`23.
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`503B facilities compound sterile drugs using active pharmaceutical ingredients
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`from two different sources, either from a packaged, FDA-approved drug or from FDA-registered
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`manufacturers of active pharmaceutical ingredients. When a 503B facility compounds a drug
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`using active pharmaceutical ingredient sourced from an FDA-registered manufacturer of that
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`substance it is referred to as compounding from a “bulk drug substance.” 21 U.S.C. § 353b(a)(2).
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`24.
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`FDA defines “bulk drug substance” as follows: “Bulk drug substance, as
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`referenced in sections 503A(b)(1)(A) and 503B(a)(2) of the Federal Food, Drug, and Cosmetic
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`Act, means the same as ‘active pharmaceutical ingredient’ as defined in [21 C.F.R.] § 207.1(b).”
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`21 C.F.R. § 207.3. FDA defines the term “active pharmaceutical ingredient” as follows: “Active
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`pharmaceutical ingredient means any substance that is intended for incorporation into a finished
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`drug product and is intended to furnish pharmacological activity or other direct effect in the
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`diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any
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`function of the body. Active pharmaceutical ingredient does not include intermediates used in the
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`synthesis of the substance.” 21 C.F.R. § 207.1.
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`25.
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`Congress authorized 503B facilities to compound drug products using bulk drug
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`substances for which there is a “clinical need” and instructed the Secretary to establish the list
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`“identifying bulk drug substances for which there is a clinical need” by
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`(I) publishing a notice in the Federal Register proposing bulk drug substances to
`be included on the list, including the rationale for such a proposal;
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`(II) providing a period of not less than 60 calendar days for comment on the
`notice; and
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`(III) publishing a notice in the Federal Register designating bulk drug substances
`for inclusion on the list.
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`21 U.S.C. § 353b(a)(2)(A)(i).
`B.
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`In more than eight years since Congress directed HHS to list the bulk drug
`substances for which there is a clinical need, Defendants have yet to list a
`single bulk drug substance for compounding sterile drugs.
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`26.
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`On December 4, 2013, FDA opened a docket to solicit nominations of bulk drug
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`substances for the 503B Bulks List, with a deadline of March 4, 2014. FDA, Bulk Drug
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`Substances That May Be Used To Compound Drug Products in Accordance With Section 503B
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`of the Federal Food, Drug, and Cosmetic Act, Concerning Outsourcing Facilities; Request for
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`Nominations, 78 Fed. Reg. 72838 (Dec. 4, 2013). On July 2, 2014, FDA extended the deadline to
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`September 30, 2014. FDA, Bulk Drug Substances That May Be Used To Compound Drug
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`Products in Accordance With Section 503B of the Federal Food, Drug, and Cosmetic Act,
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`Concerning Outsourcing Facilities; Revised Request for Nominations, 79 Fed. Reg. 37750 (July
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`2, 2014). By the September 30, 2014 deadline, FDA received nominations for the list of bulk
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`drug substances for which there is a clinical need, yet did not make clinical need determinations
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`regarding any of them.
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`27. More than one year later, on October 27, 2015, FDA opened a new docket to
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`again solicit nominations for the 503B Bulks List, but this time did not set a deadline for
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`nominations. FDA, Bulk Drug Substances That Can Be Used To Compound Drug Products in
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`Accordance With Section 503B of the Federal Food, Drug, and Cosmetic Act; Establishment of a
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`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 11 of 21
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`Public Docket, 80 Fed. Reg. 65770 (Oct. 27, 2015). In response to the October 27, 2015 notice,
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`FDA again received nominations for the 503B Bulks List, including from OFA.
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`28.
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`FDA did not announce any clinical need determinations regarding any bulk drug
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`substances until 2019, when it published a notice stating it had found “no clinical need for an
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`outsourcing facility to compound using the bulk drug substances nicardipine hydrochloride and
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`vasopressin and, therefore, we are not including nicardipine hydrochloride and vasopressin on
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`the 503B Bulks List.” FDA, List of Bulk Drug Substances for Which There Is a Clinical Need
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`Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 84 Fed. Reg. 7383 (March 4,
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`2019).
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`29.
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`On January 27, 2022, FDA decided not to include eight bulk drug substances on
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`the 503B Bulks List. FDA, List of Bulk Drug Substances for Which There is a Clinical Need
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`Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 87 Fed. Reg. 4240 (Jan. 27,
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`2022) (diazepam, dipyridamole, dobutamine hydrochloride (HCl), dopamine HCl, edetate
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`calcium disodium, folic acid, glycopyrrolate, and sodium thiosulfate (except for topical
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`administration)).
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`30.
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`There are several other bulk drug substances that FDA has proposed not to
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`include on the 503B Bulks List. See FDA, List of Bulk Drug Substances for Which There is a
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`Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 84 Fed. Reg.
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`7383 (March 4, 2019) (1: bumetanide); FDA, List of Bulk Drug Substances for Which There is a
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`Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 84 Fed. Reg.
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`46014 (Sept. 3, 2019) (8: ephedrine sulfate, famotidine, hydralazine hydrochloride, methacholine
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`chloride, sodium bicarbonate, sodium tetradecyl sulfate, trypan blue, and vecuronium bromide);
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`FDA, List of Bulk Drug Substances for Which There is a Clinical Need Under Section 503B of
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`the Federal Food, Drug, and Cosmetic Act, 85 Fed. Reg. 46126 (July 31, 2020) (13: hydroxyzine
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`HCl, ketorolac tromethamine, labetalol HCl, mannitol, metoclopramide HCl, moxifloxacin HCl,
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`nalbuphine HCl, polidocanol, potassium acetate, procainamide HCl, sodium nitroprusside,
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`sodium thiosulfate, and verapamil HCl); FDA, List of Bulk Drug Substances for Which There is
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`a Clinical Need Under Section 503B of the Federal Food, Drug, and Cosmetic Act, 86 Fed. Reg.
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`15673 (Mar. 24, 2021) (4: bromfenac sodium, mitomycin-C, nepafenac, and hydroxychloroquine
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`sulfate).
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`31.
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`The DQSA does not require FDA to create a “no clinical need list” nor to propose
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`not to include a substance on the 503B Bulks List yet FDA has decided to take such action.
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`32.
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`FDA did not list any substance on the 503B Bulks List until 2022, when FDA
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`added four substances “for topical use only”: Diphenylcyclopropenone (nominated on September
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`30, 2014; FDA-2013-N-1524-1363), glycolic acid (nominated on November 9, 2017; FDA-
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`2015-N-3469-0035), squaric acid dibutyl ester (nominated on September 30, 2014; FDA-2013-
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`N-1524-1363), and trichloroacetic acid (nominated on April 13, 2018; FDA-2018-D-1067-0005).
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`FDA, List of Bulk Drug Substances for Which There is a Clinical Need Under Section 503B of
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`the Federal Food, Drug, and Cosmetic Act, 87 Fed. Reg. 4240 (January 27, 2022). FDA placed
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`these four substances on the 503B Bulks List only for compounding drugs that are “for topical
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`use only” and not for compounding sterile drugs. Id.
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`33.
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`FDA is capable of final action on a nomination for the 503B Bulks List in under
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`two years, as shown in the case of vasopressin. Vasopressin was nominated for the 503B Bulks
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`List on April 1, 2017 (see FDA-2015-N-3469-0012 and FDA-2015-N-3469-0023) and FDA
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`published its decision not to list the substance on March 4, 2019. FDA, List of Bulk Drug
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`Substances for Which There Is a Clinical Need Under Section 503B of the Federal Food, Drug,
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`and Cosmetic Act, 84 Fed. Reg. 7383 (March 4, 2019). That 23-month period included a 35-day
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`government shutdown.
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`34.
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`In the context of new drug applications, FDA makes decisions on complete
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`applications within 6 to 10 months. Making a clinical need determination based on a complete
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`nomination is less complex than deciding a new drug application. Indeed, FDA has summarized
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`its evaluation of bulk drug substances as involving only a few steps. FDA, Evaluation of Bulk
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`Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food,
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`Drug, and Cosmetic Act at 18 (March 2019), available at
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`https://www.fda.gov/media/121315/download. First, FDA considers “Is the nominated bulk drug
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`substance a component of an FDA-approved drug product?” Id. If it is not, then FDA considers
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`“(2) Do the following factors, taken together, weigh in favor of a finding that there is a clinical
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`need for outsourcing facilities to compound using the nominated bulk drug substance? (a) The
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`physical and chemical characterization of the substance; (b) Any safety issues raised by the use
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`of the substance in compounding; (c) The available evidence of effectiveness or lack of
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`effectiveness of a drug product compounded with the substance, if any such evidence exists; and
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`(d) Current and historical use of the substance in compounded drug products, including
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`information about the medical condition(s) that the substance has been used to treat and any
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`references in peer-reviewed medical literature.” Id. If, on the other hand, the nominated bulk
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`drug substance is a component of an FDA-approved drug product, then FDA considers two more
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`questions. “Is there a basis to conclude, for each FDA approved product that includes the
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`nominated bulk drug substance, that (i) an attribute of the FDA-approved drug product makes it
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`medically unsuitable to treat certain patients for the condition that FDA is evaluating, and (ii) the
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`drug product proposed to be compounded is intended to address that attribute?” Id. And “Is there
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`a basis to conclude that the drug product proposed to be compounded must be produced from a
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`bulk drug substance rather than from an FDA-approved drug product?” Id.
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`35.
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`“There is ‘no per se rule as to how long is too long’ to wait for agency action …
`
`but a reasonable time for agency action is typically counted in weeks or months, not years.” In re
`
`Am. Rivers & Idaho Rivers United, 372 F.3d 413, 419 (D.C. Cir. 2004) (internal citation
`
`omitted). Yet, despite hundreds of nominations of bulk drug substances for compounding sterile
`
`drugs for the 503B Bulks List, to date—more than eight years after Congress directed the HHS
`
`Secretary to identify the bulk drug substances for which there is a clinical need so that 503B
`
`facilities could compound sterile drugs and supply them to the nation’s health care providers—
`
`Defendants have not listed a single bulk drug substance for compounding sterile drugs on the
`
`503B Bulks List. FDA has failed to do so despite the fact Congress, recognizing the urgency,
`
`expeditiously enacted the DQSA and defined a 503B outsourcing facility as one that “is engaged
`
`in the compounding of sterile drugs.” 21 U.S.C. § 353b(d)(4).
`
`36.
`
`FDA’s eight-year-plus delay is harming public health and undermining the
`
`statutory scheme by frustrating Congress’s intent to give healthcare providers access to sterile
`
`drugs compounded using bulk drug substances at the type of facility Congress created for this
`
`purpose. Until FDA acts, healthcare providers are left to source such drugs from drug
`
`compounders who are not held to the same high standards as 503B facilities, or from 503B
`
`facilities who supply them at the mercy of FDA’s enforcement discretion.
`
`C.
`
`FDA has not followed its own policies and procedures for processing
`nominations for the 503B Bulks List, leaving nominations in regulatory
`limbo for years.
`
`37.
`
`FDA established a process to categorize nominations in three categories:
`
`503B Category 1 – Substances Nominated for the Bulks List Currently Under Evaluation:
`These substances may be eligible for inclusion on the 503B bulks list, were nominated
`
`14
`
`

`

`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 15 of 21
`
`with sufficient supporting information for FDA to evaluate them, and do not appear on
`any other list.
`
`503B Category 2 – Substances Nominated for the Bulks List That Raise Significant
`Safety Risks: These substances were nominated with sufficient supporting information to
`permit FDA to evaluate them and they may be eligible for inclusion on the 503B bulks
`list. However, FDA has identified significant safety risks relating to the use of these
`substances in compounding pending further evaluation, and therefore does not intend to
`adopt the policy described for the substances in category 1. If FDA adds a substance to
`Category 2, it will publish a public communication (e.g., a safety alert) describing the
`safety risks and will post the communication on FDA’s human drug compounding
`website advising that the substance has been added to Category 2 and is no longer
`eligible for the policies that apply to substances in Category 1.
`
`503B Category 3 – Substances Nominated for the Bulks List Without Adequate Support:
`These substances may be eligible for inclusion on the 503B bulks list, but were
`nominated with insufficient supporting information for FDA to evaluate them. These
`substances can be re-nominated with sufficient supporting information through a docket
`that FDA has established, as discussed below in section III.B.
`
`FDA, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of
`the Federal Food, Drug, and Cosmetic Act (January 2017) (“Interim Policy”), available at
`https://www.fda.gov/regulatory-information/search-fda-guidance-documents/interim-policy-
`compounding-using-bulk-drug-substances-under-section-503b-federal-food-drug-and.
`
`38.
`
`FDA stated in its Interim Policy that when a substance is nominated in response to
`
`the docket it opened on October 27, 2015, “FDA will determine whether the nomination is
`
`supported with sufficient information to allow FDA to evaluate it. After FDA makes that
`
`determination, the nominated substance will be placed in one of the three categories described in
`
`section II.B.2 above, and the categorization will be published on the FDA website.” Interim
`
`Policy at 9.
`
`39.
`
`FDA said it “generally expects to categorize bulk drug substances nominated to
`
`the October docket and to publish updated categories on its website on the first business day of
`
`each month.” Interim Policy at 9. In fact, FDA has not categorized many of the bulk drug
`
`substance that have been nominated for the 503B Bulks List. And FDA has not published
`
`updates categorizing nominated substances on a monthly basis.
`
`15
`
`

`

`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 16 of 21
`
`40.
`
`For example, OFA nominated the following 18 bulk drug substances more than
`
`three years ago which FDA has not categorized:
`
`Substance
`
`Iodoquinol
`
`Lidocaine
`
`Tetracaine
`
`Nomination
`ID
`FDA-2015-N-
`Testosterone
`3469-0084
`Enanthate
`Benzoyl peroxide FDA-2015-N-
`3469-0104
`FDA-2015-N-
`3469-0128
`FDA-2015-N-
`3469-0133
`FDA-2015-N-
`3469-0150
`FDA-2015-N-
`3469-0170
`FDA-2015-N-
`3469-0206
`FDA-2015-N-
`3469-0230
`
`Methadone
`hydrochloride
`Hydrogen
`peroxide
`Amiodarone
`Hydrochloride
`(HCl)
`Isoproterenol
`Hydrochloride
`Gatifloxacin
`
`Prednisolone
`sodium phosphate
`Levocarnitine
`
`Nicotinamide
`Adenine
`Dinucleotide
`Azithromycin
`
`Dorzolamide
`
`Latanoprost
`
`Loteprednol
`
`Timolol
`
`FDA-2015-N-
`3469-0234
`FDA-2015-N-
`3469-0255
`FDA-2015-N-
`3469-0274
`FDA-2015-N-
`3469-0278
`FDA-2015-N-
`3469-0281
`
`FDA-2015-N-
`3469-0284
`FDA-2015-N-
`3469-0287
`FDA-2015-N-
`3469-0288
`FDA-2015-N-
`3469-0289
`FDA-2015-N-
`3469-0290
`
`Regulations.gov URL
`
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0084
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0104
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0128
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0133
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0150
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0170
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0206
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0230
`
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0234
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0255
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0274
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0278
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0281
`
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0284
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0287
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0288
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0289
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0290
`
`Date FDA
`Received
`6/11/18
`
`7/23/18
`
`7/23/18
`
`7/23/18
`
`7/23/18
`
`8/17/18
`
`10/8/18
`
`10/31/18
`
`10/31/18
`
`3/4/19
`
`4/24/19
`
`5/1/19
`
`5/1/19
`
`5/9/19
`
`5/9/19
`
`5/9/19
`
`5/9/19
`
`5/9/19
`
`16
`
`

`

`Case 1:22-cv-01702-CJN Document 1 Filed 06/14/22 Page 17 of 21
`
`Ipamorelin
`acetate
`
`FDA-2015-N-
`3469-0293
`
`5/13/19
`
`www.regulations.gov/document?D=FDA-
`2015-N-3469-0293
`
`41.
`
`FDA also has not categorized the following 14 bulk drug substances which OFA
`
`nominated between June 2020 and December 2021:
`
`Substance
`
`Gonadorelin
`acetate
`Bimatoprost
`
`Fluoruracil
`
`Tranexamic acid
`
`Doxycycline
`hyclate
`
`Isotretinoin
`
`Nomination
`ID
`FDA-2015-N-
`3469-0311
`FDA-2015-N-
`3469-0326
`FDA-2015-N-
`3469-0324
`FDA-2015-N-
`Minocycline
`3469-0325
`hydrochloride