I thought I’d copy and paste the latest news from the FDA regarding the ZepBound drug shortage. This statement came out on December 19th…. Here is a link to take you there directly if you desire.
https://www.fda.gov/media/184606/download
December 19, 2024
Patty Donnelly, Ph.D.
Senior Vice President, Global Quality
Eli Lilly and Company
Lilly Corporate Center
Indianapolis, Indiana 46285
Sent by e-mail
Declaratory Order: Resolution of Shortages of Tirzepatide Injection Products (Mounjaro
and Zepbound)
Tirzepatide injection products were first added to FDA’s drug shortage list on December 15,
2022. The Agency determined that the shortage was resolved and removed tirzepatide injection
products from FDA’s drug shortage list on October 2, 2024.1 FDA has now reevaluated that
decision.2
This order has been prepared to allow for its public disclosure. It does not include any of the
confidential commercial information and/or trade secret information provided by Eli Lilly and
Company that FDA analyzed for the purpose of making the determination set forth herein.
This order revokes and replaces FDA’s October 2, 2024 decision on the same subject.
I. Determination
FDA determines that the tirzepatide injection product shortage is resolved. This determination is
based on the analysis set forth in FDA’s decision memorandum dated December 19, 2024,
“Resolution of Tirzepatide Injection Product Shortage and Supply Status,” (Decision
Memorandum”) and summarized below.
FDA is instructed to “maintain an up-to-date list of drugs that are determined by [FDA] to be in
shortage in the United States,”3 and a “shortage” is “a period of time when the demand or
projected demand for the drug within the United States exceeds the supply of the drug.”4 Eli
Lilly and Company (“Lilly”), the manufacturer of the relevant tirzepatide injection drug
1 https://dps.fda.gov/drugshortages/resolved/tirzepatide-injection
2 On October 7, 2024, FDA was sued in the U.S. District Court for the Northern District of Texas by the
Outsourcing Facilities Association and North American Custom Laboratories, LLC d/b/a Farmakeio Custom
Compounding regarding removal of tirzepatide injection from FDA’s drug shortages list. On October 11, 2024,
upon FDA’s motion, a court order remanded the decision to the Agency for reevaluation. See Outsourcing Facilities
Ass’n v. FDA, No. 4:24‐cv‐953, ECF Nos. 27, 28 (N.D. Tex.).
3 Section 506E(a) of the FD&C Act.
4 Section 506C(h)(2) of the FD&C Act; 21 CFR 314.81(b)(3)(iii)(f).
U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
w ww.fda.gov
products, has provided FDA with detailed information and data regarding its production and
inventory of these drug products at various points in time, including stock reports that show
quantities supplied and demanded, and inventory held in stock, for all strengths of these drug
products; cumulative quantities supplied to and demanded by its customers in the year 2024;
projected demand and supply in future months; and wholesaler inventory data, among other
information. We conclude that the information and data Lilly has provided to FDA demonstrate
that Lilly’s supply is currently meeting or exceeding demand for these drug products, and that
Lilly has developed reserves that it now holds in its finished product inventory, plus significant
units of semi-finished product, and has scheduled substantial additional production over the
coming months, such that supply will meet or exceed projected demand.
FDA has also considered potentially relevant information regarding the shortage determination
from patients, healthcare providers, and others, including compounders, along with data from
other sources that we independently identified. After carefully evaluating this information, we
find that it has important limitations. We conclude that this information does not undermine or
outweigh the evidence demonstrating that Lilly’s supply is currently meeting or exceeding
demand and that, based on our best judgment, it will meet or exceed projected demand.
For example, FDA received reports that some patients and pharmacists are not able to obtain the
approved drugs, and that a substantial amount of tirzepatide compounding is occurring. The
information provided in Lilly’s submissions demonstrate that the company is currently meeting
or exceeding demand for Mounjaro and Zepbound. That is not inconsistent with some, and even
many, individuals having had some trouble getting prescriptions for the affected drugs filled over
the course of the shortage, and some individuals may still be currently encountering such
challenges, even though Lilly’s supply is now meeting or exceeding demand nationally. In our
assessment, intermittent challenges of this kind are most likely explained not by a continuing
national shortage of supply, but by the practical dynamics of the portion of the supply chain
between Lilly and the individual customers, including wholesale distributors and retailers. We
recognize that significant compounding of tirzepatide injection products is occurring, and that
some number of patients currently receiving those products can be expected to seek Lilly’s
approved products at a future point when compounding is curtailed. However, the additional
information provided by patients, healthcare providers, and others, including compounders does
not demonstrate that Lilly will be unable to meet projected demand, especially when weighed
against the Lilly-provided data.
For all of these reasons and as explained further in the Decision Memorandum, we determine
that the shortage is resolved. Our determination is based on our conclusions that supply meets or
exceeds current demand, and that, based on our best judgment looking at the available
information with its limitations, supply will also meet or exceed projected demand.
FDA will continue to monitor supply and demand for these products, and whether any tirzepatide
injection products should be included on the drug shortage list in the future, as appropriate.5
5 Notwithstanding resolution of the shortage, FDA understands that patients and prescribers may still see
intermittent localized supply disruptions as the products move through the supply chain from the manufacturer to
wholesale distributors and pharmacies.
2
This order also explains that, in addition to the representations FDA made regarding enforcement
in October 2024 in connection with litigation,6 FDA does not intend to take action against
compounders for violations of the Federal Food, Drug, and Cosmetic Act (FD&C Act) arising
from conditions that depend on tirzepatide injection products’ inclusion on the FDA drug
shortage list (see section 506E of the FD&C Act) [i.e., section 503A(b)(1)(D) (compounded
drugs that are essentially a copy of a commercially available drug product) or sections
503B(a)(2)(A) (bulk drug substances used in compounding) and (a)(5) (compounded drugs that
are essentially a copy of an FDA‐approved drug product)] for the following time periods from
the date of this order:
• For state-licensed pharmacists or physicians compounding under section 503A of the
FD&C Act, 60 calendar days from the date of this order, until February 18, 2025; and
• For outsourcing facilities under section 503B of the FD&C Act, 90 calendar days from
the date of this order, until March 19, 2025.
II. Background
FDA maintains an up-to-date list of drugs that are determined by the Agency to be in shortage in
the United States.7 FDA’s drug shortage list is publicly available on the Agency’s website.8
FDA’s drug shortage list includes the names and National Drug Code (NDC) numbers for such
drugs; the name of each applicant for such drugs, the reason for the shortage as determined by
FDA, and the estimated duration of the shortage.9
In this context, a drug shortage means “a period of time when the demand or projected demand
for the drug within the United States exceeds the supply of the drug.”10 As such, in determining
whether a drug is in shortage for purposes of the FD&C Act, FDA evaluates the supply and
demand or projected demand of the drug on a nationwide level, across the entire market, not at
6 See Defendants’ Unopposed Motion for Voluntary Remand and Stay, Outsourcing Facilities Ass’n v. FDA, No.
4:24‐cv‐953, ECF No. 27, at 3. See also Letter from Gail Bormel, Office Director, CDER Office of Compounding
Quality and Compliance, to Scott Brunner, Chief Executive Officer, Alliance for Pharmacy Compounding (APC)
(Oct. 17, 2024), available at https://www.fda.gov/media/182948/download?attachment.
7 See section 506E(a) of the FD&C Act (21 U.S.C. 356e) and 21 CFR 314.81(b)(3)(iii)(d)(1). Manufacturers of
certain prescription drug products must notify FDA of a permanent discontinuance in the manufacture of the drug
product, or an interruption in manufacturing of the drug product that is likely to lead to a meaningful disruption in
supply of that drug in the United States, and the reasons for such discontinuance or interruption. For the same drugs,
manufacturers are also required to report a permanent discontinuance in the manufacture of an active pharmaceutical
ingredient of the drug or an interruption in the manufacture of an active pharmaceutical ingredient likely to lead to a
meaningful disruption in supply of the manufacturer’s drug, and the reasons for the discontinuance or interruption.
See section 506C of the FD&C Act and 21 CFR 314.81(b)(3)(iii).
8 https://dps.fda.gov/drugshortages. See section 506E(c) of the FD&C Act and 21 CFR 314.81(b)(3)(iii)(d)(1).
9 See section 506E(b) of the FD&C Act and 21 CFR 314.81(b)(3)(iii)(d)(1). FDA cannot disclose trade secret or
commercial or financial information that is considered confidential or privileged. See sections 506C(d) and
506E(c)(2) of the FD&C Act and 21 CFR 314.81(b)(3)(iii)(d)(2). Additionally, FDA may choose not to make drug
shortage information publicly available if FDA determines that disclosure of such information would adversely
affect the public health (such as by increasing the possibility of hoarding or other disruption of the availability of
drug products to patients). See section 506E(c)(3) of the FD&C Act and 21 CFR 314.81(b)(3)(iii)(d)(2).
10 Section 506C(h)(2) (21 U.S.C. 356c) of the FD&C Act; see also 21 CFR 314.81(b)(3)(iii)(f).
3
the local level.11 The Agency acknowledges that even when a shortage is considered resolved,
patients and prescribers may still see intermittent localized supply disruptions as products move
through the supply chain from the manufacturer and distributors to local pharmacies.
FDA receives input regarding drug shortages from numerous stakeholders, including
manufacturers, patients, healthcare providers, and others, including compounders.12 In particular,
manufacturers are required to notify FDA about discontinuances and manufacturing interruptions
pertaining to certain drugs pursuant to statutory and regulatory requirements,13 and they may
voluntarily provide additional information as relevant about quality issues, increases in demand,
recalls, or other events (e.g., relevant supply and demand conditions).
Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like
peptide-1 (GLP-1) receptor agonist. Mounjaro and Zepbound are the only FDA-approved
tirzepatide products. Mounjaro (tirzepatide) injection, for subcutaneous use, is indicated as an
adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Mounjaro is approved as pre-filled single-dose pens in several strengths (2.5 mg/0.5 mL, 5
mg/0.5 mL, 7.5 mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL, and 15 mg/0.5 mL). The Mounjaro
pen products were approved by FDA in May 2022 (NDA 215866) and added to FDA’s drug
shortage list in December 2022 due to high demand. Mounjaro single-dose vial products in the
same strengths were approved in a supplement to NDA 215866 in July 2023, but are not
currently marketed in the United States and have not been on FDA’s drug shortage list.
Zepbound (tirzepatide) injection, for subcutaneous use, is indicated in combination with a
reduced-calorie diet and increased physical activity to reduce excess body weight and maintain
weight reduction long term in adults with obesity or adults with overweight in the presence of at
least one weight-related comorbid condition. Zepbound is also approved as pre-filled single-dose
pens and single-dose vials in the same strengths as Mounjaro (2.5 mg/0.5 mL, 5 mg/0.5 mL, 7.5
mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL, and 15 mg/0.5 mL). The Zepbound pen products
were approved by FDA in November 2023 (NDA 217806) and added to FDA’s drug shortage
list in April 2024 due to high demand. The Zepbound single-dose vial products were approved in
a supplement to NDA 217806 in March 2024, but only the 2.5 mg and 5.0 mg strengths are
currently being marketed in the United States. The Zepbound vial products have never been on
the shortage list.
11 See FDA Strategic Plan for Preventing and Mitigating Drug Shortages (October 2013), available at
https://www.fda.gov/media/86907/download. See also CDER’s manual of policies and procedures on drug shortage
management (MAPP 4190.1 Rev. 4), available at https://www.fda.gov/media/72447/download; and FDA’s draft
guidance for industry, Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or
Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act (February 2024), available at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/notifying-fda-discontinuance-or-
interruption-manufacturing-finished-products-or-active. This draft guidance, when finalized, will represent FDA’s
current thinking on this topic.
12 FDA’s website includes information about drug shortage notifications for industry and a public portal for patients,
healthcare providers, and organizations to report new shortages, available at https://www.fda.gov/drugs/drug-safety-
and-availability/drug-shortages.
13 Section 506C(h)(2) of the FD&C Act; 21 CFR 314.81(b)(3)(iii)(f).
4
III. Procedural Considerations
This declaratory order is the product of an informal adjudication in which FDA evaluated the
information available to the agency to make a determination of the relevant facts regarding the
affected drug products, and applied the statutory standard for drug shortages to those facts.
Under 5 U.S.C. 554(e) (section 5(d) of the Administrative Procedure Act (APA)), an agency, “in
its sound discretion, may issue a declaratory order to terminate a controversy or remove
uncertainty.” The APA defines “order” as “the whole or a part of a final disposition, whether
affirmative, negative, injunctive, or declaratory in form, of an agency in a matter other than
rulemaking but including licensing.” 5 U.S.C. 551(6). The APA defines “adjudication” as
“agency process for the formulation of an order.” 5 U.S.C. 551(7). FDA’s regulations, consistent
with the APA, define “order” to mean “the final agency disposition, other than the issuance of a
regulation, in a proceeding concerning any matter . . . .” 21 CFR 10.3(a). Our regulations also
define “proceeding and administrative proceeding” to mean “any undertaking to issue, amend, or
revoke a regulation or order, or to take or not to take any other form of administrative action,
under the laws administered by the Food and Drug Administration.” 21 CFR 10.3(a). Moreover,
our regulations establish that the Commissioner may initiate an administrative proceeding to
issue, amend, or revoke an order. 21 CFR 10.25(b).
The statute does not explicitly provide the procedure FDA must use to make a determination
regarding whether a drug product is in shortage, or whether such a shortage has resolved. As
explained below, FDA has determined that its drug shortage authority is more compatible with
adjudication than with rulemaking, and, consistent with the agency’s past practice, FDA
continues to implement this authority through adjudication. “The choice between rule-making or
declaratory order is primarily one for the agency regardless of whether the decision may affect
policy and have general prospective application.” Viacom v. FCC, 672 F.2d 1034, 1042 (2d Cir.
1982). See also SEC v. Chenery, 332 U.S. 194, 203 (1947); NLRB v. Wyman-Gordon Co., 394
U.S. 759 (1969); NLRB v. Bell Aerospace Co., 416 U.S. 267, 294 (1974); Almy v. Sebelius, 679
F.3d 297, 303 (4th Cir. 2012); City of Arlington, Texas v. FCC, 133 S. Ct. 1863, 1874 (2013);
Qwest Servs. Corp. v. FCC, 509 F.3d 531, 536– 37 (D.C. Cir. 2007) (“Most norms that emerge
from a rulemaking are equally capable of emerging (legitimately) from an adjudication, and
accordingly agencies have very broad discretion whether to proceed by way of adjudication or
rulemaking” (internal citations and quotations omitted)). Courts “accord significant deference to
an agency’s characterization of its own action” when determining whether it is a rule or an order
for APA purposes. Am. Airlines, Inc. v. Dep’t of Transp., 202 F.3d 788, 797–98 (5th Cir. 2000)
(citing and quoting British Caledonian Airways, Ltd. v. Civil Aeronautics Bd., 584 F.2d 982, 992
(D.C. Cir. 1978) (“In the present case we have, moreover, the Board’s own assertion that its order
is purely interpretive, and this contention in itself is entitled to a significant degree of credence….
While declaratory orders differ in some respects from interpretive rules, the same rationale
should apply equally to an agency’s characterization of one of its rulings as a declaratory
order.”)).
Making a determination regarding drug shortage status in a declaratory order issued as a product
of informal adjudication is well within FDA’s discretion under the FD&C Act and the APA.
5
Whether an affected drug product is (or is no longer) in shortage is a “concrete and narrow
question[]”—in this case involving a drug product manufactured by a single pharmaceutical
company—“the resolution[] of which would have an immediate and determinable impact on
specific factual scenarios.” City of Arlington v. FCC, 668 F.3d 229, 243 (5th Cir. 2012); see also
Qwest Servs. Corp., 509 F.3d at 536–37; Chisholm v. FCC, 538 F.2d 349, 364–66 (D.C. Cir.
1976). FDA is issuing this declaratory order to remove uncertainty as to the status of the
shortages of tirzepatide injection drug products, specifically, Mounjaro 2.5 mg, 5.0 mg, 7.5 mg,
10 mg, 12.5 mg, and 15 mg; and Zepbound 2.5 mg, 5.0 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg.
This adjudication requires FDA to make determinations about the relevant facts, using the
information available to the agency, and apply the statutory standard for drug shortages to those
facts. Such applications of law to facts do not create new law and accordingly do not require
FDA to engage in rulemaking, even if they include some amount of interpretation. “The feature
which distinguishes declaratory orders and other interpretative rulings from those legislative
rules which must conform with the procedures established by the APA for rulemaking is not the
extent of their effect, but rather that the order or ruling instead of creating new law serves only to
clarify and state an agency’s interpretation of an existing statute or regulation.” British
Caledonian Airways v. Civil Aeronautics Board, 584 F.2d 982, 990 (D.C. Cir. 1978) (emphasis
added); see also Trans International Airlines v. Civil Aeronautics Board, 432 F.2d 607, 612 n.9
(D.C. Cir. 1970) (“an interpretation of . . . regulations by . . . declaratory ruling . . . [is] well
within the scope of the familiar power of an agency to interpret the regulations within the
framework of an adjudicatory proceeding”). In addition, the temporary nature of a shortage
determination is consistent with adjudication rather than rulemaking. See Goodman v. FCC, 182
F.3d 987, 994-5 (D.C. Cir. 1999) (upholding an order granting temporary waivers to companies
who were not named parties in the proceeding, and contrasting the temporary nature of the
waivers with a “general, prospective amendment” to existing rules as “a strong reason to
conclude the proceeding was not a rulemaking”).
The applicable statutory authorities are more consistent with adjudication than with rulemaking
in part because “adjudicatory decisions are not subject to the APA’s notice-and-comment
requirements.” Blanca Telephone Co. v. FCC, 743 F.3d 860 (D.C. Cir. 2014)). In rulemaking,
however, the APA typically requires agencies to “give interested persons an opportunity to
participate . . . through submission of written data, views, or arguments.” 5 U.S.C. § 553(c).
Notice to interested parties of their opportunity to do so requires the agency to “reveal[] for
public evaluation” the “‘technical studies and data’ upon which the agency relies.’” Chamber of
Commerce v. SEC, 443 F.3d 890, 899 (D.C. Cir. 2006) (quoting Solite Corp. v. EPA, 952 F.2d
473, 484 (D.C. Cir. 1991)). Under the APA, therefore, “[a]n agency commits serious procedural
error when it fails to reveal portions of the technical basis for a proposed rule in time to allow for
meaningful commentary.” Solite Corp., 952 F.2d at 484 (quoting Connecticut Light and Power
Co. v. NRC, 673 F.2d 525, 530–31 (D.C. Cir. 1982)). Put another way, rulemaking generally
requires an agency to “afford interested parties an opportunity to challenge the underlying factual
data relied on by the agency.” Chemical Mfrs. Ass’n v. EPA, 870 F.2d 177, 200 (5th Cir. 1989)
(citing Air Products & Chemicals, Inc. v. FERC, 650 F.2d 687, 700 n.17 (5th Cir. 1981)).
6
These notice-and-comment requirements are impossible to reconcile with the statutory
provisions governing a drug shortage determination. To begin, take the statutory section titled
“public availability,” 21 U.S.C. 356e(c). First, section 356e(c)(3) explicitly provides FDA with
discretion not to make the very existence of a shortage public. It states that FDA “may choose
not to make information collected under this section [356e] publicly available . . . if [FDA]
determines that disclosure of such information would adversely affect the public health (such as
by increasing the possibility of hoarding or other disruption of the availability of drug products
to patients).” The existence of a shortage itself, as well as factual information supporting the
determination of its existence, is “information collected” under section 356e, and the fact of a
shortage’s existence (rather than any particular factual detail supporting the determination of a
shortage) is the most obvious type of information that would be likely to cause hoarding when
publicly announced. Knowledge that a shortage exists may foreseeably incentivize people to, for
example, hoard product for their own or others’ use (thereby avoiding disruption for some
patients, but at the possible expense of other patients), or for financial gain (such as by selling
the product at increased prices due to scarcity). The statutory provision giving FDA discretion to
choose whether to make a shortage public based on these types of concerns is impossible to
reconcile with a requirement that FDA conduct notice-and-comment rulemaking. In such a
circumstance there could be no notice, no comment, and no public announcement of the decision
itself. By contrast, FDA could act consistently with the provision through an adjudication
process in which the agency made the necessary information available only to affected entities in
the product’s supply chain.
Second, a large amount of the information that FDA analyzes to determine the status of a drug
shortage is the drug manufacturer’s trade secret and/or confidential commercial information
which FDA may not publicly disclose under applicable laws and regulations. This includes
detailed information about current and future production, inventory, sales, and distribution. Such
information is, in most cases, closely held by the submitting company, which considers the
information privileged and confidential business information. Such information is exempt from
the public disclosure provisions of the Freedom of Information Act (FOIA) by exemption 4, see
5 U.S.C. 552(b)(4), and may not be disclosed by FDA because of protections in the Trade Secrets
Act, see 18 U.S.C. 1905, and FDA’s regulations. See, e.g., 21 C.F.R. 20.111(d)(3) (identifying
“production, sales, distribution, and similar data and information” submitted voluntarily to FDA
as “not available for public disclosure” subject to certain exceptions); 10.20(j)(2)(i)(d) (similar);
and 20.61 (further detailing FDA’s treatment of such information). In some cases, most, or even
all, of the factual materials that FDA considered, and which therefore make up the administrative
record, will be subject to disclosure-law protections. The statute’s “public availability” section
recognizes this reality and underscores that the requirement to publish the drug shortage list does
not alter or amend the disclosure restrictions in 18 U.S.C. 1905 or 5 U.S.C. 552(b)(4); see also
21 U.S.C. 356e(c)(2); Food Marketing Institute v. Argus Leader Media, 588 U.S. 427, 440
(discussing sales data, and concluding that “where commercial or financial information is both
customarily and actually treated as private by its owner and provided to the government under an
assurance of privacy, the information is ‘confidential’ within the meaning of [5 U.S.C.
552(b)(4)]”). Because, absent the drug manufacturer’s consent, FDA typically cannot proactively
7
publish confidential information about a drug’s current and future production, inventory, sales,
and distribution, notice and comment rulemaking is incompatible with drug shortage decisions.
Third, section 356e(c)(1)’s directive only that the agency “shall make the information in such list
publicly available” (subject to the significant exceptions discussed immediately above) is more
consistent with adjudication than rulemaking. The statute does not provide that the agency must
use rulemaking, or that it must publish its determination in the Federal Register. The APA
requires agencies to “make available for public inspection and copying” any “final opinions, . . .
as well as orders, made in the adjudication of cases,” 5 U.S.C. § 552(a)(2)(A), and if an order
contains “statements of general policy or interpretations of general applicability,” the agency
may need to publish the order in the Federal Register, 5 U.S.C. § 552(a)(1)(D). But the Federal
Register publication requirement does not apply to “interpretations of general applicability
[made] in the course of issuing adjudicatory opinions” in light of section 552(a)(2), which
requires only “public inspection and copying” of orders. See, e.g., Cheshire Hosp. v. New
Hampshire-Vermont Hospitalization Serv., 689 F.2d 1112, 1123 (1st Cir. 1982) (“Courts which
have been forced to harmonize these two provisions [§ 552(a)(1)(D) and § 552(a)(2)(D)] have
held that an agency may formulate interpretations of general applicability in the course of issuing
adjudicatory opinions without publishing such opinions in the Federal Register. The agency need
only make such opinions available to the public as provided for by 5 U.S.C. s 552(a)(2)(A).”)
(internal citations omitted).
Beyond the “public availability” statutory section, the requirement in 21 U.S.C. 356e(a) that the
Secretary maintain an “up-to-date” drug shortage list also, at a minimum, strongly suggests that
the authority is more consistent with adjudication than with rulemaking. Even if notice and
comment rulemaking were done expeditiously, that procedure plus a 30-day delayed effective
date, see 5 U.S.C. § 553(b)-(d), would not result in a drug shortage list that could fairly be
characterized as “up-to-date,” thereby potentially preventing the agency from fulfilling its
statutory mandate. While the APA contains a “good cause” exception to the notice-and-comment
and 30-day delayed effective date requirements, 5 U.S.C. § 553(b)(B), (d)(3), the exception’s
requirements have been stringently interpreted, which could introduce uncertainty about whether
a court will agree with the agency that good cause exists in a particular circumstance. See, e.g.,
State of N. J., Dep’t of Env’t Prot. v. U.S. Env’t Prot. Agency, 626 F.2d 1038, 1045 (D.C. Cir.
1980) (“exceptions to the notice-and-comment provisions of section 553 will be narrowly
construed and only reluctantly countenanced”). And even assuming that drug shortage decisions
would routinely qualify for the good cause exception, the most straightforward interpretation is
that Congress did not intend such decisions to be subject to notice-and-comment requirements at
all, rather than that Congress intended such decisions to be subject to, but routinely exempt from,
those requirements.
For all of these reasons, FDA considers the drug shortage list authority in 21 U.S.C. 356e to be
much more compatible with adjudication than rulemaking, and consistent with its approach to
date, the agency continues to choose to implement this authority through adjudication.
Finally, FDA notes that this order is a product of an informal adjudication that included notice to
affected parties via publication of the shortage determination on FDA’s website, and an
8
opportunity for affected parties to be heard by submitting information to the Agency for
consideration. The APA gives agencies discretion to determine the appropriate level of public
participation in agency decisions. See 5 U.S.C. 555(b) (“So far as the orderly conduct of public
business permits, an interested person may appear before an agency. . . for the . . . determination
of an issue”). Multiple interested parties, including the manufacturer of the affected drug
products, individual patients, pharmacy compounders, outsourcing facilities, associations
representing pharmacy compounders and outsourcing facilities, and telehealth companies, did in
fact submit information to the Agency, both before FDA’s initial announcement that these
shortages had resolved and during FDA’s reevaluation of that decision. The agency considered
those submissions in formulating this order. Such procedures are appropriate for the formulation
of declaratory orders and avoid the problems that would be presented by notice-and-comment
rulemaking, as described above. See, e.g., National Labor Relations Board v. Bell Aerospace,
416 U.S. 267, 295 (1975) (no procedural error where the parties “most immediately affected” by
the order were “accorded a full opportunity to be heard”).
IV. Status of Compounding Following this Decision
In connection with the litigation noted above,14 FDA stated that during the reevaluation and for a
period after the Agency makes its decision, FDA does not intend to take action against
compounders for violations of the FD&C Act arising from conditions that depend on tirzepatide
injection products’ inclusion on FDA’s drug shortage list, i.e., section 503A(b)(1)(D)
(compounded drugs that are essentially a copy of a commercially available drug product) or
sections 503B(a)(2)(A) (bulk drug substances used in compounding) and (a)(5)) (compounded
drugs that are essentially a copy of an FDA‐approved drug product).
In addition to that representation, as explained further below, to avoid unnecessary disruption to
patient treatment and to help facilitate an orderly transition, for the same violations described
above, FDA does not intend to take action against a compounder that is not registered as an
outsourcing facility for compounding, distributing, or dispensing tirzepatide injection products
that are essentially a copy of a commercially available drug product15 within 60 days of this
decision. In addition, FDA does not intend to take action against an outsourcing facility for use
of the bulk drug substance tirzepatide to compound, distribute, or dispense a drug product that
appeared on FDA’s drug shortage list,16 or for compounding, distributing, or dispensing
tirzepatide injection products that are essentially a copy of an FDA‐approved drug product,17
within 90 days of this decision.
Neither FDA’s statements in the court case, the court’s order, nor this order prevents FDA from
taking action for violations of any other statutory or regulatory requirements, such as to address
findings that a product may be of substandard quality or otherwise unsafe.
14 See Defendants’ Unopposed Motion for Voluntary Remand and Stay, Outsourcing Facilities Ass’n v. FDA, No.
4:24‐cv‐953, ECF No. 27, at 3. See also Letter from Gail Bormel, Office Director, CDER Office of Compounding
Quality and Compliance, to Scott Brunner, APC (Oct. 17, 2024), available at
https://www.fda.gov/media/182948/download?attachment.
15 See section 503A(b)(1)(D) of the FD&C Act.
16 See section 503B(a)(2)(A) of the FD&C Act.
17 See section 503B(a)(5) of the FD&C Act.
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The enforcement discretion described here is based on the following considerations.
First, as explained in FDA’s guidance documents, “Compounded Drug Products That Are
Essentially Copies of a Commercially Available Drug Product Under Section 503A of the
Federal Food, Drug, and Cosmetic Act” and “Compounded Drug Products That Are Essentially
Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and
Cosmetic Act,” the FD&C Act generally limits the compounding of drugs that are essentially
copies of commercially available and approved drugs, respectively.
Although compounded drug products can provide treatment options for patients during a drug
shortage, compounded drugs have not undergone FDA premarket review for safety,
effectiveness, and quality, and lack a premarket inspection and finding of manufacturing quality
that is part of the drug approval process. Further, drug products that meet the conditions under
section 503A are not subject to CGMP requirements and are subject to less robust production
standards that provide less assurance of quality. Accordingly, the statute includes restrictions on
compounding drugs that are essentially copies of commercially available drugs18 and approved
drug products that are not on FDA’s drug shortage list. These restrictions help reduce the risk
that compounders will prepare these unapproved drug products for patients whose medical needs
could be met by an approved product. This helps to protect patients from unnecessary exposure
to drugs that have not been shown to be safe and effective, and that offer fewer assurances of
manufacturing quality.
The copies restrictions also protect the integrity of the new drug and abbreviated new drug
(ANDA) approval processes by, for example, incentivizing sponsors to invest in and seek
approval of innovative, life-saving medications – by limiting the ability of compounders to, after
a drug is approved, compound “substitutes” that may be less expensive because they have not
had to demonstrate safety and effectiveness or be labeled with adequate directions for use, and,
for drugs compounded under section 503A, are not produced in accordance with CGMP
requirements.19
For the above reasons, an indefinite or overly long period of enforcement discretion for
continued compounding of drugs that may be essentially copies of an approved drug that is no
longer in shortage would not be appropriate.
FDA has also considered public health concerns and reliance interests (as discussed further
below), and the enforcement discretion described here takes those concerns into account. FDA
considers that the 60/90-day period described here will allow patients a reasonable amount of
time to transfer their prescriptions, as needed, to different pharmacies to obtain the FDA-
approved drug. Patients who used compounded tirzepatide injection products during the
18 For purposes of section 503A, FDA does not consider a drug on FDA’s drug shortage list to be “commercially
available.”
19 Less directly relevant in this case, involving copies of sterile injectable products, the copies restrictions also help
protect FDA’s drug monograph process by limiting the ability of compounders to produce drugs without having to
comply with monograph standards or CGMP requirements that apply to such products.
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shortage may otherwise face gaps in their ability to access treatment.20 The additional time will
allow local pharmacies to adjust their stocking and ordering patterns to adjust to new patterns of
patient demand, which should help to minimize local disruptions.21
FDA also recognizes that compounded versions of drugs on FDA’s drug shortage list can
provide an important treatment option to patients during the shortage, and that compounders who
prepare such drugs may be holding finished, compounded products, or inputs to compounded
drugs, when a shortage resolves and the approved drug is taken off FDA’s drug shortage list.
For example, the compounder may have compounded drugs that are essentially copies of the
approved drug and be waiting for the results of sterility tests before releasing them. FDA is
required by statute to maintain an “up-to-date list” of drugs in shortage, 21 U.S.C. § 356e(a), and
does not give advance notice of its decisions to move drugs on and off the list. In recognition of
this fact, FDA’s guidance for outsourcing facilities has previously described a brief period of
enforcement discretion at the end of a drug shortage to account for such materials to be sold
off.22
The above considerations are particularly relevant to the tirzepatide injection products shortage.
We note that the shortage was ongoing for some time,23 and compounders and other stakeholders
report that a significant amount of compounding has been occurring. Additionally, FDA’s re-
evaluation of the shortage decision in the context of litigation may have caused some uncertainty
about whether or when compounded copies would leave the market, slowing market transition. A
period of enforcement discretion should help facilitate an orderly transition, as the adjustments
described above take place. Although the 60/90-day period described here is longer than the
period previously described in FDA’s guidance documents, we conclude that it is justified in
light of the considerations described here, including the information FDA has reviewed in
connection with the tirzepatide injection products shortage. That this period is relatively brief
20 See October 3, 2024, letter from Scott Brunner, APC, to OCQC (docket no. FDA-2015-N-0030, document ID
FDA-2015-N-0030-8519), stating that a 60-day transition period “would allow for a smoother transition, giving
pharmacies time to contact prescribers for updated prescriptions and to navigate insurance prior authorization
processes” and “would prevent abrupt discontinuations in patient care that will undoubtedly result from the sudden
unavailability of compounded copies”; and October 7, 2024, letter from Scott Brunner, APC, and Ronna Hauser,
SVP, Policy and Pharmacy Affairs, National Community Pharmacists Association, to FDA, DSS, and OCQC
(docket no. FDA-2015-N-0030, document ID FDA-2015-N-0030-8520), stating that during a 60-day transition
period, “prescriptions can be authorized for the FDA-approved products, coverage determinations made by
insurance companies, and the FDA-approved products can be obtained by pharmacies to fill the prescriptions.”
21 FDA recognizes that local and regional conditions can make it difficult for patients to get a drug through their
local pharmacies, even if that drug is not in a nationwide shortage. FDA’s authorities relating to drug shortages are
limited to shortages that exist “in the United States,” that is, at the national level. Section 506E(a) of the FD&C Act.
Thus, FDA does not treat local or regional supply disruptions the same way as the Agency treats national shortages.
22 FDA’s guidance for outsourcing facilities provides a period of enforcement discretion of 60 days for orders
received during a drug shortage. See Guidance for Industry: Compounded Drug Products That Are Essentially
Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Jan. 2018),
at 8; Guidance for Industry: Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of
the Federal Food, Drug, and Cosmetic Act (Jan. 2017), at 7. FDA’s guidance document for section 503A
compounders, Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product
Under Section 503A of the Federal Food, Drug, and Cosmetic Act (January 2018) does not address FDA’s
enforcement policy for this provision at the end of a drug shortage. CDER is currently re-evaluating these policies
pertaining to removal of compounded drugs from the market at the end of a shortage.
23 Since December 15, 2022.
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also mitigates concerns about potential effects on patients, the integrity of the drug approval
process, and any reliance interests of the approved drug manufacturer. While the approved drug
manufacturer may have an interest in FDA providing only the more limited enforcement
discretion stated in the Agency’s existing guidances, FDA has considered any such reliance
interest and concludes that it is outweighed by the reasons discussed here that otherwise support
this brief additional period of enforcement discretion.
The amount of time FDA intends to exercise enforcement discretion is longer for outsourcing
facilities (90 days) than for those compounding under 503A (60 days) because:
• Drugs compounded in outsourcing facilities under section 503B provide more assurances
of quality than drugs compounded under section 503A because they are made in facilities
registered with FDA that are subject to FDA inspection and cGMP requirements.
• FDA understands that outsourcing facilities need to invest relatively more resources and
time before they can produce product during a shortage because of these quality
standards.
V. Conclusion
FDA has determined that the shortage of tirzepatide injection products, which first began in
December 2022, is resolved. FDA continues to monitor supply and demand for these products.
Sincerely,
Patrizia Cavazzoni, M.D.
Director
Center for Drug Evaluation and Research
CC: Lee Rosebush, Chairman, Outsourcing Facilities Association
Dan DeNeui, Chief Executive Officer and Managing Partner of North American Custom
Laboratories, LLC d/b/a FarmaKeio Custom Compounding
Scott Brunner, Chief Executive Officer, Alliance for Pharmacy Compounding
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