Ipsen Biopharmaceuticals, Inc. v. Xavier Becerra, in His Official Capacity As Secretary of Health and Human Services

United States Court of Appeals
FOR THE DISTRICT OF COLUMBIA CIRCUIT
Argued April 1, 2024 Decided July 9, 2024
Reissued July 25, 2024
No. 23-5142
IPSEN BIOPHARMACEUTICALS, INC.,
APPELLANT
v.
XAVIER BECERRA, IN HIS OFFICIAL CAPACITY AS SECRETARY
OF HEALTH AND HUMAN SERVICES, ET AL.,
APPELLEES
Appeal from the United States District Court
for the District of Columbia
(No. 1:22-cv-00860)
Catherine E. Stetson argued the cause for appellant. With
her on the briefs were Susan M. Cook, Marlan Golden, and
Dana A. Raphael.
Urja Mittal, Attorney, U.S. Department of Justice, argued
the cause for federal appellees. With her on the brief were
Brian M. Boynton, Principal Deputy Assistant Attorney
General, Daniel Tenny, Attorney, and Samuel R. Bagenstos,
General Counsel, U.S. Department of Health & Human

-- 1 of 20 --

2
Services. Anna O. Mohan, Senior Counsel, U.S. Department
of Justice, entered an appearance.
Brian T. Burgess argued the cause for appellee InvaGen
Pharmaceuticals, Inc. With him on the brief was Gerard J.
Cedrone.
Before: WILKINS, KATSAS and RAO, Circuit Judges.
Opinion for the Court filed by Circuit Judge WILKINS.
WILKINS, Circuit Judge: In 2007, the Food and Drug
Administration (“FDA”) approved Ipsen Biopharmaceuticals,
Inc.’s application to sell Somatuline Depot as a drug product
under the Federal Food, Drug, and Cosmetic Act (“FDCA”).
This approval gave Somatuline Depot a period of market
exclusivity, and the FDA did not authorize any competing
generic forms of the drug for over a decade.
That changed in 2021 when the FDA approved an
application filed by InvaGen Pharmaceuticals, Inc., one of
Ipsen’s competitors, to sell a generic version of Somatuline
Depot under the FDCA. This approval ended Somatuline
Depot’s era of market exclusivity. At the heart of this dispute,
is Ipsen’s belief that Somatuline Depot should still enjoy
market exclusivity.
Here, Ipsen argues that the FDA’s classification of its
product violated the Administrative Procedure Act (“APA”).
In Ipsen’s view, Somatuline Depot is not a drug product subject
to the FDCA; it is a biologic and must be regulated under the
Public Health Service Act (“PHSA”). Had the FDA correctly
regulated Somatuline Depot, Ipsen further argues, the FDA
could not have approved InvaGen’s application under the
FDCA.

-- 2 of 20 --

3
Two of Ipsen’s prayers for relief are relevant to this appeal:
(1) declaratory judgment that the FDA’s refusal to reclassify
Somatuline Depot as a biologic was arbitrary, capricious, and
contrary to law in violation of the APA, and (2) vacatur of the
FDA’s approval of InvaGen’s application to sell a generic
version of Somatuline Depot. The District Court rejected
Ipsen’s arguments and granted summary judgment to the
government and InvaGen, which intervened to defend its
interest in keeping the generic Somatuline Depot on the market.
We agree with the result and, for reasons explained in the
opinion, affirm.
I.
A.
This case involves two statutory schemes, and a few
regulations, that establish the processes for obtaining FDA
approval of drug products and biological products. Both drugs
at issue in this case (Ipsen’s and InvaGen’s, respectively) were
approved under the FDCA, which governs drugs. But Ipsen
wants the FDA to reclassify its drug, Somatuline Depot, as a
biologic subject to the PHSA. If such a reclassification were
to occur, the FDA’s approval of InvaGen’s generic version of
Somatuline Depot could be jeopardized. The difference in the
statutory schemes explains why.
We begin with the FDCA. It forbids the sale of “any new
drug” without FDA approval. 21 U.S.C. § 355(a). This
approval is conditioned on the FDA evaluating the application
to sell the drug and, ultimately, concluding that the drug is safe
and effective for its intended uses. Id. § 355(b)(1)(A),
355(d)(2). Two of the FDCA’s three pathways to FDA
approval are relevant here: the innovator pathway and the
generic pathway.

-- 3 of 20 --

4
Ipsen took the innovator pathway: it filed a New Drug
Application and included its own clinical data that
demonstrated Somatuline Depot’s efficacy and safety. See id.
§ 355(b)(1). After receiving FDA approval, Ipsen, as an
innovator, enjoyed a period of market exclusivity where it sold
Somatuline Depot without having to compete with any generic
forms of the drug.
InvaGen, however, took a generic pathway that became
available once Ipsen’s exclusivity period concluded. In taking
this route, InvaGen’s application demonstrated that its product
had the same “active ingredient, route of administration,
indication, dosages and strengths” of Somatuline Depot. J.A.
28. Because Somatuline Depot served as the reference product,
InvaGen was able to show its product’s efficacy and safety by
relying on the same clinical research that Ipsen provided to the
FDA. See 21 U.S.C. § 355(b)(2).
We can now turn to the PHSA, which shares some
similarities with the FDCA. See 42 U.S.C. § 262. Similar to
approval under the FDCA, one pathway to approval under the
PHSA requires the manufacturer to demonstrate that its product
is “safe, pure, and potent” and its production facility is
“designed to assure that the biological product continues to be
safe, pure, and potent.” 42 U.S.C. § 262(a)(2)(C)(i)(I)–(II).
The PHSA’s other approval pathway is, likewise, similar to the
FDCA in that it permits a manufacturer to show that its product
is “highly similar to the reference product” by submitting data
that shows that “there are no clinically meaningful differences
between the biological product and the reference product in
terms of … safety, purity, and potency.” Id. § 262(i)(2). We
note a final similarity between the two approval processes:
when determining what the product is (a drug or biologic) the
FDA analyzes the product’s “active ingredient,” defined as
“any component that is intended to furnish pharmacological

-- 4 of 20 --

5
activity or other direct effect in the diagnosis, cure, mitigation,
treatment, or prevention of disease.” 21 C.F.R. § 314.3(b).
But there is also a significant difference in the two approval
processes. Under the PHSA, unlike the FDCA, manufacturers
must conduct their own clinical studies. This distinction in
approval processes sits at the crux of this case. If Somatuline
Depot were regulated under the PHSA, then InvaGen’s generic
product would not have been able to use Ipsen’s clinical studies
to achieve FDA approval. The PHSA does not permit
piggybacking.
The difference in approval processes makes sense.
Biologics are “a type of drug derived from natural, biological
sources such as animals or microorganisms. Biologics thus
differ from traditional drugs, which are typically synthesized
from chemicals.” Sandoz, Inc. v. Amgen Inc., 582 U.S. 1, 6
(2017). Indeed, a “biological product” is narrowly defined
under the PHSA as a “virus, therapeutic serum, toxin, antitoxin,
vaccine, blood, blood component or derivative, allergenic
product, protein, or analogous product … applicable to the
prevention, treatment, or cure of a disease or condition of
human beings.” 42 U.S.C. § 262(i)(1). Whereas the FDCA
defines a “drug” more broadly as an “article[] intended for use
in the diagnosis, cure, mitigation, treatment, or prevention of
disease in man” or “intended to affect the structure or any
function of the body of man.” 21 U.S.C. § 321(g)(1)(B), (C).
The type of biological products that are relevant here are
proteins and analogous products. The FDA defines a “protein”
as “any alpha amino acid polymer with a specific, defined
sequence that is greater than 40 amino acids in size. When two
or more amino acid chains in an amino acid polymer are
associated with each other in a manner that occurs in nature,
the size of the amino acid polymer … will be based on the total

-- 5 of 20 --

6
number of amino acids in those chains.” 21 C.F.R.
§ 600.3(h)(6). The FDA has not provided a definition for a
product that is “analogous” to a protein, and instead leaves
itself the space to make case-by-case determinations. J.A. 480–
81. At a minimum, however, the FDA takes the position that a
product that is analogous to a protein shares its “critical
characteristics.” J.A. 480.
B.
Ipsen’s drug, Somatuline Depot, “effects an extended-
release dosing of its active ingredient lanreotide acetate, a
molecule that mimics the naturally occurring hormone
somatostatin.” Ipsen Biopharmaceuticals, Inc. v. Becerra, 678
F. Supp. 3d 20, 27 (D.D.C. 2023) (internal quotation marks
omitted) (Ipsen II). During manufacture, the lanreotide acetate
(an eight amino acid polymer) in Somatuline Depot assembles
into structures known as nanotubes. The solution is then
injected into the body where it forms a depot under the skin that
“diffuses specific amounts of lanreotide into circulation in the
body over an extended period of time.” Id. at 39 (internal
quotation marks omitted). Recall that the FDA approved, and
regulates, Somatuline Depot as a drug under the FDCA.
In March 2020, pursuant to the Biologics Price
Competition and Innovation Act, the FDA reclassified drugs
that were originally approved and regulated under the FDCA
to “biological products” under the PHSA if these products met
the PHSA’s definition of a biological product. Somatuline
Depot did not make the cut. In response, Ipsen asked the FDA
to reconsider its decision to leave Somatuline Depot off of the
reclassification list. The FDA refused Ipsen’s reconsideration
request. So Ipsen sued. It argued that the FDA’s refusal to
transition Somatuline Depot from a drug product to a biological
product violated the APA. See Ipsen Biopharmaceuticals, Inc.

-- 6 of 20 --

7
v. Becerra, No. 20-cv-2437, 2021 WL 4399531, at *3 (D.D.C.
Sept. 24, 2021).
In September 2021, the District Court dismissed that suit
because Ipsen did not have standing. Relevant here is the
District Court’s conclusion that Ipsen’s lawsuit rested on a
“highly speculative fear that” at least one company would
apply to “market a generic version of Somatuline Depot,” that
the FDA would approve such an application, and the approved
generic version would not satisfy the PHSA’s demanding
requirement to show that it is highly similar to Somatuline
Depot. Id. at *4 (internal quotation marks omitted). In short,
Ipsen could not demonstrate that the FDA’s refusal to
reclassify Somatuline Depot constituted an injury because
there was no generic version of Somatuline Depot on the
market.
But a few months later, in December, the FDA approved
InvaGen’s application to sell a generic version of Somatuline
Depot. In response, Ipsen sued the FDA again. As it did in its
previous suit, Ipsen argued that when Somatuline Depot is in
its final dosage form, the lanreotide acetate assembles into
nanotube structures in a manner that occurs in nature and, once
in these nanotube assemblies, the lanreotide acetate chains
have over forty amino acids. See Ipsen II, 678 F. Supp. 3d at
35–36. The FDA’s conclusion to the contrary, Ipsen argued,
violated the APA because it was arbitrary and capricious. See
5 U.S.C. § 706(2)(A). In the alternative, Ipsen argued that
Somatuline Depot was analogous to a protein, and the FDA’s
interpretation and application of Section 262(i)(1) concluding
otherwise violated the APA because it was not in accordance
with law. Id.; see also Ipsen II, 678 F. Supp. 3d at 40.
This time, assured of its jurisdiction under Article III and
the federal question statute, see 28 U.S.C. § 1331, the District

-- 7 of 20 --

8
Court resolved the case at summary judgment1 in favor of the
FDA and InvaGen. First, the District Court rejected Ipsen’s
argument that the FDA was legally required to evaluate
whether lanreotide acetate had over eight amino acids in
Somatuline Depot’s final dosage form. See Ipsen II, 678 F.
Supp. 3d at 36–38. It also rejected Ipsen’s argument that
Somatuline Depot is a protein because, the District Court
found, Somatuline Depot’s active ingredient, lanreotide
acetate, is an eight amino acid chain; and eight is less than
forty. Id. at 38–40. Last, the District Court rejected Ipsen’s
argument that the FDA’s interpretation of “analogous” to a
protein, under Section 262(i)(1), rendered the word
“analogous” superfluous. Id. at 40–41. Having rejected all of
Ipsen’s arguments, the District Court concluded that the FDA’s
decision to regulate Somatuline Depot as a drug product did
not violate the APA. Id. at 41. This appeal followed.
II.
We begin with Ipsen’s lead argument: the FDA’s refusal to
transition Somatuline Depot to regulation as a biological
product was “arbitrary” and “capricious” in violation of the
APA. In analyzing the FDA’s decision, we “must be careful
not to unduly second-guess an agency’s scientific judgments,”
and will affirm the FDA’s decision so long as it is “reasonable
and reasonably explained.” Cytori Therapeutics, Inc. v. FDA,
715 F.3d 922, 923, 926 (D.C. Cir. 2013); see also Motor
Vehicle Mfrs. Ass’n v. State Farm Mut. Auto. Ins. Co., 463 U.S.
29, 43 (1983). We begin with the parties’ multiple points of
1 This was a final judgment that gives rise to our jurisdiction under
28 U.S.C. § 1291. We review this judgment de novo. See Cigar
Ass’n of Am. v. FDA, 964 F.3d 56, 61 (D.C. Cir. 2020) (“When a
district court reviews agency action under the APA, we in turn
review the district court’s decision de novo.”).

-- 8 of 20 --

9
agreement so that we can clearly articulate the precise issue that
we are asked to resolve.
The parties largely agree on the law. All agree that the
relevant statute is 42 U.S.C. § 262(i)(1), which recognizes that
a protein is a biological product. Ipsen also does not challenge
the FDA’s final rule defining a protein as “any alpha amino
acid polymer with a specific, defined sequence that is greater
than 40 amino acids in size. When two or more amino acid
chains in an amino acid polymer are associated with each other
in a manner that occurs in nature, the size of the amino acid
polymer … will be based on the total number of amino acids in
those chains.” 21 C.F.R. § 600.3(h)(6). The parties further
agree that the relevant question is whether a drug’s active
ingredient meets the FDA’s definition of a protein. And all are
in accord that an “active ingredient” is “any component that is
intended to furnish pharmacological activity.” 21 C.F.R. §
314.3(b).
There is similarly broad agreement on how the law applies
to the facts. All agree that Somatuline Depot’s active
ingredient is lanreotide acetate. There is no dispute that
lanreotide acetate is an “octapeptide” that contains eight amino
acids. J.A. 469. The parties also agree that when Somatuline
Depot is in its finished dosage form, the lanreotide acetate is
organized into a nanotube structure that contains more than 40
amino acids, but the nanotubes themselves do not confer any
pharmacological effect. See J.A. 472–74; Oral Arg. 2:55–3:30.
Given the extent of agreement on both facts and law, the
FDA and InvaGen advance an intuitive and straightforward
argument: the FDA reasonably concluded and adequately
explained that the nanotube structures do not confer any
pharmacological effect; therefore, Somatuline Depot’s active
ingredient is simply lanreotide acetate—an eight amino acid

-- 9 of 20 --

10
chain. Because eight is less than forty, lanreotide acetate is not
a protein, and Somatuline Depot is not a biologic. Case closed.
Alas, we find disagreement. In Ipsen’s view, the FDA and
InvaGen have ignored Section 262(i)’s relevant reference
point: the biological product. “Product,” Ipsen posits, refers to
a “drug product,” which the FDA defines as “a finished dosage
form.” 21 C.F.R. § 314.3(b). Putting these two definitions
together, Ipsen argues that the FDA was required to count
Somatuline Depot’s amino acids in its final dosage form. And
in the final dosage form, lanreotide acetate is organized into
nanotube structures “in a manner that occurs in nature.” 21
C.F.R. § 600.3(h)(6). From these premises, two conclusions
necessarily follow: (1) these nanotube structures in Somatuline
Depot’s final dosage form contain over forty amino acids,
therefore (2) lanreotide acetate is a protein, and Somatuline
Depot is a biologic.
From this disagreement, we find the question presented:
Did Congress silently incorporate the FDA’s definition of a
“drug product” under 21 C.F.R. § 314.3(b) into its definition of
a “biological product” under 42 U.S.C. § 262(i)? As with all
questions of statutory interpretation, “we begin with the text.”
City of Clarksville v. FERC, 888 F.3d 477, 482 (D.C. Cir.
2018); see also Sandoz Inc. v. Becerra, 57 F.4th 272, 280 (D.C.
Cir. 2023). Here, we start with the Congress’s separate
definitions for a “drug,” and a “drug product” under the FDCA.
Compare 21 U.S.C. § 321(g)(1) (defining a drug) with id.
§ 321(dd) (defining drug product).
Congress defines a “drug” as an “article[] intended for use
in the diagnosis, cure, mitigation, treatment, or prevention of
disease in man” or “intended to affect the structure or any
function of the body of man.” Id. § 321(g)(1)(B), (C). And to
determine whether an “article” is a “drug,” the FDA looks to
the “active ingredient,” i.e., “any component that is intended to

-- 10 of 20 --

11
furnish pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment, or prevention of disease,
or to affect the structure or any function of the body of man.”
21 C.F.R. § 314.3.
The definition of a drug product, however, has nothing to
do with the drug’s impact on the body. Rather, it cross-
references other statutory schemes that set forth the procedures
that manufacturers follow to receive FDA approval: “For
purposes of sections 335a and 335b of this title, the term ‘drug
product’ means a drug subject to regulation under section 355,
360b, or 382 of this title or under section 262 of Title 42.” Id.
§ 321(dd). In turn, the FDA defines a drug product as “a
finished dosage form, e.g., tablet, capsule, or solution, that
contains a drug substance, generally, but not necessarily, in
association with one or more other ingredients.” 21 C.F.R.
§ 314.3(b) (emphasis added).
From these two definitions and regulations, we identify an
important distinction: a drug furnishes pharmacological
activity, but a drug product is the “thing” ingested or
administered. Said another way, you must ingest the drug
product to reap the drug’s benefits. The FDA regulates both,
drugs and drug products. Hence, when a manufacturer applies
for new drug approval, the manufacturer can identify the “drug
substance (active ingredient) patent or a drug product
(formulation or composition) patent.” 21 U.S.C. §
355(b)(1)(A)(viii)(I) (emphasis added).
To better understand this distinction, consider Tylenol Cold
and Flu medicine. The active ingredients in Tylenol Cold and
Flu are acetaminophen, dextromethorphan, guaifenesin, and
phenylephrine. Label: Tylenol Cold Plus Flu Severe and
Tylenol Cold Max, NAT’L LIBR. MED., https://perma.cc/DG6P-
54ZZ. And these active ingredients remain the same whether
the drug is ingested as a liquid, see id., or as a tablet, see Label:

-- 11 of 20 --

12
Tylenol Cold and Flu-acetaminphen tablet, film coated, NAT’L
LIBR. MED., https://perma.cc/3UJF-GPWN. But Tylenol Cold
and Flu as a liquid is a different drug product than Tylenol Cold
and Flu as a tablet—even though both, liquid and tablet, are the
same drug.
Thus, we see two critical takeaways. First, the FDA does
not determine whether Tylenol Cold and Flu (or any other
product) is a drug by looking at its final dosage form. That
decision is made by looking at the drug’s active ingredient.
Full stop. Second, the FDA must determine whether the “drug
is safe for use and whether such drug is effective in use.” 21
U.S.C. § 355(b)(1)(A)(i) (emphasis added); see also id.
§ 355(d), (e). This requires analyzing the drug product.
Indeed, Tylenol Cold and Flu is approved for use as a solution
or a tablet—and in both events remains the same drug—but
there is no eye drop version of the drug product.
Now let’s turn to a biological product, which Congress
defines as a “virus, therapeutic serum, toxin, antitoxin, vaccine,
blood, blood component or derivative, allergenic product,
protein, or analogous product, or arsphenamine or derivative
of arsphenamine (or any other trivalent organic arsenic
compound), applicable to the prevention, treatment, or cure of
a disease or condition of human beings.” 42 U.S.C. § 262(i)(1)
(emphasis added).
This definition clearly shows that a “biological product” is
quite distinguishable from a “drug product.” Congress
explicitly identified an “analogous product” as one example of
a “biological product.” This identification supports the FDA’s
reasoning that each of the items specified in the preceding list
is itself a “product.” Indeed, a “protein,” like a “virus,” a
“therapeutic serum,” or an “antitoxin,” is itself a “product”
within the scope of Congress’s definition of a “biological
product.”

-- 12 of 20 --

13
The fact that Congress instructs the FDA to regulate
biological products as “drug products” is not at all inconsistent
with our read of the statute. 42 U.S.C. § 262(j). Our critical
takeaways are instructive, once again. The FDA must first
determine whether the product is a “biologic,” then it must
examine how the biologic is ingested or administered—that is,
how the biologic operates in use to determine if the product is
“safe, pure, and potent.” 42 U.S.C. § 262(a)(2)(C)(i)(I). In
Ipsen’s case, whether Somatuline Depot is “safe, pure, and
potent” in its finished dosage form is a separate question from
whether it is a “biological product.”
Recall that the parties agree that the FDA must look to the
active ingredient to determine whether a product is a biologic;
here, lanreotide acetate, an eight amino acid chain. While
Ipsen argues that the FDA’s refusal to analyze lanreotide
acetate when it is in nanotube structures was arbitrary and
capricious, it does not dispute the FDA’s scientific conclusion
that these nanotubes have no pharmacological effect. And we
all know that eight is less than forty, therefore, lanreotide
acetate is not a protein. The FDA and InvaGen are correct:
Case closed.
Ipsen’s attempt to merge the FDA’s definition of a “drug
product,” from a regulation interpreting a different statute, to
trump the definition of a “biological product” specified by
Congress in the relevant statute just does not work. This much
is evident by simply looking to Ipsen’s submissions to the FDA
when it sought to have Somatuline Depot approved as a new
drug. In that application, Ipsen relied on studies involving
other formulations of lanreotide acetate, including an
immediate-release version that did not assemble into
nanotubes. Or put plainly, no matter the finished dosage
form—whether in nanotube structures or otherwise—
lanreotide acetate’s pharmacological effect remained the same.
J.A. 472–73.

-- 13 of 20 --

14
And there’s the rub. Under Ipsen’s argument, Somatuline
Depot qualifies as a biological product when it is evaluated in
its finished dosage form. But other products, with the same
active ingredient, would remain as drug products. What text
supports this contradiction? After all, we see that Tylenol, no
matter its finished dosage form, remains a drug.
Ipsen cannot resolve the killer contradiction that its
argument compels. At best, Ipsen argues that a biological
product must be evaluated as if it were a drug product because,
in the preamble to the proposed rule defining a biological
product, the FDA explained that “the associated amino acid
chains ‘would be added together to determine whether the
product meets the numerical threshold.’” Ipsen Br. at 28
(quoting J.A. 294). But that argument falls flat because the
final rule includes no such explanation. And Ipsen does not
argue that the FDA violated the APA because the final rule was
not the logical outgrowth of the proposed rule. See, e.g., Shell
Oil Co. v. EPA, 950 F.2d 741, 747 (D.C. Cir. 1991).
Scouring for a different textual hook, Ipsen cites to 42
U.S.C. § 262(j) and 21 U.S.C. § 321(g) and argues that
biological products are merely types of drug products under
those statutes. Ipsen Reply at 7. But even so, that does not
mean Congress silently incorporated the FDA’s definition of a
“drug product” into the definition of a “biological product.”
More importantly, it does not indicate that biological products
should be classified based on their dosage form, rather than
their active ingredient.
Given the absence of authority supporting Ipsen’s legal
argument, we are left with, and return to, the points of
agreement. The parties are fine with the FDA’s definition of a
protein—“any alpha amino acid polymer with a specific,
defined sequence that is greater than 40 amino acids in size.”
21 C.F.R. § 600.3(h)(6). The parties agree that the FDA must

-- 14 of 20 --

15
determine whether the product’s “active ingredient” meets this
definition. There is no dispute as to the FDA’s definition of
“active ingredient”—“any component that is intended to
furnish pharmacological activity.” 21 C.F.R. § 314.3. Ipsen
does not challenge the FDA’s scientific judgment that the
nanotube structures confer no pharmacological effect. Finally,
Ipsen readily acknowledges that Somatuline Depot’s active
ingredient is lanreotide acetate, an eight amino acid polymer.
Thus, there can be no dispute that lanreotide acetate is not
a protein. The District Court correctly granted summary
judgment to the FDA and InvaGen.
III.
Ipsen also offers an argument in the alternative: Somatuline
Depot is “analogous” to a “protein” and, therefore, qualifies as
a biological product. Again, a “biological product” is defined
as a:
virus, therapeutic serum, toxin, antitoxin, vaccine, blood,
blood component or derivative, allergenic product, protein,
or analogous product, or arsphenamine or derivative of
arsphenamine (or any other trivalent organic arsenic
compound), applicable to the prevention, treatment, or cure
of a disease or condition of human beings. 42 U.S.C. §
262(i)(1).
The FDA has not promulgated a final rule defining
“analogous product.” Rather, it stakes out the general position
that it is inappropriate “to interpret the statutory term
‘analogous product’ (with reference to a ‘protein’) in a way that
would include amino acid polymers that are specifically
excluded by the interpretation of the term ‘protein’ in the
regulation.” FDA Brief at 26. Affirmatively, the FDA
contends that “[t]o be analogous to a category of biological
products, a product must share the critical characteristics of the

-- 15 of 20 --

16
relevant category of biological product.” J.A. 480. As to
proteins, the FDA asserts that “one such critical characteristic
is the size of the amino acid polymer;” and “a specific, defined
sequence” is another. J.A. 480–81. As an example of a product
that is “analogous to a protein,” the FDA points to “naturally
derived mixtures … that include one or more identified
biological product component(s) (e.g., protein), as well as one
or more non-biological product component(s) (e.g., lipids) that
can contribute to the product’s activity.” J.A. 481. These
“naturally derived mixtures” fit the bill, the FDA concludes,
because they “contain a protein, but are not known to be
composed primarily of protein components as their active
ingredient.” J.A. 481.
We need not search for disagreement on this issue. Ipsen
begins with a forceful argument that the FDA’s interpretation
of “analogous protein” reads “analogous” out of the statute. In
its view, the FDA effectively argues that the only products that
are “analogous” to proteins are actually proteins. Thus, by
concluding that Somatuline Depot is not a protein, it
necessarily followed that the FDA would conclude that
Somatuline Depot was not analogous to a protein either, Ipsen
continues. Such a conclusion is not in accordance with law,
Ipsen concludes, because Somatuline Depot “[i]n its finished
dosage form—the one that is sold in commerce and
administered to patients—the active ingredient lanreotide
acetate meets all of the definitional requirements of a protein.”
Ipsen Brief at 40.
The District Court sided with the FDA. It reasoned that the
FDA’s interpretation of “analogous” could not have been
superfluous even if Ipsen is correct that the FDA’s reading
“leaves empty the set of products that are analogous to but not
actually proteins.” Ipsen II, 678 F. Supp. 3d at 40. “The
statutory term would still include those products that the FDA
has explicitly defined as analogous to a virus, therapeutic

-- 16 of 20 --

17
serum, toxin, or antitoxin,” the District Court further explained.
Id.; see also id. at 41 (referencing United States v. Turkette, 452
U.S. 576, 583 n.5 (1981) (“Language in a statute is not
rendered superfluous merely because in some contexts that
language may not be pertinent.”)). But “[i]n any event,” the
District Court held that the FDA’s interpretation did not render
“analogous” superfluous even with respect to proteins. Id. at
41. That is because the FDA identified “drugs with active
ingredients that are comprised of certain naturally derived
mixtures that include one or more protein(s) as well as one or
more non-biological product component(s) (e.g., lipids)” as
analogous to proteins. Id. (internal quotation marks omitted).
We agree with Ipsen that “analogous product” includes
“analogous proteins.” “[T]he natural construction of the
language demands that [or analogous product] be read as
applicable” to the listed examples that precede it. Paroline v.
United States, 572 U.S. 434, 447 (2014); see also Teva
Pharmaceuticals USA, Inc. v. FDA, 514 F. Supp. 3d 66, 115
(D.D.C. 2020) (“The ‘analogous product’ provision requires
that some products not capable of identification as proteins be
capable of identification as analogous products, and that the
classification be based on some defining feature of proteins that
analogous products share.”). Here, “or analogous product”
immediately follows “a virus, therapeutic serum, toxin,
antitoxin, vaccine, blood, blood component or derivative,
allergenic product, [and] protein,” 42 U.S.C. § 262(i)(1), it
therefore follows that any product analogous to these terms is
a biologic.
Because Ipsen is correct that “analogous products” include
“analogous proteins,” we must consider its argument that the
FDA’s application of “analogous protein” to Somatuline Depot
is contrary to law. Ipsen’s general point is that a product is
“analogous” to a protein even if it has less than forty amino
acids, so long as it is “an alpha amino acid polymer with a

-- 17 of 20 --

18
specific, defined sequence and is composed of multiple amino
acid chains.” Ipsen Brief at 40. The FDA’s refusal to apply its
definition of analogous protein to Somatuline Depot, Ipsen
argues, was not in accordance with law. We disagree.
First, the FDA did not read “analogous” out of the statute.
It specifically provided an example of a product that was
analogous to a protein—a “naturally derived mixture[]” that
“contain[s] a protein” even though its active ingredient is
composed of more than “protein components.” J.A. 481
(emphasis removed). Ipsen’s rebuttal that this mixture is a
protein is unfairly reductive—quite simply, this mixture is a
mixture. Some of the active ingredient’s components are
proteins, but others are not.
Ipsen’s criticism of the FDA’s explanation that a product
that is “analogous” to a protein must share its “critical
characteristics” is similarly reductive. By virtue of identifying
analogous products, the FDA demonstrates that it is possible
for an active ingredient to share a protein’s critical
characteristics, while also having other distinguishable
characteristics.
Second, Ipsen’s argument ultimately results in the violation
of a “basic principle of administrative law,” “courts must be
careful not to unduly second-guess an agency’s scientific
judgments.” Cytori Therapeutics, Inc., 715 F.3d at 923. “As
we have said, we review scientific judgments of the agency not
as the chemist, biologist, or statistician that we are qualified
neither by training nor experience to be, but as a reviewing
court exercising our narrowly defined duty of holding agencies
to certain minimal standards of rationality.” Troy Corp. v.
Browner, 120 F.3d 277, 283 (D.C. Cir. 1997) (cleaned up). But
Ipsen has not shown that the FDA acted unreasonably or
arbitrarily and capriciously in concluding that Somatuline
Depot was not analogous to a protein.

-- 18 of 20 --

19
Let’s follow Ipsen’s lead: an “analogous protein” includes
products that have less than forty amino acids so long as the
product is an alpha amino acid polymer with a specific, defined
sequence and is composed of multiple amino acid chains.
Not so. The FDA applies “analogous product” narrowly as
to proteins because there is a “lack of a precise-agreed upon
definition of ‘protein.’” J.A. 480. And as already stated, the
FDA has decided not to promulgate a rule defining an
analogous protein and, instead, will make case-by-case
determinations that “leave[] open the possibility that other
substances that [it] has not considered and directly addressed
could be analogous to a protein even if they are not themselves
proteins.” FDA Brief at 28. These were, at least in part,
scientific judgments. Notably, Ipsen does not argue the FDA’s
decision or approach conflicts with the ordinary meaning of
analogous.
Ipsen further argues that Somatuline Depot is analogous to
a protein because “the active ingredient lanreotide acetate
meets all of the definitional requirements of a protein” when it
is in “its finished dosage form—the one that is sold in
commerce and administered to patients.” Ipsen Brief at 40.
Once again, we find the FDA rejected Ipsen’s arguments
based on its scientific expertise. The FDA considered whether
the lanreotide nanotube assembly has structural and functional
characteristics that are “generally associated with proteins.”
J.A. 479–80. It ultimately concluded that the lanreotide
nanotube assembly fails on both fronts. Id. And the FDA
further explained that “the lanreotide nanotube assembly does
not have a specific biological function that is linked to its
structure.” J.A. 480. Ipsen does not argue that these
conclusions are not supported by substantial evidence or are
otherwise arbitrary and capricious. For the foregoing reasons,

-- 19 of 20 --

20
we affirm the District Court’s grant of summary judgment to
the FDA and InvaGen on this front.
So ordered.

-- 20 of 20 --