Ipsen Biopharmaceuticals, Inc. v. Xavier Becerra (REISSUED PUBLIC OPINION)

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

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.

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.

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

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

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.

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

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.”).

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

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

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:

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.”

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.

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

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

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

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

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.

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,

20

we affirm the District Court’s grant of summary judgment to

the FDA and InvaGen on this front.

So ordered.