The Federal Food, Drug, and Cosmetic Act (Act) prohibits the
marketing of a "new drug" without the prior approval of the Food
and Drug Administration (FDA). Section 201(p) of the Act defines a
"new drug" as
"any drug . . . [which] is not generally recognized . . . as
safe and effective . . . or . . . which has not, otherwise than in
[safety and effectiveness] investigations, been used to a material
extent or for a material time."
Section 201(g)(1) defines the term "drug" as,
inter
alia, "articles intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man or in other
animals." The Government brought an action in Federal District
Court to enjoin respondent Generix Drug Corp. (respondent) from
distributing a number of generic drug products containing specified
active ingredients, alleging that the FDA had never approved "new
drug" applications with respect to such products. Holding that a
generic drug product containing the same active ingredients as a
previously approved pioneer drug marketed under a brand name is a
"new drug" if there is a reasonable possibility that the
differences in inactive "excipients" between the generic product
and the pioneer drug will make the generic product less safe and
effective, and finding that the Government had established a
reasonable possibility that the safety and effectiveness of
respondent's generic drug products might be affected by differences
between their inactive "excipients" and those found in approved
products, the court enjoined respondent from distributing the
products in question. The Court of Appeals vacated the injunction
and remanded with instructions to dismiss the complaint, holding
that the statutory prohibition against the sale of a "new drug"
without prior FDA approval does not apply to a drug product having
the same active ingredients as a previously approved drug product,
regardless of any differences in "excipients."
Held: A generic product is a "drug" within the meaning
of the indicated definition in § 201(g)(1). That definition is
broad enough to encompass entire drug products, complete with their
active and inactive ingredients. Accordingly, a generic drug
product is a "new drug," subject to prior FDA approval, until the
product (and not merely its active ingredients) no longer falls
within the terms of § 201(p). Pp.
460 U. S.
457-461.
654 F.2d 1114, reversed.
STEVENS, J., delivered the opinion for a unanimous Court.
Page 460 U. S. 454
JUSTICE STEVENS delivered the opinion of the Court.
The question presented is whether the statutory prohibition
against the marketing of a "new drug" without the prior approval of
the Food and Drug Administration (FDA) requires respondent Generix
Drug Corp. to have approved new drug applications (NDA's) before it
may market its generic drug products. In statutory terms, we are
required to determine whether the term "drug," as used in the
relevant sections of the Federal Food, Drug, and Cosmetic Act
(Act), as amended, 21 U.S.C. § 301
et seq. (1976 ed. and
Supp V), refers only to the active ingredient in a drug product or
to the entire product. We hold that Congress intended the word to
have the broader meaning.
I
The active ingredients in most prescription drugs constitute
less than 10% of the product; inactive "excipients" (such as
coatings, binders, and capsules) constitute the rest. The term
"generic drug" is used to describe a product that contains the same
active ingredients, but not necessarily the same excipients, as a
so-called "pioneer drug" that is marketed
Page 460 U. S. 455
under a brand name. [
Footnote
1] Respondent Generix is a distributor of generic drugs
manufactured by other firms.
The Government initiated this action to enjoin Generix from
distributing in interstate commerce a number of generic drug
products that contain eight specified active ingredients. [
Footnote 2] It alleged that the FDA had
never approved new drug applications with respect to any of those
products. [
Footnote 3]
The District Court held that a generic drug product containing
the same active ingredients as a previously approved pioneer drug
is a "new drug," requiring an NDA, only if there is a reasonable
possibility that the differences in excipients between the generic
product and the pioneer will make the generic product less safe and
effective.
498 F.
Supp. 288, 292. The court found clear evidence in support of
the general proposition that differences in excipients may affect
the safety and effectiveness of drug products. Excipients may
affect the rate at which the active ingredient is delivered to a
diseased organ. If delivery is too fast, the patient may be harmed
just as if he received an overdose; if delivery is too slow, the
treatment of the disease may be ineffective.
Id. at
291.
Page 460 U. S. 456
In this case, the District Court found that the Government had
established a reasonable possibility that the safety and
effectiveness of six of respondent's generic drug products might be
affected by differences between their excipients and those found in
approved products. [
Footnote 4]
Accordingly, it enjoined the defendants from further distribution
of products containing the designated active ingredients.
The Court of Appeals for the Fifth Circuit, now the Eleventh
Circuit, vacated the District Court's injunction and remanded with
instructions to dismiss the complaint. 654 F.2d 1114. It held that
the statutory prohibition against the sale of a "new drug" without
prior approval does not apply to a drug product having the same
active ingredients as a previously approved drug product,
regardless of any differences in excipients. It based that
conclusion on its view that the statutory requirement of evaluating
the safety and effectiveness of new drugs must normally relate to
active ingredients, because the precise technique of formulating
the finished drug is not part of the information generally known to
the medical or scientific community. Moreover, it believed that the
legislative history suggested that Congress had not intended to
create a product-by-product licensing system. Since the active
ingredients at issue had all received the necessary approval, the
Court of Appeals concluded that the Government was entitled to no
relief at all.
Because the question is obviously important, and because it has
been decided differently in other Circuits, [
Footnote 5] we granted certiorari. 455 U.S. 988.
[
Footnote 6]
Page 460 U. S. 457
II
In resolving the narrow issue presented, the Court of Appeals
misread the statutory text.
Section 201(p) of the Act defines a "new drug" to be
"any drug . . . [which] is not generally recognized . . . as
safe and effective . . . or . . . which has not, otherwise than in
[safety and effectiveness] investigations, been used to a material
extent or for a material time. . . . [
Footnote 7]"
The Court of Appeals did not rest its decision on a finding that
Generix's products are generally recognized as safe and effective;
rather, its conclusion rested on the proposition that the statutory
phrase "any drug" does not include a complete drug product, but
only an active ingredient. That proposition is simply
untenable.
The original Federal Food and Drugs Act of June 30, 1906, 34
Stat. 768, prohibited the sale of adulterated or misbranded
Page 460 U. S. 458
foods or drugs. The definition of the term "drug" in that
statute was plainly broad enough to describe a completed drug
product. It provided:
"That the term 'drug,' as used in this Act, shall include all
medicines and preparations recognized in the United States
Pharmacopoeia or National Formulary for internal or external use,
and any substance or mixture of substances intended to be used for
the cure, mitigation, or prevention of disease of either man or
other animals."
34 Stat. 769.
In 1938, Congress passed the new statute, which requires that an
application be submitted to the FDA before any "new drug" may be
introduced into interstate commerce. Federal Food, Drug, and
Cosmetic Act of 1938, 52 Stat. 1040, 21 U.S.C. § 301
et
seq. (1976 ed. and Supp. V). The new Act's definition of the
term "drug" is even broader than the old one:
"[201](g)(1) The term 'drug' means (A) articles recognized in
the official United States Pharmacopoeia, official Homoeopathic
Pharmacopoeia of the United States, or official National Formulary,
or any supplement to any of them; and (B) articles intended for use
in the diagnosis, cure, mitigation, treatment, or prevention of
disease in man or other animals; and (C) articles (other than food)
intended to affect the structure or any function of the body of man
or other animals; and (D) articles intended for use as a component
of any article specified in clauses (A), (B), or (C) of this
paragraph; but does not include devices or their components, parts,
or accessories."
52 Stat. 1041, as amended, and as set forth in 21 U.S.C. §
321(g)(1).
In examining this statutory definition, the Court of Appeals was
persuaded that only active ingredients come within the terms of
subsection (A). 654 F.2d at 1116. [
Footnote 8] Unfortunately,
Page 460 U. S. 459
the court did not analyze the entire definition. If it had done
so, it would have noted both that the terms of subsections (A),
(B), and (C) are plainly broad enough to include more than just
active ingredients, and that they
must do so unless
subsection (D) is to be superfluous. Because the definition is
disjunctive, generic drug products are quite plainly drugs within
the meaning of the Act.
The natural reading of this definition is corroborated by other
sections of the Act. Section 501(a) provides that a "drug" is
deemed adulterated "if [it is a drug which] bears or contains, for
purposes of coloring only, a color additive which is unsafe." 52
Stat. 1049, as amended, 21 U.S.C. § 351(a)(4). Section 502(e)
provides that a "drug . . . fabricated from two or more
ingredients" shall be deemed to be misbranded unless its label
includes, "whether active or not, the established name and quantity
or proportion of any bromides, ether, chloroform, [etc.]." 52 Stat.
1050-1051, as amended, 21 U.S.C. § 352(e)(1). And § 505(b) requires
that an application for new drug approval contain "a full list of
the articles used as components.of such drug [and] a full statement
of the composition of such drug." 52 Stat. 1052, 21 U.S.C. §
355(b). The term "drug" is plainly intended throughout the Act to
include entire drug products, complete with active and inactive
ingredients. [
Footnote 9]
Neither the Court of Appeals nor respondents have pointed to
anything in the text of the Act that is inconsistent
Page 460 U. S. 460
with our reading of its plain language. [
Footnote 10] The respondents make a number of
arguments based upon legislative history and administrative
practice regarding the marketing of generic prescription and
over-the-counter drugs that lend support to the proposition that
two products need not have precisely the same molecular structure
in order to be the same "drug." [
Footnote 11] None of those arguments, however, warrants
the conclusion that the term "drug" means only the active
ingredient in a product.
In this case, we are not required to determine what types of
differences between drugs would be significant or insignificant
under the statute. Respondent Generix argues only
Page 460 U. S. 461
that its products are not new drugs under the theory that "drug"
means "active ingredient"; it does not argue that its complete
products -- active ingredients and excipients together -- are the
same as previously approved products. The latter argument would, of
course, have been unavailing on the facts before us, for the
respondent has not questioned the District Court's finding of a
reasonable possibility that its products are not bioequivalent to
any previously approved products. [
Footnote 12] We thus do not reach the issue of whether
two demonstrably bioequivalent products, containing the same active
ingredients but different excipients, might under some
circumstances be the same "drug."
In summary, a generic drug product is a "drug" within the
meaning of § 201(g)(1) of the Act. Such a product is therefore a
"new drug," subject to the requirements of § 505, until the product
(and not merely its active ingredient) no longer falls within the
terms of § 201(p). The judgment of the Court of Appeals is
accordingly
Reversed.
[
Footnote 1]
Generic drugs, also called "copycat" or "me-too" drugs, are
usually marketed at relatively low prices because their
manufacturers do not incur the research, development, and
promotional costs normally associated with the creation and
marketing of an original product.
[
Footnote 2]
The eight ingredients were: allopurinol, spironolactone with
hydrochlorothiazide, furosemide, diethylpropion hydrochloride,
chlorothiazide with reserpine, amitriptyline with perphenazine,
prochlorperazine maleate, and chlorthalidone. The District Court
explained the use of each of these ingredients, noting that
furosemide is one of the most widely used drugs in the United
States, it being used to treat hypertension and edema.
498 F.
Supp. 288, 289-290.
[
Footnote 3]
Section 505(a) of the Act, 52 Stat. 1052, as amended, 76 Stat.
784, 21 U.S.C. § 355(a), provides:
"(a) Necessity of effective approval of application"
"No person shall introduce or deliver for introduction into
interstate commerce any new drug, unless an approval of an
application filed pursuant to subsection (b) of this section is
effective with respect to such drug."
[
Footnote 4]
Since no evidence concerning the safety and effectiveness of
formulations containing prochlorperazine maleate or chlorthalidone
was presented at the hearing, no relief was granted with respect to
products containing those ingredients. 498 F. Supp. at 294.
[
Footnote 5]
Premo Pharmaceutical Laboratories, Inc. v. United
States, 629 F.2d 795 (CA2 1980).
[
Footnote 6]
Respondent Generix has argued that the case is moot because
almost its entire store of products containing the disputed active
ingredients is no longer salable, and in the future it intends only
to sell generic drugs that have FDA approval. The possibility that
respondent may change its mind in the future is sufficient to
preclude a finding of mootness.
See City of Mesquite v.
Aladdin's Castle, Inc., 455 U. S. 283,
455 U. S.
288-289 (1982);
United State v. W. T. Grant
Co., 345 U. S. 629,
345 U. S. 632
(1953).
[
Footnote 7]
The full text of § 201(p), 52 Stat. 1041-1042, as amended, 76
Stat. 781, 21 U.S.C. 321(p), reads as follows:
"The term 'new drug' means -- "
"(1) Any drug (except a new animal drug or an animal feed
bearing or containing a new animal drug) the composition of which
is such that such drug is not generally recognized, among experts
qualified by scientific training and experience to evaluate the
safety and effectiveness of drugs, as safe and effective for use
under the conditions prescribed, recommended, or suggested in the
labeling thereof, except that such a drug not so recognized shall
not be deemed to be a 'new drug' if at any time prior to June 25,
1938, it was subject to the Food and Drugs Act of June 30, 1906, as
amended, and if at such time its labeling contained the same
representations concerning the conditions of its use; or"
"(2) Any drug (except a new animal drug or an animal feed
bearing or containing a new animal drug) the composition of which
is such that such drug, as a result of investigations to determine
its safety and effectiveness for use under such conditions, has
become so recognized, but which has not, otherwise than in such
investigations, been used to a material extent or for a material
time under such conditions."
[
Footnote 8]
But cf. The United States Pharmacopeia 2 (20th rev.
ed.1980) ("article" is an item for which a monograph exists;
monographs may exist for the "finished, or partially finished . . .
preparation or product of one or more official substances [active
ingredients or excipients] formulated for use on or for the
patient").
[
Footnote 9]
At oral argument, respondents suggested that it would be
nonsensical to understand the word "drug" in § 502(i) of the Act,
52 Stat. 1051, 21 U.S.C. § 352(i), to mean "drug product," because
any generic drug is "an imitation of another drug." Tr. of Oral
Arg. 41-42. But § 502(i) is intended to prohibit a company from
passing an imitation off as the original; if "imitation" is
understood with that in mind, it becomes apparent that the word
"drug" can and should mean "drug product" in § 502(i), as well.
[
Footnote 10]
Both the respondents and the Court of Appeals have suggested
that, if the term "new drug" referred to complete drug products, as
opposed to active ingredients, then § 201(p)(2) of the Act would be
superfluous.
See 654 F.2d at 1116-1117. That section (set
forth in
n 7,
supra)
establishes that, before a drug may drop out of regulation, it must
-- in addition to being generally recognized among experts as safe
and effective for the prescribed use -- have been used to a
material extent or for a material time other than in scientific
investigations. The argument appears to rest on the premise that
the only regulatory burden associated with being a new drug is the
need to file a new drug application. Since an application must be
filed
before a drug can receive general public use, the
argument is that nothing would be gained by deregulation, because
the only regulatory burden would have been sustained before one
could be exempted from that burden. But the premise is flawed.
Significant recordkeeping and reporting burdens are lifted when the
"new drug" status terminates.
See § 505(j) of the Act, 76
Stat. 782-783, 21 U.S.C. § 355(j).
See also 21 CFR §§
310.300-310.303 (1982).
[
Footnote 11]
They argue (1) that legislative history suggests that the 1938
Congress rejected a product-by-product licensing system, (2) that,
in 1938, many pharmacists compounded heir own pills with excipients
of their choice, and were not expected to file NDA's for each pill
or every time they used a new excipient, (3) that, between 1938 and
1968, the FDA advised drug manufacturers that certain generic
products were not "new drugs," and therefore did not require NDA's
to be marketed, (4) that the 1962 amendments reveal a congressional
interest in promoting the availability of generic drugs in order to
reduce the price of prescription drugs for consumers, (5) that, in
applying the 1962 amendments, the FDA took the position that, for
some purposes, generic drug products were covered by NDA's of the
pioneer drugs that they copied, and (6) that since 1972 the FDA has
used a "monograph" system to permit the marketing of
over-the-counter drugs that meet prescribed standards and contain
"suitable" excipients.
[
Footnote 12]
Because the Government did not cross-appeal from the District
Court's refusal to grant relief as to products containing
prochlorperazine maleate and chlorthalidone,
see n 4,
supra, we have no
occasion to pass on the District Court's conclusion that the FDA
has the burden of showing a "reasonable possibility" that a drug
product is not bioequivalent to an approved product in order to
enjoin distribution.