United States Code

EFFECTIVE DATE OF 1960 AMENDMENT Amendment of section by Pub. L. 86-618 effective, subject to the provisions of section 203 of Pub. L. 86-618, on July 12, 1960, see section 202 of Pub. L. 86-618, set out as a note under section 376 of this title.

STATE OR TERRITORIAL REQUIREMENTS Section 2 of Pub. L. 86-537 provided that: "Nothing in the amendments made by the first section of this Act [amending subsec. (k) and adding subsec. (1)] shall affect any requirement of the laws of any State or Territory."

§ 346. Tolerances for poisonous or deleterious substances in food; regulations.

Any poisonous or deleterious substance added to any food, except where such substance is required in the production thereof or cannot be avoided by good manufacturing practice shall be deemed to be unsafe for purposes of the application of clause (2) (A) of section 342 (a) of this title; but when such substance is so required or cannot be so avoided, the Secretary shall promulgate regulations limiting the quantity therein or thereon to such extend as he finds necessary for the protection of public health, and any quantity exceeding the limits so fixed shall also be deemed to be unsafe for purposes of the application of clause (2) (A) of section 342(a) of this title. While such a regulation is in effect limiting the quantity of any such substance in the case of any food, such food shall not, by reason of bearing or containing any added amount of such substance, be considered to be adulterated within the meaning of clause (1) of section 342 (a) of this title. In determining the quantity of such added substance to be tolerated in or on different articles of food the Secretary shall take into account the extent to which the use of such substance is required or cannot be avoided in the production of each such article, and the other ways in which the consumer may be affected by the same or other poisonous or deleterious substances. (As amended July 12, 1960, Pub. L. 86-618, title I, § 103(a) (1), 74 Stat. 398.)

AMENDMENTS

1960-Pub. L. 86-618 repealed former subsec. (b), which required the Secretary to promulgate regulations for the listing of coal-tar colors.

EFFECTIVE DATE OF 1960 AMENDMENT

Amendment of section by Pub. L. 86-618 effective, subject to the provisions of section 203 of Pub. L. 86618, on July 12, 1960, see section 202 of Pub. L. 86-618, set out as a note under section 376 of this title.

EFFECTIVE DATE OF NEMATOCIDE, PLANT REGULATOR, DEFOLIANT, And Desiccant AMENDMENT OF 1959 Effective date of subsec. (a) of this section as in force prior to July 22, 1954, with respect to particular commercial use of a nematocide, plant regulator, defoliant, or desiccant in or on a raw agricultural commodity made before Jan. 1, 1958, see section 3(b) of Pub. L. 86-139, Aug. 7, 1959, 73 Stat. 288, set out as a note under section 135 of Title 7, Agriculture.

§ 348. Food additives.

(3) No such regulation shall issue if a fair evaluation of the data before the Secretary

(A) fails to establish that the proposed use of the food additive, under the conditions of use to

be specified in the regulation, will be safe: Provided, That no additive shall be deemed to be safe if it is found to induce cancer when ingested by man or animal, or if it is found, after tests which are appropriate for the evaluation of the safety of food additives, to induce cancer in man or animal, except that this proviso shall not apply with respect to the use of a substance as an ingredient of feed for animals which are raised for food production, if the Secretary finds (i) that, under the conditions of use and feeding specified in proposed labeling and reasonably certain to be followed in practice, such additive will not adversely affect the animals for which such feed is intended, and (ii) that no residue of the additive will be found (by methods of examination prescribed or approved by the Secretary by regulations, which regulations shall not be subject to subsections (f) and (g) of this section) in any edible portion of such animal after slaughter or in any food yielded by or derived from the living animal;

(g) Judicial review.

(2) A copy of such petition shall be forthwith transmitted by the clerk of the court to the Secretary, or any officer designated by him for that purpose, and thereupon the Secretary shall file in the court the record of the proceedings on which he based his order, as provided in section 2112 of Title 28. Upon the filing of such petition the court shall have jurisdiction, which upon the filling of the record with it shall be exclusive, to affirm or set aside the order complained of in whole or in part. Until the filing of the record the Secretary may modify or set aside his order. The findings of the Secretary with respect to questions of fact shall be sustained if based upon a fair evaluation of the entire record at such hearing. The court shall advance on the docket and expedite the disposition of all causes filed therein pursuant to this section.

(As amended June 29, 1960, Pub. L. 86–546, § 2, 74 Stat. 255; Oct. 10, 1962, Pub. L. 87-781, title I, § 104(f) (1), 76 Stat. 785.)

AMENDMENTS

1962 Subsec. (c) (3) (A). Pub. L. 87-781 excepted the proviso from applying to use of a substance as an ingredient of feed for animals raised for food production, if under conditions of use specified in proposed labeling, and which conditions are reasonably certain to be followed in practice, such additive will not adversely affect the animals and no residue will be found in any edible portion of such animal after slaughter, or in any food from the living animal.

1960 Subsec. (g) (2). Pub. L. 86-546 substituted "forthwith transmitted by the clerk of the court to the Secretary, or any officer" for "served upon the Secretary, or upon any officer", "shall file in the court the record of the proceedings on which he based his order, as provided in section 2112 of Title 28" for "shall certify and file in the court a transcript of the proceedings and the record on which he based his order", and "Upon the filing of such petition the court shall have jurisdiction, which upon the filing of the record with it shall be exclusive," for "Upon such filing, the court shall have exclusive jurisdiction", and inserted sentence authorizing the Secretary to modify or set aside his order until the filing of the record.

EFFECTIVE DATE OF 1962 AMENDMENT; EXCEPTIONS Amendment of section by Pub. L. 87-781 effective on Oct. 10, 1962, see section 107 of Pub. L. 87-781, set out as a note under section 321 of this title.

SUBCHAPTER V.-DRUGS AND DEVICES

§ 351. Adulterated drugs and devices.

A drug or device shall be deemed to be adulterated

(a) Poisonous, insanitary, etc., ingredients; adequate controls in manufacture.

(1) If it consists in whole or in part of any filthy, putrid, or decomposed substance; or (2) (A) if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health; or (B) if it is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess; or (3) if it is a drug and its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health; or (4) if (A) it is a drug which bears or contains, for purposes of coloring only, a color additive which is unsafe within the meaning of section 376(a) of this title, or (B) it is a color additive the intended use of which in or on drugs is for purposes of coloring only and is unsafe within the meaning of section 376(a) of this title.

(As amended July 12, 1960, Pub. L. 86-618, title I, § 102(b) (1), 74 Stat. 398; Oct. 10, 1962, Pub. L. 87781, title I, § 101, 76 Stat. 780.)

AMENDMENTS

1962 Subsec. (a). Pub. L. 87-781 designated existing provisions of cl. (2) as (A) and added (B).

1960 Subsec. (a). Pub. L. 86-618 substituted provisions in cl. (4) relating to unsafe color additives for provisions which related to a coal-tar color other than one from a batch that has been certified in accordance with regulations as provided by section 354 of this title.

EFFECTIVE DATE OF 1962 AMENDMENT; EXCEPTIONS Amendment of section by Pub. L. 87-781 effective on the first day of the seventh calendar month following Oct. 1962, see section 107 of Pub. L. 87-781, set out as a note under section 321 of this title.

§ 352. Misbranded drugs and devices.

A drug or device shall be deemed to be misbranded

(e) Designation of drug by established name; quantity of ingredients; labeling requirements; "established name" defined.

(1) If it is a drug, unless (A) its label bears, to the exclusion of any other nonproprietary name

(except the applicable systematic chemical name or the chemical formula), (i) the established name (as defined in paragraph (2) of this subsection) of the drug, if such there be, and (ii), in case it is fabricated from two or more ingredients, the established name and quantity of each active ingredient, including the quantity, kind, and proportion of any alcohol, and also including, whether active or not, the established name and quantity or proportion of any bromides, ether, chloroform, acetanilid, acetphenetidin, amidopyrine, antipyrine, atropine, hyoscine, hyoscyamine, arsenic, digitalis, digitalis glucosides, mercury, ouabain, strophanthin, strychnine, thyroid, or any derivative or preparation of any such substances, contained therein: Provided, That the requirement for stating the quantity of the active ingredients, other than the quantity of those specifically named in this subsection, shall apply only to prescription drugs; and (B) for any prescription drug the established name of such drug or ingredient, as the case may be, on such label (and on any labeling on which a name for such drug or ingredient is used) is printed prominently and in type at least half as large as that used thereon for any proprietary name or designation for such drug or ingredient: Provided, That to the extent that compliance with the requirements of clause (A) (ii) or clause (B) of this subsection is impracticable, exemptions shall be established by regulations promulgated by the Secretary.

(2) As used in this subsection (e), the term "established name", with respect to a drug or ingredient thereof, means (A) the applicable official name designated pursuant to section 358 of this title, or (B), if there is no such name and such drug, or such ingredient, is an article recognized in an official compendium, then the official title thereof in such compendium, or (C) if neither clause (A) nor clause (B) of this paragraph applies, then the common or usual name, if any, of such drug or of such ingredient: Provided further, That where clause (B) of this paragraph applies to an article recognized in the United States Pharmacopeia and in the Homoeopathic Pharmacopoeia under different official titles, the official title used in the United States Pharmacopeia shall apply unless it is labeled and offered for sale as a homoeopathic drug, in which case the official title used in the Homoeopathic Pharmacopoeia shall apply.

(g) Representations as recognized drug; packing and labeling; inconsistent requirements for designation of drug.

If it purports to be a drug the name of which is recognized in an official compendium, unless it is packaged and labeled as prescribed therein: Provided, That the method of packing may be modified with the consent of the Secretary. Whenever a drug is recognized in both the United States Pharmacopoeia and the Homeopathic Pharmacopoeia of the United States, it shall be subject to the requirements of the United States Pharmacopeia with respect to packaging and labeling unless it is labeled and offered for sale as a homeopathic drug, in which case it shall be subject to the provisions of the

Homœopathic Pharmacopoeia of the United States, and not those of the United States Pharmacopoeia: Provided further, That, in the event of inconsistency between the requirements of this subsection and those of subsection (e) of this section as to the name by which the drug or its ingredients shall be designated, the requirements of subsection (e) of this section shall prevail.

(1) Antibiotic drugs improperly certified.

If it is, or purports to be, or is represented as a drug composed wholly or partly of any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any other antibiotic drug, or any derivative thereof, unless (1) it is from a batch with respect to which a certificate or release has been issued pursuant to section 357 of this title, and (2) such certificate or release is in effect with respect to such drug: Provided, That this subsection shall not apply to any drug or class of drugs exempted by regulations promulgated under section 357 (c) or (d) of this title.

(m) Color additives; packing and labeling.

If it is a color additive the intended use of which in or on drugs is for the purpose of coloring only, unless its packaging and labeling are in conformity with such packaging and labeling requirements applicable to such color additive, as may be contained in regulations issued under section 376 of this title. (n) Prescription drug advertisements; established name; quantitative formula; side effects, contraindications, and effectiveness; prior approval; false advertising; labeling.

In the case of any prescription drug distributed or offered for sale in any State, unless the manufacturer, packer, or distributor thereof includes in all advertisements and other descriptive printed matter issued or caused to be issued by the manufacturer, packer, or distributor with respect to that drug a true statement of (1) the established name as defined in subsection (e) of this section, printed prominently and in type at least half as large as that used for any trade or brand name thereof, (2) the form. ula showing quantitatively each ingredient of such drug to the extent required for labels under subsection (e) of this section, and (3) such other information in brief summary relating to side effects, contraindications, and effectiveness as shall be required in regulations which shall be issued by the Secretary in accordance with the procedure specified in section 371(e) of this title: Provided, That (A) except in extraordinary circumstances, no regulation issued under this subsection shall require prior approval by the Secretary of the content of any advertisement, and (B) no advertisement of a prescription drug, published after the effective date of regulatons issued under this subsection applicable to advertisements of prescription drugs, shall with respect to the matters specified in this subsection or covered by such regulations, be subject to the provisions of sections 52-57 of Title 15. This subsection (n) shall not be applicable to any printed matter which the Secretary determines to be labeling as defined in section 321 (m) of this title.

(0) Drugs from nonregistered establishments.

If it is a drug and was manufactured, prepared, propagated, compounded, or processed in an establishment in any State not duly registered under section 360 of this title. (As amended July 12, 1960, Pub. L. 86-618, title I, § 102(b) (2), 74 Stat. 398; Oct. 10, 1962, Pub. L. 87-781, title I, §§ 105(c), 112 (a), (b), 131(a), title III, § 305, 76 Stat. 785, 790, 791, 795.)

AMENDMENTS

1962 Subsec. (e). Pub. L. 87–781, § 112(a), designated existing provisions as par. (1), substituted ", unless (A) its label bears, to the exclusion of any other nonproprietary name (except the applicable systematic chemical name or the chemical formula), (1) the established name (as defined in par. (2) of this subsection) of the drug, if such there be, and (ii), in case it is fabricated from two or more ingredients, the established name and quantity" for "and is not designated solely by a name recognized in an official compendium unless its label bears (1) the common or usual name of the drug, if such there be; and (2), in case it is fabricated from two or more ingredients, the common or usual name", and "the established name" for "the name", provided that the requirement for stating the quantity of active ingredients, other than those specified in this subsection, applies only to prescription drugs, and that the established name of a drug on a label is to be printed prominently and in type at least half as large as used for any proprietary designation, and added par. (2) defining "established name."

Subsec. (g). Pub. L. 87-781, § 112(b), provided that if there is an inconsistency between the provisions of this subsection and those of subsec. (e) of this section, as to the name of a drug, the requirements of subsec. (e) should prevail.

Subsec. (1). Pub. L. 87-781, § 105(c), substituted "bacitracin, or any other antibiotic drug" for "or bacitracin." Subsec. (n). Pub. L. 87-781, § 131(a), added subsec. (n).

Subsec. (o). Pub. L. 87-781, § 305, added subsec. (o). 1960 Subsec. (m). Pub. L. 86–618 added subsec, (m). EFFECTIVE DATE OF 1962 AMENDMENT

Section 112(c) of Pub. L. 87-781 provided that: "This section [amending subsecs. (e) and (g) of this section] shall take effect on the first day of the seventh calendar month following the month in which this Act is enacted [Oct. 1962]."

Section 131(b) of Pub. L. 87-781 provided that: "No drug which was being commercially distributed prior to the date of enactment of this Act [Oct. 10, 1962] shall be deemed to be misbranded under paragraph (n) of section 502 of the Federal Food, Drug, and Cosmetic Act [subsec. (n) of this section], as added by this section, until the earlier of the following dates: (1) the first day of the seventh month following the month in which this Act is enacted; or (2) the effective date of regulations first issued under clause (3) of such paragraph (n) in accordance with the procedure specified in section 701(e) of the Federal Food, Drug, and Cosmetic Act [section 371(e) of this title]."

Amendment of section by Pub. L. 87-781 effective on the first day of the seventh calendar month following Oct. 1962, see section 107 of Pub. L. 87-781, set out as a note under section 321 of this title.

§ 353. Exemptions in case of drugs and devices.

(b) Prescription by physician; exemption from labeling and prescription requirements; misbranded drugs; compliance with narcotic and marihuana laws.

(1) A drug intended for use by man which—

(C) is limited by an approved application under section 355 of this title to use under the professional supervision of a practitioner licensed by law to administer such drug,

shall be dispensed only (i) upon a written prescription of a practitioner licensed by law to administer such drug, or (ii) upon an oral prescription of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral prescription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writing and filed by the pharmacist. The act of dispensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which results in the drug being misbranded while held for sale.

(As amended Oct. 10, 1962, Pub. L. 87-781, title I, § 104(e) (2), 76 Stat. 785.)

AMENDMENTS

1962 Subsec. (b)(1) (C). Pub. L. 87-781, substituted "approved" for "effective."

EFFECTIVE Date of 1962 Amendment; EXCEPTIONS Amendment of section by Pub. L. 87-781 effective on Oct. 10, 1962, see section 107 of Pub. L. 87-781, set out as a note under section 321 of this title.

§ 354. Repealed. Pub. L. 86-618, title I, § 103(a)(2), July 12, 1960, 74 Stat. 398.

Section, act June 25, 1938, ch. 675, § 504, 52 Stat. 1052, required the Secretary to promulgate regulations for the listing of coal-tar colors.

EFFECTIVE DATE OF REPEAL

Repeal of section effective, subject to the provisions of section 203 of Pub. L. 86-618, on July 12, 1960, see section 202 of Pub. L. 86-618, set out as a note under section 376 of this title.

§ 355. New drugs.

(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.

(b) Filing application; contents.

Any person may file with the Secretary an application with respect to any drug subject to the provisions of subsection (a) of this section. Such person shall submit to the Secretary as a part of the application (1) full reports of investigations which have been made to show whether or not such drug is safe for use and whether such drug is effective in use; (2) a full list of the articles used as components of such drug; (3) a full statement of the composition of such drug; (4) a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug; (5) such samples of such drug and of the articles used as components thereof as the Secretary may require; and (6) specimens of the labeling proposed to be used for such drug.

Within one hundred and eighty days after the filing of an application under this subsection, or such

additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either

(1) approve the application if he then finds that none of the grounds for denying approval specified in subsection (d) of this section applies,

(2) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d) of this section on the question whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs.

(d) Grounds for refusing application; approval of application; "substantial evidence" defined.

If the Secretary finds, after due notice to the applicant in accordance with subsection (c) of this section and giving him an opportunity for a hearing, in accordance with said subsection, that (1) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b) of this section, do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof; (2) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions; (3) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity; (4) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions; or (5) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof; or (6) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; he shall issue an order refusing to approve the application. after such notice and opportunity for hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an order approving the application. As used in this subsection and subsection (e) of this section, the term "substantial evidence" means evidence consisting of adequate and wellcontrolled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly

If,

and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.

(e) Withdrawal of approval; grounds; immediate suspension upon finding imminent hazard to public health.

The Secretary shall, after due notice and opportunity for hearing to the applicant, withdraw approval of an application with respect to any drug under this section if the Secretary finds (1) that clinical or other experience, tests, or other scientific data show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved; (2) that new evidence of clinical experience, not contained in such application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved; or (3) on the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling thereof; or (4) that the application contains any untrue statement of a material fact: Provided, That if the Secretary (or in his absence the officer acting as Secretary) finds that there is an imminent hazard to the public health, he may suspend the approval of such application immediately, and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing under this subsection; but the authority conferred by this proviso to suspend the approval of an application shall not be delegated. The Secretary may also, after due notice and opportunity for hearing to the applicant, withdraw the approval of an application with respect to any drug under this section if the Secretary finds (1) that the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports, in accordance with a regulation or order under subsection (j) of this section, or the applicant has refused to permit access to, or copying or verification of, such records as required by paragraph (2) of such subsection; or (2) that on the basis of new information before him, evaluated together with the evidence before him when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of; or (3) that on the basis of new information before him, evaluated to

gether with the evidence before him when the application was approved, the labeling of such drug. based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice from the Secretary specifying the matter complained of. Any order under this subsection shall state the findings upon which it is based.

(f) Revocation of order refusing, withdrawing or suspending approval of application.

Whenever the Secretary finds that the facts so require, he shall revoke any previous order under subsection (d) or (e) of this section refusing, withdrawing, or suspending approval of an application and shall approve such application or reinstate such approval, as may be appropriate.

(g) Service of orders.

Orders of the Secretary issued under this section shall be served (1) in person by any officer or employee of the Department designated by the Secretary or (2) by mailing the order by registered mail or by certified mail addressed to the applicant or respondent at his last-known address in the records of the Secretary.

(h) Appeal from order.

An appeal may be taken by the applicant from an order of the Secretary refusing or withdrawing approval of an application under this section. Such appeal shall be taken by filing in the United States court of appeals for the circuit wherein such applicant resides or has his principal place of business, or in the United States Court of Appeals for the District of Columbia Circuit, within sixty days after the entry of such order, a written petition praying that the order of the Secretary be set aside. A copy

of such petition shall be forthwith transmitted by the clerk of the court to the Secretary, or any officer designated by him for that purpose, and thereupon the Secretary shall certify and file in the court the record upon which the order complained of was entered, as provided in section 2112 of Title 28. Upon the filing of such petition such court shall have exclusive jurisdiction to affirm or set aside such order, except that until the filing of the record the Secretary may modify or set aside his order. No objection to the order of the Secretary shall be considered by the court unless such objection shall have been urged before the Secretary or unless there were reasonable grounds for failure so to do. The finding of the Secretary as to the facts, if supported by substantial evidence, shall be conclusive. If any person shall apply to the court for leave to adduce additional evidence, and shall show to the satisfaction of the court that such additional evidence is material and that there were reasonable grounds for failure to adduce such evidence in the proceeding before the Secretary, the court may order such additional evidence to be taken before the Secretary and to be adduced upon the hearing in such manner and upon such terms and conditions as to the court may seem proper. The Secretary may modify his findings as to the facts by reason of the additional evidence so taken, and he shall file with the court such modified findings which, if supported by substantial evi

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