21 U.S.C. § 353 — Exemptions and consideration for certain

Page 167 TITLE 21—FOOD AND DRUGS § 353 COUNTERFEITING OF DRUGS; CONGRESSIONAL FINDINGS AND DECLARATION OF POLICY Pub. L. 89–74, § 9(a), July 15, 1965, 79 Stat. 234, provided that: ‘‘The Congress finds and declares that there is a substantial traffic in counterfeit drugs simulating the brand or other identifying mark or device of the manu- facturer of the genuine article; that such traffic poses a serious hazard to the health of innocent consumers of such drugs because of the lack of proper qualifications, facilities, and manufacturing controls on the part of the counterfeiter, whose operations are clandestine; that, while such drugs are deemed misbranded within the meaning of section 502(i) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 352(i)], the controls for the suppression of the traffic in such drugs are inadequate because of the difficulty of determining the place of interstate origin of such drugs and, if that place is dis- covered, the fact that the implements for counter- feiting are not subject to seizure, and that these factors require enactment of additional controls with respect to such drugs without regard to their interstate or intrastate origins.’’ Provisions as effective Feb. 1, 1966, see section 11 of Pub. L. 89–74, set out as an Effective Date of 1965 Amendment note under section 321 of this title. Executive Documents TRANSFER OF FUNCTIONS For transfer of functions of Federal Security Admin- istrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see notes set out under section 321 of this title. § 353. Exemptions and consideration for certain drugs, devices, and biological products (a) Regulations for goods to be processed, la- beled, or repacked elsewhere The Secretary is directed to promulgate regu- lations exempting from any labeling or pack- aging requirement of this chapter drugs and de- vices which are, in accordance with the practice of the trade, to be processed, labeled, or re- packed in substantial quantities at establish- ments other than those where originally proc- essed or packed, on condition that such drugs and devices are not adulterated or misbranded under the provisions of this chapter upon re- moval from such processing, labeling, or repack- ing establishment. (b) Prescription by physician; exemption from la- beling and prescription requirements; mis- branded drugs; compliance with narcotic and marihuana laws (1) A drug intended for use by man which— (A) because of its toxicity or other poten- tiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the su- pervision of a practitioner licensed by law to administer such drug; or (B) is limited by an approved application under section 355 of this title to use under the professional supervision of a practitioner li- censed by law to administer such drug; shall be dispensed only (i) upon a written pre- scription of a practitioner licensed by law to ad- minister such drug, or (ii) upon an oral prescrip- tion of such practitioner which is reduced promptly to writing and filed by the pharmacist, or (iii) by refilling any such written or oral pre- scription if such refilling is authorized by the prescriber either in the original prescription or by oral order which is reduced promptly to writ- ing and filed by the pharmacist. The act of dis- pensing a drug contrary to the provisions of this paragraph shall be deemed to be an act which re- sults in the drug being misbranded while held for sale. (2) Any drug dispensed by filling or refilling a written or oral prescription of a practitioner li- censed by law to administer such drug shall be exempt from the requirements of section 352 of this title, except paragraphs (a), (i)(2) and (3), (k), and (l), and the packaging requirements of paragraphs (g), (h), and (p), if the drug bears a label containing the name and address of the dispenser, the serial number and date of the pre- scription or of its filling, the name of the pre- scriber, and, if stated in the prescription, the name of the patient, and the directions for use and cautionary statements, if any, contained in such prescription. This exemption shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursu- ant to diagnosis by mail, or to a drug dispensed in violation of paragraph (1) of this subsection. (3) The Secretary may by regulation remove drugs subject to section 355 of this title from the requirements of paragraph (1) of this subsection when such requirements are not necessary for the protection of the public health. (4)(A) A drug that is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing the label of the drug fails to bear, at a minimum, the symbol ‘‘Rx only’’. (B) A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing the label of the drug bears the symbol described in subparagraph (A). (5) Nothing in this subsection shall be con- strued to relieve any person from any require- ment prescribed by or under authority of law with respect to drugs now included or which may hereafter be included within the classifica- tions stated in sections 4721, 6001, and 6151 of title 26, or to marihuana as defined in section 4761 of title 26. (c) Sales restrictions (1) No person may sell, purchase, or trade or offer to sell, purchase, or trade any drug sample. For purposes of this paragraph and subsection (d), the term ‘‘drug sample’’ means a unit of a drug, subject to subsection (b), which is not in- tended to be sold and is intended to promote the sale of the drug. Nothing in this paragraph shall subject an officer or executive of a drug manu- facturer or distributor to criminal liability sole- ly because of a sale, purchase, trade, or offer to sell, purchase, or trade in violation of this para- graph by other employees of the manufacturer or distributor. (2) No person may sell, purchase, or trade, offer to sell, purchase, or trade, or counterfeit any coupon. For purposes of this paragraph, the term ‘‘coupon’’ means a form which may be re- deemed, at no cost or at a reduced cost, for a drug which is prescribed in accordance with sub- section (b). (3)(A) No person may sell, purchase, or trade, or offer to sell, purchase, or trade, any drug— Page 168 TITLE 21—FOOD AND DRUGS § 353 (i) which is subject to subsection (b), and (ii)(I) which was purchased by a public or private hospital or other health care entity, or (II) which was donated or supplied at a re- duced price to a charitable organization de- scribed in section 501(c)(3) of title 26. (B) Subparagraph (A) does not apply to— (i) the purchase or other acquisition by a hospital or other health care entity which is a member of a group purchasing organization of a drug for its own use from the group pur- chasing organization or from other hospitals or health care entities which are members of such organization, (ii) the sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug by an organization described in subparagraph (A)(ii)(II) to a nonprofit affiliate of the organi- zation to the extent otherwise permitted by law, (iii) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug among hospitals or other health care entities which are under common control, (iv) a sale, purchase, or trade of a drug or an offer to sell, purchase, or trade a drug for emergency medical reasons, or (v) a sale, purchase, or trade of a drug, an offer to sell, purchase, or trade a drug, or the dispensing of a drug pursuant to a prescription executed in accordance with subsection (b). For purposes of this paragraph, the term ‘‘enti- ty’’ does not include a wholesale distributor of drugs or a retail pharmacy licensed under State law and the term ‘‘emergency medical reasons’’ includes transfers of a drug between health care entities or from a health care entity to a retail pharmacy undertaken to alleviate temporary shortages of the drug arising from delays in or interruptions of regular distribution schedules. (d) Distribution of drug samples (1) Except as provided in paragraphs (2) and (3), no person may distribute any drug sample. For purposes of this subsection, the term ‘‘dis- tribute’’ does not include the providing of a drug sample to a patient by a— (A) practitioner licensed to prescribe such drug, (B) health care professional acting at the di- rection and under the supervision of such a practitioner, or (C) pharmacy of a hospital or of another health care entity that is acting at the direc- tion of such a practitioner and that received such sample pursuant to paragraph (2) or (3). (2)(A) The manufacturer or authorized dis- tributor of record of a drug subject to subsection (b) may, in accordance with this paragraph, dis- tribute drug samples by mail or common carrier to practitioners licensed to prescribe such drugs or, at the request of a licensed practitioner, to pharmacies of hospitals or other health care en- tities. Such a distribution of drug samples may only be made— (i) in response to a written request for drug samples made on a form which meets the re- quirements of subparagraph (B), and (ii) under a system which requires the recipi- ent of the drug sample to execute a written re- ceipt for the drug sample upon its delivery and the return of the receipt to the manufacturer or authorized distributor of record. (B) A written request for a drug sample re- quired by subparagraph (A)(i) shall contain— (i) the name, address, professional designa- tion, and signature of the practitioner making the request, (ii) the identity of the drug sample requested and the quantity requested, (iii) the name of the manufacturer of the drug sample requested, and (iv) the date of the request. (C) Each drug manufacturer or authorized dis- tributor of record which makes distributions by mail or common carrier under this paragraph shall maintain, for a period of 3 years, the re- quest forms submitted for such distributions and the receipts submitted for such distributions and shall maintain a record of distributions of drug samples which identifies the drugs distrib- uted and the recipients of the distributions. Forms, receipts, and records required to be maintained under this subparagraph shall be made available by the drug manufacturer or au- thorized distributor of record to Federal and State officials engaged in the regulation of drugs and in the enforcement of laws applicable to drugs. (3) The manufacturer or authorized distributor of record of a drug subject to subsection (b) may, by means other than mail or common car- rier, distribute drug samples only if the manu- facturer or authorized distributor of record makes the distributions in accordance with sub- paragraph (A) and carries out the activities de- scribed in subparagraphs (B) through (F) as fol- lows: (A) Drug samples may only be distributed— (i) to practitioners licensed to prescribe such drugs if they make a written request for the drug samples, or (ii) at the written request of such a li- censed practitioner, to pharmacies of hos- pitals or other health care entities. A written request for drug samples shall be made on a form which contains the practi- tioner’s name, address, and professional des- ignation, the identity of the drug sample re- quested, the quantity of drug samples re- quested, the name of the manufacturer or au- thorized distributor of record of the drug sam- ple, the date of the request and signature of the practitioner making the request. (B) Drug manufacturers or authorized dis- tributors of record shall store drug samples under conditions that will maintain their sta- bility, integrity, and effectiveness and will as- sure that the drug samples will be free of con- tamination, deterioration, and adulteration. (C) Drug manufacturers or authorized dis- tributors of record shall conduct, at least an- nually, a complete and accurate inventory of all drug samples in the possession of rep- resentatives of the manufacturer or author- ized distributor of record. Drug manufacturers or authorized distributors of record shall maintain lists of the names and address of each of their representatives who distribute drug samples and of the sites where drug sam- Page 169 TITLE 21—FOOD AND DRUGS § 353 ples are stored. Drug manufacturers or author- ized distributors of record shall maintain records for at least 3 years of all drug samples distributed, destroyed, or returned to the man- ufacturer or authorized distributor of record, of all inventories maintained under this sub- paragraph, of all thefts or significant losses of drug samples, and of all requests made under subparagraph (A) for drug samples. Records and lists maintained under this subparagraph shall be made available by the drug manufac- turer or authorized distributor of record to the Secretary upon request. (D) Drug manufacturers or authorized dis- tributors of record shall notify the Secretary of any significant loss of drug samples and any known theft of drug samples. (E) Drug manufacturers or authorized dis- tributors of record shall report to the Sec- retary any conviction of their representatives for violations of subsection (c)(1) or a State law because of the sale, purchase, or trade of a drug sample or the offer to sell, purchase, or trade a drug sample. (F) Drug manufacturers or authorized dis- tributors of record shall provide to the Sec- retary the name and telephone number of the individual responsible for responding to a re- quest for information respecting drug samples. (4) In this subsection, the term ‘‘authorized distributors of record’’ means those distributors with whom a manufacturer has established an ongoing relationship to distribute such manu- facturer’s products. (e) Licensing and reporting requirements for wholesale distributors; fees; definitions (1) REQUIREMENT.—Subject to section 360eee–2 of this title: (A) IN GENERAL.—No person may engage in wholesale distribution of a drug subject to subsection (b)(1) in any State unless such per- son— (i)(I) is licensed by the State from which the drug is distributed; or (II) if the State from which the drug is dis- tributed has not established a licensure re- quirement, is licensed by the Secretary; and (ii) if the drug is distributed interstate, is licensed by the State into which the drug is distributed if the State into which the drug is distributed requires the licensure of a per- son that distributes drugs into the State. (B) STANDARDS.—Each Federal and State li- cense described in subparagraph (A) shall meet the standards, terms, and conditions estab- lished by the Secretary under section 360eee–2 of this title. (2) REPORTING AND DATABASE.— (A) REPORTING.—Beginning January 1, 2015, any person who owns or operates an establish- ment that engages in wholesale distribution shall— (i) report to the Secretary, on an annual basis pursuant to a schedule determined by the Secretary— (I) each State by which the person is li- censed and the appropriate identification number of each such license; and (II) the name, address, and contact infor- mation of each facility at which, and all trade names under which, the person con- ducts business; and (ii) report to the Secretary within a rea- sonable period of time and in a reasonable manner, as determined by the Secretary, any significant disciplinary actions, such as the revocation or suspension of a wholesale distributor license, taken by a State or the Federal Government during the reporting period against the wholesale distributor. (B) DATABASE.—Not later than January 1, 2015, the Secretary shall establish a database of authorized wholesale distributors. Such database shall— (i) identify each authorized wholesale dis- tributor by name, contact information, and each State where such wholesale distributor is appropriately licensed to engage in whole- sale distribution; (ii) be available to the public on the Inter- net Web site of the Food and Drug Adminis- tration; and (iii) be regularly updated on a schedule de- termined by the Secretary. (C) COORDINATION.—The Secretary shall es- tablish a format and procedure for appropriate State officials to access the information pro- vided pursuant to subparagraph (A) in a prompt and secure manner. (D) CONFIDENTIALITY.—Nothing in this para- graph shall be construed as authorizing the Secretary to disclose any information that is a trade secret or confidential information sub- ject to section 552(b)(4) of title 5 or section 1905 of title 18. (3) COSTS.— (A) AUTHORIZED FEES OF SECRETARY.—If a State does not establish a licensing program for persons engaged in the wholesale distribu- tion of a drug subject to subsection (b), the Secretary shall license a person engaged in wholesale distribution located in such State and may collect a reasonable fee in such amount necessary to reimburse the Secretary for costs associated with establishing and ad- ministering the licensure program and con- ducting periodic inspections under this sec- tion. The Secretary shall adjust fee rates as needed on an annual basis to generate only the amount of revenue needed to perform this service. Fees authorized under this paragraph shall be collected and available for obligation only to the extent and in the amount provided in advance in appropriations Acts. Such fees are authorized to remain available until ex- pended. Such sums as may be necessary may be transferred from the Food and Drug Admin- istration salaries and expenses appropriation account without fiscal year limitation to such appropriation account for salaries and ex- penses with such fiscal year limitation. (B) STATE LICENSING FEES.—Nothing in this chapter shall prohibit States from collecting fees from wholesale distributors in connection with State licensing of such distributors. (4) For the purposes of this subsection and sub- section (d), the term ‘‘wholesale distribution’’ means the distribution of a drug subject to sub- section (b) to a person other than a consumer or Page 170 TITLE 21—FOOD AND DRUGS § 353 patient, or receipt of a drug subject to sub- section (b) by a person other than the consumer or patient, but does not include— (A) intracompany distribution of any drug between members of an affiliate or within a manufacturer; (B) the distribution of a drug, or an offer to distribute a drug among hospitals or other health care entities which are under common control; (C) the distribution of a drug or an offer to distribute a drug for emergency medical rea- sons, including a public health emergency dec- laration pursuant to section 319 of the Public Health Service Act [42 U.S.C. 247d], except that, for purposes of this paragraph, a drug shortage not caused by a public health emer- gency shall not constitute an emergency med- ical reason; (D) the dispensing of a drug pursuant to a prescription executed in accordance with sub- section (b)(1); (E) the distribution of minimal quantities of drug by a licensed retail pharmacy to a li- censed practitioner for office use; (F) the distribution of a drug or an offer to distribute a drug by a charitable organization to a nonprofit affiliate of the organization to the extent otherwise permitted by law; (G) the purchase or other acquisition by a dispenser, hospital, or other health care entity of a drug for use by such dispenser, hospital, or other health care entity; (H) the distribution of a drug by the manu- facturer of such drug; (I) the receipt or transfer of a drug by an au- thorized third-party logistics provider pro- vided that such third-party logistics provider does not take ownership of the drug; (J) a common carrier that transports a drug, provided that the common carrier does not take ownership of the drug; (K) the distribution of a drug, or an offer to distribute a drug by an authorized repackager that has taken ownership or possession of the drug and repacks it in accordance with section 360eee–1(e) of this title; (L) salable drug returns when conducted by a dispenser; (M) the distribution of a collection of fin- ished medical devices, which may include a product or biological product, assembled in kit form strictly for the convenience of the pur- chaser or user (referred to in this subpara- graph as a ‘‘medical convenience kit’’) if— (i) the medical convenience kit is assem- bled in an establishment that is registered with the Food and Drug Administration as a device manufacturer in accordance with sec- tion 360(b)(2) of this title; (ii) the medical convenience kit does not contain a controlled substance that appears in a schedule contained in the Comprehen- sive Drug Abuse Prevention and Control Act of 1970 [21 U.S.C. 801 et seq.]; (iii) in the case of a medical convenience kit that includes a product, the person that manufacturers the kit— (I) purchased such product directly from the pharmaceutical manufacturer or from a wholesale distributor that purchased the product directly from the pharmaceutical manufacturer; and (II) does not alter the primary container or label of the product as purchased from the manufacturer or wholesale distributor; and (iv) in the case of a medical convenience kit that includes a product, the product is— (I) an intravenous solution intended for the replenishment of fluids and electro- lytes; (II) a product intended to maintain the equilibrium of water and minerals in the body; (III) a product intended for irrigation or reconstitution; (IV) an anesthetic; (V) an anticoagulant; (VI) a vasopressor; or (VII) a sympathomimetic; (N) the distribution of an intravenous drug that, by its formulation, is intended for the re- plenishment of fluids and electrolytes (such as sodium, chloride, and potassium) or calories (such as dextrose and amino acids); (O) the distribution of an intravenous drug used to maintain the equilibrium of water and minerals in the body, such as dialysis solu- tions; (P) the distribution of a drug that is in- tended for irrigation, or sterile water, whether intended for such purposes or for injection; (Q) the distribution of medical gas, as de- fined in section 360ddd of this title; (R) facilitating the distribution of a product by providing solely administrative services, including processing of orders and payments; or (S) the transfer of a product by a hospital or other health care entity, or by a wholesale dis- tributor or manufacturer operating at the di- rection of the hospital or other health care en- tity, to a repackager described in section 360eee(16)(B) of this title and registered under section 360 of this title for the purpose of re- packaging the drug for use by that hospital, or other health care entity and other health care entities that are under common control, if ownership of the drug remains with the hos- pital or other health care entity at all times. (5) THIRD-PARTY LOGISTICS PROVIDERS.—Not- withstanding paragraphs (1) through (4), each entity that meets the definition of a third-party logistics provider under section 360eee(22) of this title shall obtain a license as a third-party logis- tics provider as described in section 360eee–3(a) of this title and is not required to obtain a li- cense as a wholesale distributor if the entity never assumes an ownership interest in the product it handles. (6) AFFILIATE.—For purposes of this sub- section, the term ‘‘affiliate’’ means a business entity that has a relationship with a second business entity if, directly or indirectly— (A) one business entity controls, or has the power to control, the other business entity; or (B) a third party controls, or has the power to control, both of the business entities. (f) Veterinary prescription drugs (1)(A) A drug intended for use by animals other than man, other than a veterinary feed di- Page 171 TITLE 21—FOOD AND DRUGS § 353 rective drug intended for use in animal feed or an animal feed bearing or containing a veteri- nary feed directive drug, which— (i) because of its toxicity or other poten- tiality for harmful effect, or the method of its use, or the collateral measures necessary for its use, is not safe for animal use except under the professional supervision of a licensed vet- erinarian, or (ii) is limited by an approved application under subsection (b) of section 360b of this title, a conditionally-approved application under section 360ccc of this title, or an index listing under section 360ccc–1 of this title to use under the professional supervision of a li- censed veterinarian, shall be dispensed only by or upon the lawful written or oral order of a licensed veterinarian in the course of the veterinarian’s professional practice. (B) For purposes of subparagraph (A), an order is lawful if the order— (i) is a prescription or other order authorized by law, (ii) is, if an oral order, promptly reduced to writing by the person lawfully filling the order, and filed by that person, and (iii) is refilled only if authorized in the origi- nal order or in a subsequent oral order promptly reduced to writing by the person lawfully filling the order, and filed by that person. (C) 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 mis- branded while held for sale. (2) Any drug when dispensed in accordance with paragraph (1) of this subsection— (A) shall be exempt from the requirements of section 352 of this title, except subsections (a), (g), (h), (i)(2), (i)(3), and (p) of such section, and (B) shall be exempt from the packaging re- quirements of subsections (g), (h), and (p) of such section, if— (i) when dispensed by a licensed veteri- narian, the drug bears a label containing the name and address of the practitioner and any directions for use and cautionary state- ments specified by the practitioner, or (ii) when dispensed by filling the lawful order of a licensed veterinarian, the drug bears a label containing the name and ad- dress of the dispenser, the serial number and date of the order or of its filling, the name of the licensed veterinarian, and the direc- tions for use and cautionary statements, if any, contained in such order. The preceding sentence shall not apply to any drug dispensed in the course of the conduct of a business of dispensing drugs pursuant to diag- nosis by mail. (3) The Secretary may by regulation exempt drugs for animals other than man subject to sec- tion 360b, 360ccc, or 360ccc–1 of this title from the requirements of paragraph (1) when such re- quirements are not necessary for the protection of the public health. (4) A drug which is subject to paragraph (1) shall be deemed to be misbranded if at any time prior to dispensing its label fails to bear the statement ‘‘Caution: Federal law restricts this drug to use by or on the order of a licensed vet- erinarian.’’. A drug to which paragraph (1) does not apply shall be deemed to be misbranded if at any time prior to dispensing its label bears the statement specified in the preceding sentence. (g) Regulation of combination products (1)(A) The Secretary shall, in accordance with this subsection, assign a primary agency center to regulate products that constitute a combina- tion of a drug, device, or biological product. (B) The Secretary shall conduct the premarket review of any combination product under a sin- gle application, whenever appropriate. (C) For purposes of this subsection, the term ‘‘primary mode of action’’ means the single mode of action of a combination product ex- pected to make the greatest contribution to the overall intended therapeutic effects of the com- bination product. (D) The Secretary shall determine the primary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of— (i) a drug (other than a biological product), the agency center charged with premarket re- view of drugs shall have primary jurisdiction; (ii) a device, the agency center charged with premarket review of devices shall have pri- mary jurisdiction; or (iii) a biological product, the agency center charged with premarket review of biological products shall have primary jurisdiction. (E) In determining the primary mode of action of a combination product, the Secretary shall not determine that the primary mode of action is that of a drug or biological product solely be- cause the combination product has any chemical action within or on the human body. (F) If a sponsor of a combination product dis- agrees with the determination under subpara- graph (D)— (i) such sponsor may request, and the Sec- retary shall provide, a substantive rationale to such sponsor that references scientific evi- dence provided by the sponsor and any other scientific evidence relied upon by the Sec- retary to support such determination; and (ii)(I) the sponsor of the combination prod- uct may propose one or more studies (which may be nonclinical, clinical, or both) to estab- lish the relevance, if any, of the chemical ac- tion in achieving the primary mode of action of such product; (II) if the sponsor proposes any such studies, the Secretary and the sponsor of such product shall collaborate and seek to reach agreement, within a reasonable time of such proposal, not to exceed 90 calendar days, on the design of such studies; and (III) if an agreement is reached under sub- clause (II) and the sponsor conducts one or more of such studies, the Secretary shall con- sider the data resulting from any such study when reevaluating the determination of the primary mode of action of such product, and unless and until such reevaluation has oc- curred and the Secretary issues a new deter- mination, the determination of the Secretary under subparagraph (D) shall remain in effect. Page 172 TITLE 21—FOOD AND DRUGS § 353 1 So in original. No subpar. (B) has been enacted. (2)(A) 1 (i) To establish clarity and certainty for the sponsor, the sponsor of a combination product may request a meeting on such com- bination product. If the Secretary concludes that a determination of the primary mode of ac- tion pursuant to paragraph (1)(D) is necessary, the sponsor may request such meeting only after the Secretary makes such determination. If the sponsor submits a written meeting request, the Secretary shall, not later than 75 calendar days after receiving such request, meet with the sponsor of such combination product. (ii) A meeting under clause (i) may— (I) address the standards and requirements for market approval or clearance of the com- bination product; (II) address other issues relevant to such combination product, such as requirements re- lated to postmarket modification of such com- bination product and good manufacturing practices applicable to such combination prod- uct; and (III) identify elements under subclauses (I) and (II) that may be more appropriate for dis- cussion and agreement with the Secretary at a later date given that scientific or other infor- mation is not available, or agreement is other- wise not feasible regarding such elements, at the time a request for such meeting is made. (iii) Any agreement under this subparagraph shall be in writing and made part of the admin- istrative record by the Secretary. (iv) Any such agreement shall remain in ef- fect, except— (I) upon the written agreement of the Sec- retary and the sponsor or applicant; or (II) pursuant to a decision by the director of the reviewing division of the primary agency center, or a person more senior than such di- rector, in consultation with consulting centers and the Office, as appropriate, that an issue essential to determining whether the standard for market clearance or other applicable standard under this chapter or the Public Health Service Act [42 U.S.C. 201 et seq.] appli- cable to the combination product has been identified since the agreement was reached, or that deviating from the agreement is other- wise justifiable based on scientific evidence, for public health reasons. (3) For purposes of conducting the premarket review of a combination product that contains an approved constituent part described in para- graph (4), the Secretary may require that the sponsor of such combination product submit to the Secretary only data or information that the Secretary determines is necessary to meet the standard for clearance or approval, as applica- ble, under this chapter or the Public Health Service Act, including any incremental risks and benefits posed by such combination product, using a risk-based approach and taking into ac- count any prior finding of safety and effective- ness or substantial equivalence for the approved constituent part relied upon by the applicant in accordance with paragraph (5). (4) For purposes of paragraph (3), an approved constituent part is— (A) a drug constituent part of a combination product being reviewed in a single application or request under section 360e, 360(k), or 360c(f)(2) of this title (submitted in accordance with paragraph (5)), that is an approved drug, provided such application or request complies with paragraph (5); (B) a device constituent part approved under section 360e of this title that is referenced by the sponsor and that is available for use by the Secretary under section 360j(h)(4) of this title; or (C) any constituent part that was previously approved, cleared, or classified under section 355, 360(k), 360c(f)(2), or 360e of this title for which the sponsor has a right of reference or any constituent part that is a nonprescription drug, as defined in section 379aa(a)(2) of this title. (5)(A) If an application is submitted under sec- tion 360e or 360(k) of this title or a request is submitted under section 360c(f)(2) of this title, consistent with any determination made under paragraph (1)(D), for a combination product con- taining as a constituent part an approved drug— (i) the application or request shall include the certification or statement described in section 355(b)(2) of this title; and (ii) the applicant or requester shall provide notice as described in section 355(b)(3) of this title. (B) For purposes of this paragraph and para- graph (4), the term ‘‘approved drug’’ means an active ingredient— (i) that was in an application previously ap- proved under section 355(c) of this title; (ii) where such application is relied upon by the applicant submitting the application or re- quest described in subparagraph (A); (iii) for which full reports of investigations that have been made to show whether such drug is safe for use and whether such drug is effective in use were not conducted by or for the applicant submitting the application or re- quest described in subparagraph (A); and (iv) for which the applicant submitting the application or request described in subpara- graph (A) has not obtained a right of reference or use from the person by or for whom the in- vestigations described in clause (iii) were con- ducted. (C) The following provisions shall apply with respect to an application or request described in subparagraph (A) to the same extent and in the same manner as if such application or request were an application described in section 355(b)(2) of this title that referenced the approved drug: (i) Subparagraphs (A), (B), (C), and (D) of section 355(c)(3) of this title. (ii) Clauses (ii), (iii), and (iv) of section 355(c)(3)(E) of this title. (iii) Subsections (b) and (c) of section 355a of this title. (iv) Section 355f(a) of this title. (v) Section 360cc(a) of this title. (D) Notwithstanding any other provision of this subsection, an application or request for classification for a combination product de- scribed in subparagraph (A) shall be considered Page 173 TITLE 21—FOOD AND DRUGS § 353 2 So in original. The word ‘‘and’’ probably should appear. 3 So in original. The semicolon probably should be a period. an application submitted under section 355(b)(2) of this title for purposes of section 271(e)(2)(A) of title 35. (6) Nothing in this subsection shall be con- strued as prohibiting a sponsor from submitting separate applications for the constituent parts of a combination product, unless the Secretary determines that a single application is nec- essary. (7) Nothing in this subsection shall prevent the Secretary from using any agency resources of the Food and Drug Administration necessary to ensure adequate review of the safety, effec- tiveness, or substantial equivalence of an arti- cle. (8)(A) Not later than 60 days after October 26, 2002, the Secretary shall establish within the Of- fice of the Commissioner of Food and Drugs an office to ensure the prompt assignment of com- bination products to agency centers, the timely and effective premarket review of such products, and consistent and appropriate postmarket reg- ulation of like products subject to the same statutory requirements to the extent permitted by law. Additionally, the office shall, in deter- mining whether a product is to be designated a combination product, consult with the compo- nent within the Office of the Commissioner of Food and Drugs that is responsible for such de- terminations. Such office (referred to in this paragraph as the ‘‘Office’’) shall have appro- priate scientific and medical expertise, and shall be headed by a director. (B) In carrying out this subsection, the Office shall, for each combination product, promptly assign an agency center with primary jurisdic- tion in accordance with paragraph (1) for the premarket review of such product. (C)(i) In carrying out this subsection, the Of- fice shall help to ensure timely and effective premarket review that involves more than one agency center by coordinating such reviews, overseeing the timeliness of such reviews, and overseeing the alignment of feedback regarding such reviews. (ii) In order to ensure the timeliness and alignment of the premarket review of a com- bination product, the agency center with pri- mary jurisdiction for the product, and the con- sulting agency center, shall be responsible to the Office with respect to the timeliness and alignment of the premarket review. (iii) The Office shall ensure that, with respect to a combination product, a designated person or persons in the primary agency center is the primary point or points of contact for the spon- sor of such combination product. The Office shall also coordinate communications to and from any consulting center involved in such pre- market review, if requested by such primary agency center or any such consulting center. Agency communications and commitments, to the extent consistent with other provisions of law and the requirements of all affected agency centers, from the primary agency center shall be considered as communication from the Sec- retary on behalf of all agency centers involved in the review. (iv) The Office shall, with respect to the pre- market review of a combination product— (I) ensure that any meeting between the Sec- retary and the sponsor of such product is at- tended by each agency center involved in the review, as appropriate; (II) ensure that each consulting agency cen- ter has completed its premarket review and provided the results of such review to the pri- mary agency center in a timely manner; and (III) ensure that each consulting center fol- lows the guidance described in clause (vi) and advises, as appropriate, on other relevant reg- ulations, guidances, and policies. (v) In seeking agency action with respect to a combination product, the sponsor of such prod- uct— (I) shall identify the product as a combina- tion product; and (II) may request in writing the participation of representatives of the Office in meetings re- lated to such combination product, or to have the Office otherwise engage on such regu- latory matters concerning the combination product. (vi) Not later than 4 years after December 13, 2016, and after a public comment period of not less than 60 calendar days, the Secretary shall issue a final guidance that describes— (I) the structured process for managing pre- submission interactions with sponsors devel- oping combination products; (II) the best practices for ensuring that the feedback in such pre-submission interactions represents the Agency’s best advice based on the information provided during such pre-sub- mission interactions; 2 (III) the information that is required to be submitted with a meeting request under para- graph (2), how such meetings relate to other types of meetings in the Food and Drug Ad- ministration, and the form and content of any agreement reached through a meeting under such paragraph (2); 3 (D) In carrying out this subsection, the Office shall ensure the consistency and appropriate- ness of postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law. (E)(i) Any dispute regarding the timeliness of the premarket review of a combination product may be presented to the Office for resolution, unless the dispute is clearly premature. (ii) During the review process, any dispute re- garding the substance of the premarket review may be presented to the Commissioner of Food and Drugs after first being considered by the agency center with primary jurisdiction of the premarket review, under the scientific dispute resolution procedures for such center. The Com- missioner of Food and Drugs shall consult with the Director of the Office in resolving the sub- stantive dispute. (F) The Secretary, acting through the Office, shall review each agreement, guidance, or prac- tice of the Secretary that is specific to the as- signment of combination products to agency centers and shall determine whether the agree- ment, guidance, or practice is consistent with the requirements of this subsection. In carrying out such review, the Secretary shall consult Page 174 TITLE 21—FOOD AND DRUGS § 353 4 See References in Text note below. 5 So in original. Probably should be followed by a period. with stakeholders and the directors of the agen- cy centers. After such consultation, the Sec- retary shall determine whether to continue in effect, modify, revise, or eliminate such agree- ment, guidance, or practice, and shall publish in the Federal Register a notice of the availability of such modified or revised agreement, guidance or practice. Nothing in this paragraph shall be construed as preventing the Secretary from fol- lowing each agreement, guidance, or practice until continued, modified, revised, or elimi- nated. (G) Not later than one year after October 26, 2002 (except with respect to clause (iv), begin- ning not later than one year after December 13, 2016), and annually thereafter, the Secretary shall report to the appropriate committees of Congress on the activities and impact of the Of- fice. The report shall include provisions— (i) describing the numbers and types of com- bination products under review and the timeli- ness in days of such assignments, reviews, and dispute resolutions; (ii) identifying the number of premarket re- views of such products that involved a con- sulting agency center; (iii) describing improvements in the consist- ency of postmarket regulation of combination products; and (iv) identifying the percentage of combina- tion products for which a dispute resolution, with respect to premarket review, was re- quested by the combination product’s sponsor. (H) Nothing in this paragraph shall be con- strued to limit the regulatory authority of any agency center. (9) As used in this subsection: (A) The term ‘‘agency center’’ means a cen- ter or alternative organizational component of the Food and Drug Administration. (B) The term ‘‘biological product’’ has the meaning given the term in section 351(i) of the Public Health Service Act (42 U.S.C. 262(i)). (C) The term ‘‘market clearance’’ includes— (i) approval of an application under section 355, 357,4 360e, or 360j(g) of this title; (ii) a finding of substantial equivalence under this part; (iii) approval of a biologics license applica- tion under subsection (a) of section 351 of the Public Health Service Act (42 U.S.C. 262); and (iv) de novo classification under section 360c(a)(1) of this title. (D) The terms ‘‘premarket review’’ and ‘‘re- views’’ include all activities of the Food and Drug Administration conducted prior to ap- proval or clearance of an application, notifica- tion, or request for classification submitted under section 355, 360(k), 360c(f)(2), 360e, or 360j of this title or under section 351 of the Public Health Service Act [42 U.S.C. 262], including with respect to investigational use of the product. (h) Regulation of certain products as drugs (1) Any contrast agent, radioactive drug, or OTC monograph drug shall be deemed to be a drug under section 321(g) of this title and not a device under section 321(h) of this title. (2) For purposes of this subsection: (A) The term ‘‘contrast agent’’ means an ar- ticle that is intended for use in conjunction with a medical imaging device, and— (i) is a diagnostic radiopharmaceutical, as defined in sections 315.2 and 601.31 of title 21, Code of Federal Regulations (or any suc- cessor regulations); or (ii) is a diagnostic agent that improves the visualization of structure or function within the body by increasing the relative dif- ference in signal intensity within the target tissue, structure, or fluid. (B) The term ‘‘radioactive drug’’ has the meaning given such term in section 310.3(n) of title 21, Code of Federal Regulations (or any successor regulations), except that such term does not include— (i) an implant or article similar to an im- plant; (ii) an article that applies radiation from outside of the body; or (iii) the radiation source of an article de- scribed in clause (i) or (ii). (C) The term ‘‘OTC monograph drug’’ has the meaning given such term in section 379j–71 of this title. (3) Nothing in this subsection shall be con- strued as allowing for the classification of a product as a drug (as defined in section 321(g) of this title) if such product— (A) is not described in paragraph (1); and (B) meets the definition of a device under section 321(h) of this title, unless another provision of this chapter other- wise indicates a different classification. (4) The Secretary shall waive the application fee under sections 379h and 379j–42 of this title for applications for drugs that are— (A) on September 30, 2022, legally marketed as devices; and (B) deemed drugs pursuant to paragraph (1) 5 (June 25, 1938, ch. 675, § 503, 52 Stat. 1051; Oct. 26, 1951, ch. 578, § 1, 65 Stat. 648; Pub. L. 87–781, title I, § 104(e)(2), Oct. 10, 1962, 76 Stat. 785; Pub. L. 91–601, § 6(e), formerly § 7(e), Dec. 30, 1970, 84 Stat. 1673, renumbered Pub. L. 97–35, title XII, § 1205(c), Aug. 13, 1981, 95 Stat. 716; Pub. L. 100–293, §§ 4–6, Apr. 22, 1988, 102 Stat. 96–98; Pub. L. 100–670, title I, § 105, Nov. 16, 1988, 102 Stat. 3983; Pub. L. 101–629, § 16(a), Nov. 28, 1990, 104 Stat. 4526; Pub. L. 102–108, § 2(d), Aug. 17, 1991, 105 Stat. 550; Pub. L. 102–300, § 6(d), June 16, 1992, 106 Stat. 240; Pub. L. 102–353, §§ 2(a)–(c), 4, Aug. 26, 1992, 106 Stat. 941, 942; Pub. L. 104–250, § 5(a), Oct. 9, 1996, 110 Stat. 3155; Pub. L. 105–115, title I, §§ 123(e), 126(a), (c)(1), (2), Nov. 21, 1997, 111 Stat. 2324, 2327, 2328; Pub. L. 107–250, title II, § 204, Oct. 26, 2002, 116 Stat. 1611; Pub. L. 108–282, title I, § 102(b)(5)(F), Aug. 2, 2004, 118 Stat. 903; Pub. L. 113–54, title II, § 204(a)(1)–(4), (b), Nov. 27, 2013, 127 Stat. 630–635; Pub. L. 114–255, div. A, title III, § 3038(a), Dec. 13, 2016, 130 Stat. 1105; Pub. L. 117–328, div. FF, title III, § 3621, Dec. 29, 2022, 136 Stat. 5877.) Page 175 TITLE 21—FOOD AND DRUGS § 353 Editorial Notes REFERENCES IN TEXT The Comprehensive Drug Abuse Prevention and Con- trol Act of 1970, referred to in subsec. (e)(4)(M)(ii), is Pub. L. 91–513, Oct. 27, 1970, 84 Stat. 1236, which is clas- sified principally to chapter 13 (§ 801 et seq.) of this title. For complete classification of this Act to the Code, see Short Title note set out under section 801 of this title and Tables. The Public Health Service Act, referred to in subsec. (g)(2)(A)(iv)(II), (3), is act July 1, 1944, ch. 373, 58 Stat. 682, which is classified generally to chapter 6A (§ 201 et seq.) of Title 42, The Public Health and Welfare. For complete classification of this Act to the Code, see Short Title note set out under section 201 of Title 42 and Tables. Section 357 of this title, referred to in subsec. (g)(9)(C)(i), was repealed by Pub. L. 105–115, title I, § 125(b)(1), Nov. 21, 1997, 111 Stat. 2325. CODIFICATION In subsec. (b)(5), ‘‘sections 4721, 6001, and 6151 of title 26’’ and ‘‘section 4761 of title 26’’ substituted for ‘‘sec- tion 3220 of the Internal Revenue Code (26 U.S.C. 3220)’’ and ‘‘section 3238(b) of the Internal Revenue Code (26 U.S.C. 3238(b))’’, respectively, on authority of section 7852(b) of Title 26, Internal Revenue Code. AMENDMENTS 2022—Subsec. (h). Pub. L. 117–328 added subsec. (h). 2016—Subsec. (g)(1). Pub. L. 114–255, § 3038(a)(4), added par. (1) and struck out former par. (1) which read as fol- lows: ‘‘The Secretary shall in accordance with this sub- section assign an agency center to regulate products that constitute a combination of a drug, device, or bio- logical product. The Secretary shall determine the pri- mary mode of action of the combination product. If the Secretary determines that the primary mode of action is that of— ‘‘(A) a drug (other than a biological product), the agency center charged with premarket review of drugs shall have primary jurisdiction, ‘‘(B) a device, the agency center charged with pre- market review of devices shall have primary jurisdic- tion, or ‘‘(C) a biological product, the agency center charged with premarket review of biological products shall have primary jurisdiction.’’ Subsec. (g)(2). Pub. L. 114–255, § 3038(a)(4), added par. (2). Former par. (2) redesignated (7). Subsec. (g)(3). Pub. L. 114–255, § 3038(a)(1), (4), added par. (3) and struck out former par. (3) which read as fol- lows: ‘‘The Secretary shall promulgate regulations to implement market clearance procedures in accordance with paragraphs (1) and (2) not later than 1 year after November 28, 1990.’’ Subsec. (g)(4) to (6). Pub. L. 114–255, § 3038(a)(4), added pars. (4) to (6). Former pars. (4) and (5) redesignated (8) and (9), respectively. Subsec. (g)(7). Pub. L. 114–255, § 3038(a)(2), redesig- nated par. (2) as (7). Subsec. (g)(8). Pub. L. 114–255, § 3038(a)(3), redesig- nated par. (4) as (8). Subsec. (g)(8)(C)(i). Pub. L. 114–255, § 3038(a)(5)(A)(i), amended cl. (i) generally. Prior to amendment, cl. (i) read as follows: ‘‘In carrying out this subsection, the Office shall ensure timely and effective premarket re- views by overseeing the timeliness of and coordinating reviews involving more than one agency center.’’ Subsec. (g)(8)(C)(ii). Pub. L. 114–255, § 3038(a)(5)(A)(ii), inserted ‘‘and alignment’’ after ‘‘the timeliness’’ in two places. Subsec. (g)(8)(C)(iii) to (vi). Pub. L. 114–255, § 3038(a)(5)(A)(iii), added cls. (iii) to (vi). Subsec. (g)(8)(G). Pub. L. 114–255, § 3038(a)(5)(B)(i), in- serted ‘‘(except with respect to clause (iv), beginning not later than one year after December 13, 2016)’’ after ‘‘October 26, 2002’’ in introductory provisions. Subsec. (g)(8)(G)(iv). Pub. L. 114–255, § 3038(a)(5)(B)(ii)–(iv), added cl. (iv). Subsec. (g)(9). Pub. L. 114–255, § 3038(a)(3), redesig- nated par. (5) as (9). Subsec. (g)(9)(C). Pub. L. 114–255, § 3038(a)(6)(A), sub- stituted semicolon for comma at end of cl. (i), semi- colon for ‘‘, and’’ at end of cl. (ii), and ‘‘; and’’ for pe- riod at end of cl. (iii), and added cl. (iv). Subsec. (g)(9)(D). Pub. L. 114–255, § 3038(a)(6)(B), added subpar. (D). 2013—Subsec. (d)(4). Pub. L. 113–54, § 204(b), added par. (4). Subsec. (e). Pub. L. 113–54, § 204(a)(1)–(4), added pars. (1) to (6) and struck out former pars. (1) to (3). Prior to amendment, pars. (1) to (3) set out certain disclosure and licensing requirements for wholesale distributors and defined ‘‘authorized distributors of record’’ and ‘‘wholesale distribution’’. 2004—Subsec. (f)(1)(A)(ii). Pub. L. 108–282, § 102(b)(5)(F)(i), substituted ‘‘360b of this title, a condi- tionally-approved application under section 360ccc of this title, or an index listing under section 360ccc–1 of this title’’ for ‘‘360b of this title’’. Subsec. (f)(3). Pub. L. 108–282, § 102(b)(5)(F)(ii), sub- stituted ‘‘section 360b, 360ccc, or 360ccc–1’’ for ‘‘section 360b’’. 2002—Subsec. (g)(1). Pub. L. 107–250, § 204(1)(A), sub- stituted ‘‘shall in accordance with this subsection as- sign an agency center’’ for ‘‘shall designate a compo- nent of the Food and Drug Administration’’ in first sentence of introductory provisions. Subsec. (g)(1)(A) to (C). Pub. L. 107–250, § 204(1)(B), substituted ‘‘the agency center charged’’ for ‘‘the per- sons charged’’. Subsec. (g)(4). Pub. L. 107–250, § 204(3), added par. (4). Former par. (4) redesignated (5). Subsec. (g)(5). Pub. L. 107–250, § 204(2), (4), redesig- nated par. (4) as (5), added subpar. (A), and redesignated former subpars. (A) and (B) as (B) and (C), respectively. 1997—Subsec. (b)(1)(A) to (C). Pub. L. 105–115, § 126(c)(1), redesignated subpars. (B) and (C) as (A) and (B), respectively, and struck out former subpar. (A), which read as follows: ‘‘is a habit-forming drug to which section 352(d) of this title applies; or’’. Subsec. (b)(3). Pub. L. 105–115, § 126(c)(2), struck out reference to section 352(d) of this title before ‘‘355’’. Subsec. (b)(4). Pub. L. 105–115, § 126(a), amended par. (4) generally. Prior to amendment, par. (4) read as fol- lows: ‘‘A drug which is subject to paragraph (1) of this subsection shall be deemed to be misbranded if at any time prior to dispensing its label fails to bear the state- ment ‘Caution: Federal law prohibits dispensing with- out prescription’. A drug to which paragraph (1) of this subsection does not apply shall be deemed to be mis- branded if at any time prior to dispensing its label bears the caution statement quoted in the preceding sentence.’’ Subsec. (g)(4)(A). Pub. L. 105–115, § 123(e)(1), sub- stituted ‘‘section 351(i)’’ for ‘‘section 351(a)’’ and ‘‘262(i)’’ for ‘‘262(a)’’. Subsec. (g)(4)(B)(iii). Pub. L. 105–115, § 123(e)(2), sub- stituted ‘‘biologics license application under subsection (a)’’ for ‘‘product or establishment license under sub- section (a) or (d)’’. 1996—Subsec. (f)(1)(A). Pub. L. 104–250 inserted ‘‘, other than a veterinary feed directive drug intended for use in animal feed or an animal feed bearing or con- taining a veterinary feed directive drug,’’ after ‘‘other than man’’ in introductory provisions. 1992—Subsec. (d)(1). Pub. L. 102–353, § 4(1), amended par. (1) generally. Prior to amendment, par. (1) read as follows: ‘‘Except as provided in paragraphs (2) and (3), no representative of a drug manufacturer or distributor may distribute any drug sample.’’ Subsec. (d)(2). Pub. L. 102–353, § 4(2), substituted ‘‘au- thorized distributor of record’’ for ‘‘distributor’’ wher- ever appearing. Subsec. (d)(3). Pub. L. 102–353, § 4(2), substituted ‘‘au- thorized distributor of record’’ for ‘‘distributor’’ and ‘‘authorized distributors of record’’ for ‘‘distributors’’ wherever appearing. Page 176 TITLE 21—FOOD AND DRUGS § 353 Subsec. (e)(1). Pub. L. 102–353, § 4(3), amended par. (1) generally. Prior to amendment, par. (1) read as follows: ‘‘Each person who is engaged in the wholesale distribu- tion of drugs subject to subsection (b) of this section and who is not an authorized distributor of record of such drugs shall provide to each wholesale distributor of such drugs a statement identifying each sale of the drug (including the date of the sale) before the sale to such wholesale distributor. Each manufacturer shall maintain at its corporate offices a current list of such authorized distributors.’’ Subsec. (e)(2)(A). Pub. L. 102–353, § 2(a), (d), tempo- rarily inserted ‘‘or has registered with the Secretary in accordance with paragraph (3)’’. See Termination Date of 1992 Amendment note below. Subsec. (e)(3). Pub. L. 102–353, § 2(b), (d), temporarily added par. (3). Former par. (3) redesignated (4). See Ter- mination Date of 1992 Amendment note below. Subsec. (e)(4). Pub. L. 102–353, § 4(4), inserted ‘‘and subsection (d) of this section’’ after ‘‘For the purposes of this subsection’’. Pub. L. 102–353, § 2(b), (d), temporarily redesignated par. (3) as (4). See Termination Date of 1992 Amendment note below. Subsec. (f)(1)(B). Pub. L. 102–353, § 2(c), which directed the substitution of ‘‘an order’’ for ‘‘and order’’, could not be executed because ‘‘and order’’ did not appear in subpar. (B). Subsec. (g)(3). Pub. L. 102–300 substituted ‘‘clearance’’ for ‘‘approval’’. 1991—Subsec. (c). Pub. L. 102–108, § 2(d)(3), redesig- nated subsec. (c), relating to veterinary prescription drugs, as (f). Former subsec. (f) redesignated (g). Subsec. (c)(2), (3)(B)(v). Pub. L. 102–108, § 2(d)(1), made technical amendment to reference to subsection (b) of this section involving corresponding provision of origi- nal act. Subsec. (d)(3)(E). Pub. L. 102–108, § 2(d)(2), made tech- nical amendment to reference to subsection (c)(1) of this section involving corresponding provision of origi- nal act. Subsec. (f). Pub. L. 102–108, § 2(d)(4), redesignated sub- sec. (f), relating to regulation of combination products, as (g). Pub. L. 102–108, § 2(d)(3), redesignated subsec. (c), re- lating to veterinary prescription drugs, as (f). Subsec. (g). Pub. L. 102–108, § 2(d)(4), redesignated sub- sec. (f), relating to regulation of combination products, as (g). 1990—Pub. L. 101–629, § 16(a)(1), substituted ‘‘Exemp- tions and consideration for certain drugs, devices, and biological products’’ for ‘‘Exemptions in case of drugs and devices’’ in section catchline. Subsec. (f). Pub. L. 101–629, § 16(a)(2), added subsec. (f). 1988—Subsec. (c). Pub. L. 100–670 added subsec. (c) re- lating to veterinary prescription drugs. Pub. L. 100–293, § 4, added subsec. (c) relating to sales restrictions. Subsec. (d). Pub. L. 100–293, § 5, added subsec. (d). Subsec. (e). Pub. L. 100–293, § 6, added subsec. (e). 1970—Subsec. (b)(2). Pub. L. 91–601 included exemption from packaging requirements of subsec. (p) of section 352 of this title. 1962—Subsec. (b)(1)(C). Pub. L. 87–781 substituted ‘‘ap- proved’’ for ‘‘effective’’. 1951—Subsec. (b). Act Oct. 26, 1951, amended subsec. (b) generally to protect the public from abuses in the sale of potent prescription drugs, and to relieve retail pharmacists and the public from unnecessary restric- tions on the dispensation of drugs that are safe to use without supervision of a doctor. Statutory Notes and Related Subsidiaries EFFECTIVE DATE OF 2013 AMENDMENT Pub. L. 113–54, title II, § 204(c), Nov. 27, 2013, 127 Stat. 636, provided that: ‘‘The amendments made by sub- sections (a) and (b) [enacting section 360eee–2 of this title and amending this section] shall take effect on January 1, 2015.’’ EFFECTIVE DATE OF 1997 AMENDMENT Amendment by Pub. L. 105–115 effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Pub. L. 105–115, set out as a note under section 321 of this title. TERMINATION DATE OF 1992 AMENDMENT Pub. L. 102–353, § 2(d), Aug. 26, 1992, 106 Stat. 941, pro- vided that: ‘‘Effective September 14, 1994, the amend- ments made by subsections (a) and (b) [amending this section] shall no longer be in effect.’’ EFFECTIVE DATE OF 1988 AMENDMENT Pub. L. 100–293, § 8, Apr. 22, 1988, 102 Stat. 100, provided that: ‘‘(a) GENERAL RULE.—Except as provided in sub- section (b), this Act and the amendments made by this Act [amending this section and sections 331, 333, and 381 of this title and enacting provisions set out as notes under this section and section 301 of this title] shall take effect upon the expiration of 90 days after the date of the enactment of this Act [Apr. 22, 1988]. ‘‘(b) EXCEPTION.— ‘‘(1) Section 503(d) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 353(d)] (as added by section 5 of this Act) shall take effect upon the expiration of 180 days after the date of the enactment of this Act [Apr. 22, 1988]. ‘‘(2) The Secretary of Health and Human Services shall by regulation issue the guidelines required by section 503(e)(2)(B) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 353(e)(2)(B)] (as added by sec- tion 6 of this Act) not later than 180 days after the date of the enactment of this Act. Section 503(e)(2)(A) of such Act shall take effect upon the expiration of 2 years after the date such regulations are promulgated and take effect.’’ EFFECTIVE DATE OF 1970 AMENDMENT Amendment by Pub. L. 91–601 effective Dec. 30, 1970, and regulations establishing special packaging stand- ards effective no sooner than 180 days or later than one year from date regulations are final, or an earlier date published in Federal Register, see section 8 of Pub. L. 91–601, set out as an Effective Date note under section 1471 of Title 15, Commerce and Trade. EFFECTIVE DATE OF 1962 AMENDMENT Amendment by Pub. L. 87–781 effective Oct. 10, 1962, see section 107 of Pub. L. 87–781, set out as a note under section 321 of this title. EFFECTIVE DATE OF 1951 AMENDMENT Amendment by act Oct. 26, 1951, effective six months after Oct. 26, 1951, see section 3 of act Oct. 26, 1951, set out as a note under section 333 of this title. EFFECTIVE MEDICATION GUIDES Pub. L. 104–180, title VI, § 601, Aug. 6, 1996, 110 Stat. 1593, provided that: ‘‘(a) IN GENERAL.—Not later than 30 days after the date of enactment of this Act [Aug. 6, 1996], the Sec- retary of the Department of Health and Human Serv- ices shall request that national organizations rep- resenting health care professionals, consumer organiza- tions, voluntary health agencies, the pharmaceutical industry, drug wholesalers, patient drug information database companies, and other relevant parties collabo- rate to develop a long-range comprehensive action plan to achieve goals consistent with the goals of the pro- posed rule of the Food and Drug Administration on ‘Prescription Drug Product Labeling: Medication Guide Requirements’ (60 Fed. Reg. 44182; relating to the provi- sion of oral and written prescription information to consumers). ‘‘(b) GOALS.—Goals consistent with the proposed rule described in subsection (a) are the distribution of use- ful written information to 75 percent of individuals re- Page 177 TITLE 21—FOOD AND DRUGS § 353a ceiving new precriptions [sic] by the year 2000 and to 95 percent by the year 2006. ‘‘(c) PLAN.—The plan described in subsection (a) shall— ‘‘(1) identify the plan goals; ‘‘(2) assess the effectiveness of the current private- sector approaches used to provide oral and written prescription information to consumers; ‘‘(3) develop guidelines for providing effective oral and written prescription information consistent with the findings of any such assessment; ‘‘(4) contain elements necessary to ensure the transmittal of useful information to the consuming public, including being scientifically accurate, non- promotional in tone and content, sufficiently specific and comprehensive as to adequately inform con- sumers about the use of the product, and in an under- standable, legible format that is readily comprehen- sible and not confusing to consumers expected to use the product.[;] ‘‘(5) develop a mechanism to assess periodically the quality of the oral and written prescription informa- tion and the frequency with which the information is provided to consumers; and ‘‘(6) provide for compliance with relevant State board regulations. ‘‘(d) LIMITATION ON THE AUTHORITY OF THE SEC- RETARY.—The Secretary of the Department of Health and Human Services shall have no authority to imple- ment the proposed rule described in subsection (a), or to develop any similar regulation, policy statement, or other guideline specifying a uniform content or format for written information voluntarily provided to con- sumers about prescription drugs if, (1) not later than 120 days after the date of enactment of this Act [Aug. 6, 1996], the national organizations described in sub- section (a) develop and submit to the Secretary for Health and Human Services a comprehensive, long- range action plan (as described in subsection (a)) which shall be acceptable to the Secretary of Health and Human Services; (2) the aforementioned plan is sub- mitted to the Secretary of Health and Human Services for review and acceptance: Provided, That the Secretary shall give due consideration to the submitted plan and that any such acceptance shall not be arbitrarily with- held; and (3) the implementation of (a) a plan accepted by the Secretary commences within 30 days of the Sec- retary’s acceptance of such plan, or (b) the plan sub- mitted to the Secretary commences within 60 days of the submission of such plan if the Secretary fails to take any action on the plan within 30 days of the sub- mission of the plan. The Secretary shall accept, reject or suggest modifications to the plan submitted within 30 days of its submission. The Secretary may confer with and assist private parties in the development of the plan described in subsections (a) and (b). ‘‘(e) SECRETARY REVIEW.—Not later than January 1, 2001, the Secretary of the Department of Health and Human Services shall review the status of private-sec- tor initiatives designed to achieve the goals of the plan described in subsection (a), and if such goals are not achieved, the limitation in subsection (d) shall not apply, and the Secretary shall seek public comment on other initiatives that may be carried out to meet such goals.’’ CONGRESSIONAL FINDINGS Pub. L. 100–293, § 2, Apr. 22, 1988, 102 Stat. 95, provided that: ‘‘The Congress finds the following: ‘‘(1) American consumers cannot purchase prescrip- tion drugs with the certainty that the products are safe and effective. ‘‘(2) The integrity of the distribution system for prescription drugs is insufficient to prevent the intro- duction and eventual retail sale of substandard, inef- fective, or even counterfeit drugs. ‘‘(3) The existence and operation of a wholesale sub- market, commonly known as the ‘diversion market’, prevents effective control over or even routine knowledge of the true sources of prescription drugs in a significant number of cases. ‘‘(4) Large amounts of drugs are being reimported to the United States as American goods returned. These imports are a health and safety risk to Amer- ican consumers because they may have become sub- potent or adulterated during foreign handling and shipping. ‘‘(5) The ready market for prescription drug re- imports has been the catalyst for a continuing series of frauds against American manufacturers and has provided the cover for the importation of foreign counterfeit drugs. ‘‘(6) The existing system of providing drug samples to physicians through manufacturer’s representatives has been abused for decades and has resulted in the sale to consumers of misbranded, expired, and adul- terated pharmaceuticals. ‘‘(7) The bulk resale of below wholesale priced pre- scription drugs by health care entities, for ultimate sale at retail, helps fuel the diversion market and is an unfair form of competition to wholesalers and re- tailers that must pay otherwise prevailing market prices. ‘‘(8) The effect of these several practices and condi- tions is to create an unacceptable risk that counter- feit, adulterated, misbranded, subpotent, or expired drugs will be sold to American consumers.’’ Executive Documents TRANSFER OF FUNCTIONS For transfer of functions of Federal Security Admin- istrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see notes set out under section 321 of this title. § 353a. Pharmacy compounding (a) In general Sections 351(a)(2)(B), 352(f)(1), and 355 of this title shall not apply to a drug product if the drug product is compounded for an identified in- dividual patient based on the receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient, if the drug product meets the requirements of this section, and if the compounding— (1) is by— (A) a licensed pharmacist in a State li- censed pharmacy or a Federal facility, or (B) a licensed physician, on the prescription order for such individual patient made by a licensed physician or other licensed practitioner authorized by State law to prescribe drugs; or (2)(A) is by a licensed pharmacist or licensed physician in limited quantities before the re- ceipt of a valid prescription order for such in- dividual patient; and (B) is based on a history of the licensed pharmacist or licensed physician receiving valid prescription orders for the compounding of the drug product, which orders have been generated solely within an established rela- tionship between— (i) the licensed pharmacist or licensed phy- sician; and (ii)(I) such individual patient for whom the prescription order will be provided; or (II) the physician or other licensed practi- tioner who will write such prescription order.