21 USC 353 - Exemptions and consideration for certain drugs, devices, and biological products

U.S Code last checked for updates: Nov 22, 2024

§ 353.

Exemptions and consideration for certain drugs, devices, and biological products

(a)

Regulations for goods to be processed, labeled, or repacked elsewhere

(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—

(A)

because of its toxicity or other potentiality 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 supervision 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 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.

(2)

Any drug dispensed by filling or refilling a written or oral prescription of a practitioner licensed 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 prescription or of its filling, the name of the prescriber, 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 pursuant 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 construed to relieve any person from any requirement prescribed by or under authority of law with respect to drugs now included or which may hereafter be included within the classifications 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 intended 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 manufacturer or distributor to criminal liability solely because of a sale, purchase, trade, or offer to sell, purchase, or trade in violation of this paragraph 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 redeemed, at no cost or at a reduced cost, for a drug which is prescribed in accordance with subsection (b).

(3)

(A)

No person may sell, purchase, or trade, or offer to sell, purchase, or trade, any drug—

(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 reduced price to a charitable organization described 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 purchasing 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 organization 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 “entity” 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 “distribute” 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 direction 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 direction of such a practitioner and that received such sample pursuant to paragraph (2) or (3).

(2)

(A)

The manufacturer or authorized distributor of record of a drug subject to subsection (b) may, in accordance with this paragraph, distribute 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 entities. 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 requirements of subparagraph (B), and

(ii)

under a system which requires the recipient of the drug sample to execute a written receipt 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 required by subparagraph (A)(i) shall contain—

(i)

the name, address, professional designation, 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 distributor of record which makes distributions by mail or common carrier under this paragraph shall maintain, for a period of 3 years, the request 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 distributed 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 authorized 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 carrier, distribute drug samples only if the manufacturer or authorized distributor of record makes the distributions in accordance with subparagraph (A) and carries out the activities described in subparagraphs (B) through (F) as follows:

(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 licensed practitioner, to pharmacies of hospitals or other health care entities.

A written request for drug samples shall be made on a form which contains the practitioner’s name, address, and professional designation, the identity of the drug sample requested, the quantity of drug samples requested, the name of the manufacturer or authorized distributor of record of the drug sample, the date of the request and signature of the practitioner making the request.

(B)

Drug manufacturers or authorized distributors of record shall store drug samples under conditions that will maintain their stability, integrity, and effectiveness and will assure that the drug samples will be free of contamination, deterioration, and adulteration.

(C)

Drug manufacturers or authorized distributors of record shall conduct, at least annually, a complete and accurate inventory of all drug samples in the possession of representatives of the manufacturer or authorized 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 samples are stored. Drug manufacturers or authorized distributors of record shall maintain records for at least 3 years of all drug samples distributed, destroyed, or returned to the manufacturer or authorized distributor of record, of all inventories maintained under this subparagraph, 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 manufacturer or authorized distributor of record to the Secretary upon request.

(D)

Drug manufacturers or authorized distributors 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 distributors of record shall report to the Secretary 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 distributors of record shall provide to the Secretary the name and telephone number of the individual responsible for responding to a request 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 manufacturer’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 person—

(i)

(I)

is licensed by the State from which the drug is distributed; or

(II)

if the State from which the drug is distributed has not established a licensure requirement, 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 person that distributes drugs into the State.

(B)

Standards.—

Each Federal and State license described in subparagraph (A) shall meet the standards, terms, and conditions established 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 establishment 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 licensed and the appropriate identification number of each such license; and

(II)

the name, address, and contact information of each facility at which, and all trade names under which, the person conducts business; and

(ii)

report to the Secretary within a reasonable 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 distributor by name, contact information, and each State where such wholesale distributor is appropriately licensed to engage in wholesale distribution;

(ii)

be available to the public on the Internet Web site of the Food and Drug Administration; and

(iii)

be regularly updated on a schedule determined by the Secretary.

(C)

Coordination.—

The Secretary shall establish a format and procedure for appropriate State officials to access the information provided pursuant to subparagraph (A) in a prompt and secure manner.

(D)

Confidentiality.—

Nothing in this paragraph shall be construed as authorizing the Secretary to disclose any information that is a trade secret or confidential information subject 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 distribution 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 administering the licensure program and conducting periodic inspections under this section. 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 expended. Such sums as may be necessary may be transferred from the Food and Drug Administration salaries and expenses appropriation account without fiscal year limitation to such appropriation account for salaries and expenses 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 subsection (d), the term “wholesale distribution” means the distribution of a drug subject to subsection (b) to a person other than a consumer or patient, or receipt of a drug subject to subsection (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 reasons, including a public health emergency declaration 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 emergency shall not constitute an emergency medical reason;

(D)

the dispensing of a drug pursuant to a prescription executed in accordance with subsection (b)(1);

(E)

the distribution of minimal quantities of drug by a licensed retail pharmacy to a licensed 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 manufacturer of such drug;

(I)

the receipt or transfer of a drug by an authorized third-party logistics provider provided 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 finished medical devices, which may include a product or biological product, assembled in kit form strictly for the convenience of the purchaser or user (referred to in this subparagraph as a “medical convenience kit”) if—

(i)

the medical convenience kit is assembled in an establishment that is registered with the Food and Drug Administration as a device manufacturer in accordance with section 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 Comprehensive 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 electrolytes;

(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 replenishment 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 solutions;

(P)

the distribution of a drug that is intended for irrigation, or sterile water, whether intended for such purposes or for injection;

(Q)

the distribution of medical gas, as defined 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 distributor or manufacturer operating at the direction of the hospital or other health care entity, to a repackager described in section 360eee(16)(B) of this title and registered under section 360 of this title for the purpose of repackaging 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 hospital or other health care entity at all times.

(5)

Third-party logistics providers.—

Notwithstanding 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 logistics provider as described in section 360eee–3(a) of this title and is not required to obtain a license as a wholesale distributor if the entity never assumes an ownership interest in the product it handles.

(6)

Affiliate.—

For purposes of this subsection, 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 directive drug intended for use in animal feed or an animal feed bearing or containing a veterinary feed directive drug, which—

(i)

because of its toxicity or other potentiality 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 veterinarian, 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 licensed 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 original 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 misbranded 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 requirements of subsections (g), (h), and (p) of such section, if—

(i)

when dispensed by a licensed veterinarian, the drug bears a label containing the name and address of the practitioner and any directions for use and cautionary statements 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 address of the dispenser, the serial number and date of the order or of its filling, the name of the licensed veterinarian, and the directions 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 diagnosis by mail.

(3)

The Secretary may by regulation exempt drugs for animals other than man subject to section 360b, 360ccc, or 360ccc–1 of this title from the requirements of paragraph (1) when such requirements 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 veterinarian.”. 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 combination of a drug, device, or biological product.

(B)

The Secretary shall conduct the premarket review of any combination product under a single 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 expected to make the greatest contribution to the overall intended therapeutic effects of the combination 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 review of drugs shall have primary jurisdiction;

(ii)

a device, the agency center charged with premarket review of devices shall have primary 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 because the combination product has any chemical action within or on the human body.

(F)

If a sponsor of a combination product disagrees with the determination under subparagraph (D)—

(i)

such sponsor may request, and the Secretary shall provide, a substantive rationale to such sponsor that references scientific evidence provided by the sponsor and any other scientific evidence relied upon by the Secretary to support such determination; and

(ii)

(I)

the sponsor of the combination product may propose one or more studies (which may be nonclinical, clinical, or both) to establish the relevance, if any, of the chemical action 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 subclause (II) and the sponsor conducts one or more of such studies, the Secretary shall consider 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 occurred and the Secretary issues a new determination, the determination of the Secretary under subparagraph (D) shall remain in effect.

(2)

(A)

 So in original. No subpar. (B) has been enacted.

 (i) To establish clarity and certainty for the sponsor, the sponsor of a combination product may request a meeting on such combination product. If the Secretary concludes that a determination of the primary mode of action 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 combination product;

(II)

address other issues relevant to such combination product, such as requirements related to postmarket modification of such combination product and good manufacturing practices applicable to such combination product; and

(III)

identify elements under subclauses (I) and (II) that may be more appropriate for discussion and agreement with the Secretary at a later date given that scientific or other information is not available, or agreement is otherwise 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 administrative record by the Secretary.

(iv)

Any such agreement shall remain in effect, except—

(I)

upon the written agreement of the Secretary 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 director, 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.] applicable to the combination product has been identified since the agreement was reached, or that deviating from the agreement is otherwise 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 paragraph (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 applicable, 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 account any prior finding of safety and effectiveness 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 section 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 containing 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 paragraph (4), the term “approved drug” means an active ingredient—

(i)

that was in an application previously approved under section 355(c) of this title;

(ii)

where such application is relied upon by the applicant submitting the application or request 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 request described in subparagraph (A); and

(iv)

for which the applicant submitting the application or request described in subparagraph (A) has not obtained a right of reference or use from the person by or for whom the investigations described in clause (iii) were conducted.

(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 described in subparagraph (A) shall be considered 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 construed 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 necessary.

(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, effectiveness, or substantial equivalence of an article.

(8)

(A)

Not later than 60 days after October 26, 2002, the Secretary shall establish within the Office of the Commissioner of Food and Drugs an office to ensure the prompt assignment of combination products to agency centers, the timely and effective premarket review of such products, and consistent and appropriate postmarket regulation of like products subject to the same statutory requirements to the extent permitted by law. Additionally, the office shall, in determining whether a product is to be designated a combination product, consult with the component within the Office of the Commissioner of Food and Drugs that is responsible for such determinations. Such office (referred to in this paragraph as the “Office”) shall have appropriate 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 jurisdiction in accordance with paragraph (1) for the premarket review of such product.

(C)

(i)

In carrying out this subsection, the Office 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 combination product, the agency center with primary jurisdiction for the product, and the consulting 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 sponsor of such combination product. The Office shall also coordinate communications to and from any consulting center involved in such premarket 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 Secretary on behalf of all agency centers involved in the review.

(iv)

The Office shall, with respect to the premarket review of a combination product—

(I)

ensure that any meeting between the Secretary and the sponsor of such product is attended by each agency center involved in the review, as appropriate;

(II)

ensure that each consulting agency center has completed its premarket review and provided the results of such review to the primary agency center in a timely manner; and

(III)

ensure that each consulting center follows the guidance described in clause (vi) and advises, as appropriate, on other relevant regulations, guidances, and policies.

(v)

In seeking agency action with respect to a combination product, the sponsor of such product—

(I)

shall identify the product as a combination product; and

(II)

may request in writing the participation of representatives of the Office in meetings related to such combination product, or to have the Office otherwise engage on such regulatory 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 developing 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-submission interactions; 2

 So in original. The word “and” probably should appear.

(III)

the information that is required to be submitted with a meeting request under paragraph (2), how such meetings relate to other types of meetings in the Food and Drug Administration, and the form and content of any agreement reached through a meeting under such paragraph (2); 3

 So in original. The semicolon probably should be a period.

(D)

In carrying out this subsection, the Office shall ensure the consistency and appropriateness 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 regarding 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 Commissioner of Food and Drugs shall consult with the Director of the Office in resolving the substantive dispute.

(F)

The Secretary, acting through the Office, shall review each agreement, guidance, or practice of the Secretary that is specific to the assignment of combination products to agency centers and shall determine whether the agreement, guidance, or practice is consistent with the requirements of this subsection. In carrying out such review, the Secretary shall consult with stakeholders and the directors of the agency centers. After such consultation, the Secretary shall determine whether to continue in effect, modify, revise, or eliminate such agreement, 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 following each agreement, guidance, or practice until continued, modified, revised, or eliminated.

(G)

Not later than one year after October 26, 2002 (except with respect to clause (iv), beginning 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 Office. The report shall include provisions—

(i)

describing the numbers and types of combination products under review and the timeliness in days of such assignments, reviews, and dispute resolutions;

(ii)

identifying the number of premarket reviews of such products that involved a consulting agency center;

(iii)

describing improvements in the consistency of postmarket regulation of combination products; and

(iv)

identifying the percentage of combination products for which a dispute resolution, with respect to premarket review, was requested by the combination product’s sponsor.

(H)

Nothing in this paragraph shall be construed to limit the regulatory authority of any agency center.

(9)

As used in this subsection:

(A)

The term “agency center” means a center 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

 See References in Text note below.

360e, or 360j(g) of this title;

(ii)

a finding of substantial equivalence under this part;

(iii)

approval of a biologics license application 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 “reviews” include all activities of the Food and Drug Administration conducted prior to approval or clearance of an application, notification, 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 article 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 successor regulations); or

(ii)

is a diagnostic agent that improves the visualization of structure or function within the body by increasing the relative difference 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 implant;

(ii)

an article that applies radiation from outside of the body; or

(iii)

the radiation source of an article described 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 construed 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 otherwise 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

 So in original. Probably should be followed by a period.

(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.)

cite as: 21 USC 353