21 U.S.C. § 353b — Outsourcing facilities

Page 179 TITLE 21—FOOD AND DRUGS § 353b stituting, or other such acts that are performed in accordance with directions contained in ap- proved labeling provided by the product’s manu- facturer and other manufacturer directions con- sistent with that labeling. (June 25, 1938, ch. 675, § 503A, as added Pub. L. 105–115, title I, § 127(a), Nov. 21, 1997, 111 Stat. 2328; amended Pub. L. 113–54, title I, § 106(a), Nov. 27, 2013, 127 Stat. 598.) Editorial Notes AMENDMENTS 2013—Subsec. (a). Pub. L. 113–54, § 106(a)(1), struck out ‘‘unsolicited’’ before ‘‘receipt of a valid prescription’’ in introductory provisions. Subsec. (b)(1)(A)(i)(III). Pub. L. 113–54, § 106(a)(4), sub- stituted ‘‘subsection (c)’’ for ‘‘subsection (d)’’. Subsecs. (c) to (f). Pub. L. 113–54, § 106(a)(2), (3), redes- ignated subsecs. (d) to (f) as (c) to (e), respectively, and struck out former subsec. (c). Prior to amendment, sub- sec. (c) read as follows: ‘‘A drug may be compounded under subsection (a) of this section only if the phar- macy, licensed pharmacist, or licensed physician does not advertise or promote the compounding of any par- ticular drug, class of drug, or type of drug. The phar- macy, licensed pharmacist, or licensed physician may advertise and promote the compounding service pro- vided by the licensed pharmacist or licensed physi- cian.’’ Statutory Notes and Related Subsidiaries EFFECTIVE DATE Pub. L. 105–115, title I, § 127(b), Nov. 21, 1997, 111 Stat. 2330, provided that: ‘‘Section 503A of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 353a], added by sub- section (a), shall take effect upon the expiration of the 1-year period beginning on the date of the enactment of this Act [Nov. 21, 1997].’’ § 353a–1. Enhanced communication (a) Submissions from State boards of pharmacy In a manner specified by the Secretary of Health and Human Services (referred to in this section as the ‘‘Secretary’’), the Secretary shall receive submissions from State boards of phar- macy— (1) describing actions taken against compounding pharmacies, as described in sub- section (b); or (2) expressing concerns that a compounding pharmacy may be acting contrary to section 353a of this title. (b) Content of submissions from State boards of pharmacy An action referred to in subsection (a)(1) is, with respect to a pharmacy that compounds drugs, any of the following: (1) The issuance of a warning letter, or the imposition of sanctions or penalties, by a State for violations of a State’s pharmacy reg- ulations pertaining to compounding. (2) The suspension or revocation of a State- issued pharmacy license or registration for violations of a State’s pharmacy regulations pertaining to compounding. (3) The recall of a compounded drug due to concerns relating to the quality or purity of such drug. (c) Consultation The Secretary shall implement subsection (a) in consultation with the National Association of Boards of Pharmacy. (d) Notifying State boards of pharmacy The Secretary shall immediately notify State boards of pharmacy when— (1) the Secretary receives a submission under subsection (a)(1); or (2) the Secretary makes a determination that a pharmacy is acting contrary to section 353a of this title. (Pub. L. 113–54, title I, § 105, Nov. 27, 2013, 127 Stat. 597.) Editorial Notes CODIFICATION Section was enacted as part of the Compounding Quality Act and also as part of the Drug Quality and Security Act, and not as part of the Federal Food, Drug, and Cosmetic Act which comprises this chapter. § 353b. Outsourcing facilities (a) In general Sections 352(f)(1), 355, and 360eee–1 of this title shall not apply to a drug compounded by or under the direct supervision of a licensed phar- macist in a facility that elects to register as an outsourcing facility if each of the following con- ditions is met: (1) Registration and reporting The drug is compounded in an outsourcing facility that is in compliance with the require- ments of subsection (b). (2) Bulk drug substances The drug is compounded in an outsourcing facility that does not compound using bulk drug substances (as defined in section 207.3(a)(4) of title 21, Code of Federal Regula- tions (or any successor regulation)), unless— (A)(i) the bulk drug substance appears on a list established by the Secretary identifying bulk drug substances for which there is a clinical need, by— (I) publishing a notice in the Federal Register proposing bulk drug substances to be included on the list, including the ra- tionale for such proposal; (II) providing a period of not less than 60 calendar days for comment on the notice; and (III) publishing a notice in the Federal Register designating bulk drug substances for inclusion on the list; or (ii) the drug compounded from such bulk drug substance appears on the drug shortage list in effect under section 356e of this title at the time of compounding, distribution, and dispensing; (B) if an applicable monograph exists under the United States Pharmacopeia, the National Formulary, or another compen- dium or pharmacopeia recognized by the Secretary for purposes of this paragraph, the bulk drug substances each comply with the monograph; (C) the bulk drug substances are each man- ufactured by an establishment that is reg- istered under section 360 of this title (includ- ing a foreign establishment that is reg- istered under section 360(i) of this title); and Page 180 TITLE 21—FOOD AND DRUGS § 353b (D) the bulk drug substances are each ac- companied by a valid certificate of analysis. (3) Ingredients (other than bulk drug sub- stances) If any ingredients (other than bulk drug sub- stances) are used in compounding the drug, such ingredients comply with the standards of the applicable United States Pharmacopeia or National Formulary monograph, if such mono- graph exists, or of another compendium or pharmacopeia recognized by the Secretary for purposes of this paragraph if any. (4) Drugs withdrawn or removed because un- safe or not effective The drug does not appear on a list published by the Secretary of drugs that have been with- drawn or removed from the market because such drugs or components of such drugs have been found to be unsafe or not effective. (5) Essentially a copy of an approved drug The drug is not essentially a copy of one or more approved drugs. (6) Drugs presenting demonstrable difficulties for compounding The drug— (A) is not identified (directly or as part of a category of drugs) on a list published by the Secretary, through the process described in subsection (c), of drugs or categories of drugs that present demonstrable difficulties for compounding that are reasonably likely to lead to an adverse effect on the safety or effectiveness of the drug or category of drugs, taking into account the risks and benefits to patients; or (B) is compounded in accordance with all applicable conditions identified on the list described in subparagraph (A) as conditions that are necessary to prevent the drug or category of drugs from presenting the de- monstrable difficulties described in subpara- graph (A). (7) Elements to assure safe use In the case of a drug that is compounded from a drug that is the subject of a risk eval- uation and mitigation strategy approved with elements to assure safe use pursuant to sec- tion 355–1 of this title, or from a bulk drug substance that is a component of such drug, the outsourcing facility demonstrates to the Secretary prior to beginning compounding that such facility will utilize controls com- parable to the controls applicable under the relevant risk evaluation and mitigation strat- egy. (8) Prohibition on wholesaling The drug will not be sold or transferred by an entity other than the outsourcing facility that compounded such drug. This paragraph does not prohibit administration of a drug in a health care setting or dispensing a drug pur- suant to a prescription executed in accordance with section 353(b)(1) of this title. (9) Fees The drug is compounded in an outsourcing facility that has paid all fees owed by such fa- cility pursuant to section 379j–62 of this title. (10) Labeling of drugs (A) Label The label of the drug includes— (i) the statement ‘‘This is a compounded drug.’’ or a reasonable comparable alter- native statement (as specified by the Sec- retary) that prominently identifies the drug as a compounded drug; (ii) the name, address, and phone number of the applicable outsourcing facility; and (iii) with respect to the drug— (I) the lot or batch number; (II) the established name of the drug; (III) the dosage form and strength; (IV) the statement of quantity or vol- ume, as appropriate; (V) the date that the drug was com- pounded; (VI) the expiration date; (VII) storage and handling instruc- tions; (VIII) the National Drug Code number, if available; (IX) the statement ‘‘Not for resale’’, and, if the drug is dispensed or distrib- uted other than pursuant to a prescrip- tion for an individual identified patient, the statement ‘‘Office Use Only’’; and (X) subject to subparagraph (B)(i), a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingre- dient. (B) Container The container from which the individual units of the drug are removed for dispensing or for administration (such as a plastic bag containing individual product syringes) shall include— (i) the information described under sub- paragraph (A)(iii)(X), if there is not space on the label for such information; (ii) the following information to facili- tate adverse event reporting: www.fda.gov/ medwatch and 1–800–FDA–1088 (or any suc- cessor Internet Web site or phone number); and (iii) directions for use, including, as ap- propriate, dosage and administration. (C) Additional information The label and labeling of the drug shall in- clude any other information as determined necessary and specified in regulations pro- mulgated by the Secretary. (11) Outsourcing facility requirement The drug is compounded in an outsourcing facility in which the compounding of drugs oc- curs only in accordance with this section. (b) Registration of outsourcing facilities and re- porting of drugs (1) Registration of outsourcing facilities (A) Annual registration Upon electing and in order to become an outsourcing facility, and during the period beginning on October 1 and ending on De- cember 31 of each year thereafter, a facil- ity— Page 181 TITLE 21—FOOD AND DRUGS § 353b (i) shall register with the Secretary its name, place of business, and unique facil- ity identifier (which shall conform to the requirements for the unique facility iden- tifier established under section 360 of this title), and a point of contact email ad- dress; and (ii) shall indicate whether the outsourcing facility intends to compound a drug that appears on the list in effect under section 356e of this title during the subsequent calendar year. (B) Availability of registration for inspection; list (i) Registrations The Secretary shall make available for inspection, to any person so requesting, any registration filed pursuant to this paragraph. (ii) List The Secretary shall make available on the public Internet Web site of the Food and Drug Administration a list of the name of each facility registered under this subsection as an outsourcing facility, the State in which each such facility is lo- cated, whether the facility compounds from bulk drug substances, and whether any such compounding from bulk drug sub- stances is for sterile or nonsterile drugs. (2) Drug reporting by outsourcing facilities (A) In general Upon initially registering as an outsourcing facility, once during the month of June of each year, and once during the month of December of each year, each outsourcing facility that registers with the Secretary under paragraph (1) shall submit to the Secretary a report— (i) identifying the drugs compounded by such outsourcing facility during the pre- vious 6-month period; and (ii) with respect to each drug identified under clause (i), providing the active in- gredient, the source of such active ingre- dient, the National Drug Code number of the source drug or bulk active ingredient, if available, the strength of the active in- gredient per unit, the dosage form and route of administration, the package de- scription, the number of individual units produced, and the National Drug Code number of the final product, if assigned. (B) Form Each report under subparagraph (A) shall be prepared in such form and manner as the Secretary may prescribe by regulation or guidance. (C) Confidentiality Reports submitted under this paragraph shall be exempt from inspection under para- graph (1)(B)(i), unless the Secretary finds that such an exemption would be incon- sistent with the protection of the public health. (3) Electronic registration and reporting Registrations and drug reporting under this subsection (including the submission of up- dated information) shall be submitted to the Secretary by electronic means unless the Sec- retary grants a request for waiver of such re- quirement because use of electronic means is not reasonable for the person requesting waiv- er. (4) Risk-based inspection frequency (A) In general Outsourcing facilities— (i) shall be subject to inspection pursu- ant to section 374 of this title; and (ii) shall not be eligible for the exemp- tion under section 374(a)(2)(A) of this title. (B) Risk-based schedule The Secretary, acting through one or more officers or employees duly designated by the Secretary, shall inspect outsourcing facili- ties in accordance with a risk-based schedule established by the Secretary. (C) Risk factors In establishing the risk-based schedule, the Secretary shall inspect outsourcing fa- cilities according to the known safety risks of such outsourcing facilities, which shall be based on the following factors: (i) The compliance history of the outsourcing facility. (ii) The record, history, and nature of re- calls linked to the outsourcing facility. (iii) The inherent risk of the drugs com- pounded at the outsourcing facility. (iv) The inspection frequency and his- tory of the outsourcing facility, including whether the outsourcing facility has been inspected pursuant to section 374 of this title within the last 4 years. (v) Whether the outsourcing facility has registered under this paragraph as an enti- ty that intends to compound a drug that appears on the list in effect under section 356e of this title. (vi) Any other criteria deemed necessary and appropriate by the Secretary for pur- poses of allocating inspection resources. (5) Adverse event reporting Outsourcing facilities shall submit adverse event reports to the Secretary in accordance with the content and format requirements es- tablished through guidance or regulation under section 310.305 of title 21, Code of Fed- eral Regulations (or any successor regula- tions). (c) Regulations (1) In general The Secretary shall implement the list de- scribed in subsection (a)(6) through regula- tions. (2) Advisory committee on compounding Before issuing regulations to implement sub- section (a)(6), the Secretary shall convene and consult an advisory committee on compounding. The advisory committee shall include representatives from the National As- sociation of Boards of Pharmacy, the United States Pharmacopeia, pharmacists with cur- rent experience and expertise in compounding, Page 182 TITLE 21—FOOD AND DRUGS § 353c 1 So in original. 2 So in original. Two subsecs. (d) have been enacted. physicians with background and knowledge in compounding, and patient and public health advocacy organizations. (3) Interim list (A) In general Before the effective date of the regulations finalized to implement subsection (a)(6), the Secretary may designate drugs, categories of drugs, or conditions as described such 1 sub- section by— (i) publishing a notice of such sub- stances, drugs, categories of drugs, or con- ditions proposed for designation, including the rationale for such designation, in the Federal Register; (ii) providing a period of not less than 60 calendar days for comment on the notice; and (iii) publishing a notice in the Federal Register designating such drugs, cat- egories of drugs, or conditions. (B) Sunset of notice Any notice provided under subparagraph (A) shall not be effective after the earlier of— (i) the date that is 5 years after Novem- ber 27, 2013; or (ii) the effective date of the final regula- tions issued to implement subsection (a)(6). (4) Updates The Secretary shall review, and update as necessary, the regulations containing the lists of drugs, categories of drugs, or conditions de- scribed in subsection (a)(6) regularly, but not less than once every 4 years. Nothing in the previous sentence prohibits submissions to the Secretary, before or during any 4-year period described in such sentence, requesting updates to such lists. (d) 2 Definitions In this section: (1) The term ‘‘compounding’’ includes the combining, admixing, mixing, diluting, pool- ing, reconstituting, or otherwise altering of a drug or bulk drug substance to create a drug. (2) The term ‘‘essentially a copy of an ap- proved drug’’ means— (A) a drug that is identical or nearly iden- tical to an approved drug, or a marketed drug not subject to section 353(b) of this title and not subject to approval in an application submitted under section 355 of this title, un- less, in the case of an approved drug, the drug appears on the drug shortage list in ef- fect under section 356e of this title at the time of compounding, distribution, and dis- pensing; or (B) a drug, a component of which is a bulk drug substance that is a component of an ap- proved drug or a marketed drug that is not subject to section 353(b) of this title and not subject to approval in an application sub- mitted under section 355 of this title, unless there is a change that produces for an indi- vidual patient a clinical difference, as deter- mined by the prescribing practitioner, be- tween the compounded drug and the com- parable approved drug. (3) The term ‘‘approved drug’’ means a drug that is approved under section 355 of this title and does not appear on the list described in subsection (a)(4) of drugs that have been with- drawn or removed from the market because such drugs or components of such drugs have been found to be unsafe or not effective. (4)(A) The term ‘‘outsourcing facility’’ means a facility at one geographic location or address that— (i) is engaged in the compounding of ster- ile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. (B) An outsourcing facility is not required to be a licensed pharmacy. (C) An outsourcing facility may or may not obtain prescriptions for identified individual patients. (5) The term ‘‘sterile drug’’ means a drug that is intended for parenteral administration, an ophthalmic or oral inhalation drug in aque- ous format, or a drug that is required to be sterile under Federal or State law. (d) 2 Obligation to pay fees Payment of the fee under section 379j–62 of this title, as described in subsection (a)(9), shall not relieve an outsourcing facility that is li- censed as a pharmacy in any State that requires pharmacy licensing fees of its obligation to pay such State fees. (June 25, 1938, ch. 675, § 503B, as added Pub. L. 113–54, title I, § 102(a)(2), Nov. 27, 2013, 127 Stat. 588.) Editorial Notes PRIOR PROVISIONS A prior section 503B of act June 25, 1938, ch. 675, was renumbered section 503C by Pub. L. 113–54, § 102(a)(1), Nov. 27, 2013, 127 Stat. 587, and transferred to section 353c of this title. § 353c. Prereview of television advertisements (a) In general The Secretary may require the submission of any television advertisement for a drug (includ- ing any script, story board, rough, or a com- pleted video production of the television adver- tisement) to the Secretary for review under this section not later than 45 days before dissemina- tion of the television advertisement. (b) Review In conducting a review of a television adver- tisement under this section, the Secretary may make recommendations with respect to informa- tion included in the label of the drug— (1) on changes that are— (A) necessary to protect the consumer good and well-being; or (B) consistent with prescribing informa- tion for the product under review; and