Title 21 CFR reference

The definitions and interpretations of terms in sections 201 and 510 of the Federal Food, Drug, and Cosmetic Act apply to the terms used in this part, if not otherwise defined in this section. The following definitions apply to this part: Active pharmaceutical ingredient means any substance that is intended for incorporation into a finished drug product and is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body. Active pharmaceutical ingredient does not include intermediates used in the synthesis of the substance. Bulk drug substance, as referenced in sections 503A(b)(1)(A) and 503B(a)(2) of the Federal Food, Drug, and Cosmetic Act, means the same as “active pharmaceutical ingredient” as defined in this section. Commercial distribution means any distribution of a human drug, except for investigational use under part 312 of this chapter, and any distribution of an animal drug or an animal feed bearing or containing an animal drug, except for investigational use under part 511 of this chapter. The term does not include internal or…

Except as provided in § 207.13(l), the following classes of persons are exempt from registration and drug listing in accordance with section 510(g) of the Federal Food, Drug, and Cosmetic Act or because FDA has determined, under section 510(g)(5) of the Federal Food, Drug, and Cosmetic Act, that their registration is not necessary for the protection of the public health. This exemption is limited to establishment registration and drug listing requirements and does not relieve a person from other statutory or regulatory obligations. (a)(1) Pharmacies that: (i) Operate in conformance with all applicable local laws regulating the practice of pharmacy and medicine, including all applicable local laws regulating the dispensing of prescription drugs; (ii) Regularly engage in dispensing prescription drugs upon a valid prescription by practitioners licensed by law to administer these drugs to patients under their professional care; and (iii) Do not manufacture, repack, relabel, or salvage drugs other than in the regular course of their business of dispensing or selling drugs at retail. (2) The exemption in this paragraph (a) is limited to pharmacies located in any State as defined in…

(a) Unless exempt under section 510(g) of the Federal Food, Drug, and Cosmetic Act or this part, all manufacturers, repackers, relabelers, and salvagers must register each domestic establishment that manufactures, repacks, relabels, or salvages a drug, or an animal feed bearing or containing a new animal drug, and each foreign establishment that manufactures, repacks, relabels, or salvages a drug, or an animal feed bearing or containing a new animal drug, that is imported or offered for import into the United States. When operations are conducted at more than one establishment and common ownership and control among all the establishments exists, the parent, subsidiary, or affiliate company may submit registration information for all establishments. (b) Private label distributors who do not also manufacture, repack, relabel, or salvage drugs are not required to register under this part. FDA will accept registration or listing information submitted by a private label distributor only if it is acting as an authorized agent for and submitting information that pertains to an establishment that manufactures, repacks, relabels, or salvages drugs.

(a) Registrants must register each domestic establishment no later than 5 calendar days after beginning to manufacture, repack, relabel, or salvage a drug or an animal feed bearing or containing a new animal drug at such establishment. (b) Registrants must register each foreign establishment before a drug or an animal feed bearing or containing a new animal drug manufactured, repacked, relabeled, or salvaged at the establishment is imported or offered for import into the United States.

Registrants must provide the following information: (a) Name of the owner or operator of each establishment; if a partnership, the name of each partner; if a corporation, the name of each corporate officer and director, and the place of incorporation; (b) Each establishment's name, physical address, and telephone number(s); (c) All name(s) of the establishment, including names under which the establishment conducts business or names by which the establishment is known; (d) Registration number of each establishment, if previously assigned by FDA; (e) A Unique Facility Identifier in accordance with the system specified under section 510 of the Federal Food, Drug, and Cosmetic Act. (f) All types of operations performed at each establishment; (g) Name, mailing address, telephone number, and email address of the official contact for the establishment, as provided in § 207.69(a); and (h) Additionally, with respect to foreign establishments subject to registration, the name, mailing address, telephone number, and email address must be provided for: (1) The United States agent, as provided in § 207.69(b); (2) Each importer in the United States of drugs manufactured, repacked,…

Expedited updates.(a) Registrants must update their registration information no later than 30 calendar days after: (1) Closing or selling an establishment; (2) Changing an establishment's name or physical address; or (3) Changing the name, mailing address, telephone number, or email address of the official contact or the United States agent. A registrant, official contact, or United States agent may notify FDA about a change of information for the designated official contact or United States agent, but only a registrant is permitted to designate a new official contact or United States agent. Annual review and update of registration information.(b) Registrants must review and update all registration information required under § 207.25 for each establishment. (1) The first review and update must occur during the period beginning on October 1 and ending December 31 of the year of initial registration, if the initial registration occurs prior to October 1. Subsequent reviews and updates must occur annually, during the period beginning on October 1 and ending December 31 of each calendar year. (2) The updates must reflect all changes that have occurred since the last annual…

Bulk drug substance, as referenced in sections 503A(b)(1)(A) and 503B(a)(2) of the Federal Food, Drug, and Cosmetic Act, previously defined in § 207.3(a)(4), means the same as “active pharmaceutical ingredient” as defined in § 207.1. [81 FR 60212, Aug. 31, 2016, as amended at 86 FR 17061, Apr. 1, 2021]

What is the NDC for a drug and what products must have unique NDCs(a) ? The NDC for a drug is a numeric code. Each finished drug product or unfinished drug subject to the listing requirements of this part must have a unique NDC to identify its labeler, product, and package size and type. What is the format of an NDC(b) ? (1) Except as described in paragraph (b)(4) of this section, the NDC must consist of 10 or 11 digits, divided into three segments as follows: (i) The first segment of the NDC is the labeler code and consists of 4, 5, or 6 digits. The labeler code is assigned by FDA. (ii) The second segment of the NDC is the product code and consists of 3 or 4 digits, as specified in paragraphs (b)(2) and (3) of this section. (iii) The third segment of the NDC is the package code and consists of 1 or 2 digits as specified in paragraphs (b)(2) and (3) of this section. The package code identifies the package size and type of the drug and differentiates between different quantitative and qualitative attributes of the product packaging. (2) The following combinations of labeler code, product code and package code character lengths are permissible: (i) If a labeler code is either…

(a) Once an NDC has been assigned by FDA, the registrant must propose a new and unique NDC for a drug when there is a change, after the drug is initially marketed, to any of the information identified in paragraphs (b) and (c) of this section. A new NDC must be proposed to FDA for assignment through an updated listing in accordance with § 207.57. (b) The proposed new NDC must include a new product code when there is a change to any of the following information: (1) The drug's established name or proprietary name, if any; (2) Any active pharmaceutical ingredient or the strength of any active pharmaceutical ingredient; (3) The dosage form; (4) A change in the drug's status, between prescription and nonprescription, or for animal drugs, between prescription, nonprescription, or veterinary feed directive (VFD) status; (5) A change in the drug's intended use between human and animal; or (6) The drug's distinguishing characteristics such as size, shape, color, code imprint, flavor, and scoring (if any). (c) When there is a change only to the package size or type, including the immediate unit-of-use container, if any, the proposed new NDC must include only a new package code and…

(a) A product may be deemed to be misbranded if an NDC is used: (1) To represent a different drug than the drug for which the NDC has been assigned, as described in § 207.33; (2) To denote or imply FDA approval of a drug; or (3) On products that are not subject to parts 207, 607 of this chapter, or 1271 of this chapter, such as dietary supplements and medical devices. (b) If marketing is resumed for a discontinued drug, and no changes have been made to the drug that would require a new NDC under § 207.35, the drug must have the same NDC that was assigned to it as described in § 207.33, before marketing was discontinued.

(a) Each registrant must list each drug that it manufactures, repacks, relabels, or salvages for commercial distribution. Each domestic registrant must list each such drug regardless of whether the drug enters interstate commerce. When operations are conducted at more than one establishment, and common ownership and control exists among all the establishments, the parent, subsidiary, or affiliate company may submit listing information for any drug manufactured, repacked, relabeled, or salvaged at any such establishment. A drug manufactured, repacked, or relabeled for private label distribution must be listed in accordance with paragraph (c) of this section. (b) Registrants must provide listing information for each drug in accordance with the listing requirements described in §§ 207.49, 207.53, and 207.54 that correspond to the activity or activities they engage in for that drug. (c)(1) For both animal and human drugs, each registrant must list each drug it manufactures, repacks, or relabels for commercial distribution under the trade name or label of a private label distributor using an NDC that includes such private label distributor's labeler code. (2) Additionally, in the…

For each drug being manufactured, repacked, relabeled, or salvaged for commercial distribution at an establishment at the time of initial registration, drug listing information must be submitted no later than 3 calendar days after the initial registration of the establishment.

(a) Each registrant must provide the following listing information for each drug it manufactures for commercial distribution. (1) The appropriate NDC(s), as described in § 207.33, that include all package code variations. In the case of human drugs, the appropriate NDC(s) submitted under this paragraph include the registrant's labeler code. In the case of animal drugs, the appropriate NDC(s) submitted under this paragraph include the registrant's labeler code, except that when the drug is manufactured for commercial distribution under the trade name or label of a private label distributor, the appropriate NDC(s) for animal drugs include the private label distributor's labeler code; (2) Package type and volume information corresponding to the package code segment of the NDC; (3) The listed drug's established name and proprietary name, if any; (4) The name and quantity of each active pharmaceutical ingredient in the listed drug; (5) The name of each inactive ingredient in the listed drug, along with any assertions of confidentiality associated with individual inactive ingredients; (6) The dosage form; (7) The drug's approved U.S. application number, if any; (8) The drug type…

Establishment registration information helps FDA identify who is manufacturing, repacking, relabeling, and salvaging drugs and where those operations are performed. Drug listing information gives FDA a current inventory of drugs manufactured, repacked, relabeled, or salvaged for commercial distribution. Both types of information facilitate implementation and enforcement of the Federal Food, Drug, and Cosmetic Act and are used for many important public health purposes.

Each registrant must provide the following listing information for each drug it repacks or relabels: NDC.(a) The appropriate NDC(s), as described in § 207.33, that include the registrant's labeler code and all package code variations; Source NDC.(b) The NDC assigned to each finished drug received by the registrant for repacking or relabeling, with the exception of medical gases. Each such NDC must be associated with the corresponding NDC(s) for repacked or relabeled drugs, reported under paragraph (a) of this section. Name and Unique Facility Identifier.(c) For each drug identified by an NDC reported under paragraph (a) of this section, the name and Unique Facility Identifier of every establishment where repacking or relabeling is performed for the drug and the type of operation (repacking vs. relabeling) performed at each such establishment. Labeling.(d) For each drug identified by an NDC reported under paragraph (a) of this section, except those human drugs repacked or relabeled exclusively for private label distribution and not distributed under the registrant's own name and label, provide the following: Human prescription drugs.(1) All current labeling for the repacked or…

A registrant who also relabels or repacks a drug that it salvages must list the drug it relabels or repacks in accordance with § 207.53 rather than in accordance with this section. A registrant who performs only salvaging with respect to a drug must provide the following listing information for that drug. (a) The NDC assigned to the drug immediately before the drug is received by the registrant for salvaging; (b) The lot number and expiration date of the salvaged drug product; and (c) The name and Unique Facility Identifier for each establishment where the registrant salvages the drug.

For a particular listed drug, upon our request, the registrant must briefly state the basis for its belief that the drug is not subject to section 505 or 512 of the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act.

Registrants must review and update listing information at a minimum, as follows: (a) Registrants must provide listing information at the time of annual establishment registration for any drug manufactured, repacked, relabeled, or salvaged by them for commercial distribution that has not been listed previously. (b) Registrants must review and update their drug listing information each June and December. When doing so, registrants must: (1)(i) Provide listing information, in accordance with §§ 207.49, 207.53, and 207.54, for any drug manufactured, repacked, relabeled, or salvaged by them for commercial distribution that has not been previously listed; (ii) Submit the date that they discontinued the manufacture, repacking, relabeling or salvaging for commercial distribution of a listed drug and provide the expiration date of the last lot manufactured, repacked, relabeled, or salvaged; (iii) Submit the date that they resumed the manufacture, repacking, or relabeling for commercial distribution of a drug previously discontinued, and provide any required listing information not previously submitted; and (iv) Submit any material changes in any information previously submitted…

Electronic format.(a) (1) Except as provided in § 207.65, all information submitted under this part must be transmitted to FDA in electronic format by using our electronic drug registration and listing system, in a form that we can process, review, and archive. We may periodically issue guidance on how to provide registration and listing information in electronic format (specifying for example method of transmission, media, file formats, preparation, and organization of files). (2) Information provided in electronic format must comply with part 11 of this chapter, except as follows: (i) Advertisements and labeling, including the content of labeling, required under this part are exempt from the requirements in § 11.10(a), (c) through (h), and (k) of this chapter and the corresponding requirements in § 11.30 of this chapter. (ii) All other information submitted under this part is exempt from the requirements in § 11.10(b), (c), and (e) of this chapter and the corresponding requirements in § 11.30 of this chapter. English language.(b) Drug establishment registration and drug listing information must be provided in the English language. The content of labeling must be provided at…

(a) All information submitted under this part must be transmitted to FDA electronically in accordance with § 207.61(a) unless FDA has granted a request for waiver of this requirement prior to the date on which submission of such information is due. Submission of a request for waiver does not excuse timely compliance with the registration and listing requirements. FDA will grant a waiver request if FDA determines that the use of electronic means for submission of registration and listing information is not reasonable for the registrant making the waiver request. (b) Waiver requests under this section must be submitted in writing and must include the specific reasons why electronic submission is not reasonable for the registrant and a U.S. telephone number and mailing address where FDA can contact the registrant. All waiver requests must be sent to: SPL Coordinator, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, Silver Spring, MD 20993. (c) If FDA grants the waiver request, FDA may limit its duration and will specify terms of the waiver and provide information on how to submit establishment registration, drug listings, other information, and updates, as…

Official contact.(a) Registrants subject to the registration requirements of this part must designate an official contact for each establishment. The official contact is responsible for: (1) Ensuring the accuracy of registration and listing information; and (2) Reviewing, disseminating, routing, and responding to all communications from FDA including emergency communications. United States agent.(b) Registrants of foreign establishments subject to this part must designate a single United States agent. The United States agent must reside or maintain a place of business in the United States and may not be a mailbox, answering machine or service, or other place where a person acting as the United States agent is not physically present. The United States agent is responsible for: (1) Reviewing, disseminating, routing, and responding to all communications from FDA including emergency communications; (2) Responding to questions concerning those drugs that are imported or offered for import to the United States; (3) Assisting FDA in scheduling inspections; and (4) If FDA is unable to contact a foreign registrant directly or expeditiously, FDA may provide the information and/or…

(a) Registration of an establishment or listing of a drug does not denote approval of the establishment, the drug, or other drugs of the establishment, nor does it mean that a product may be legally marketed. Any representation that creates an impression of official approval or that a drug is approved or is legally marketable because of registration or listing is misleading and constitutes misbranding. (b) FDA's acceptance of registration and listing information, inclusion of a drug in our database of drugs, or assignment of an NDC does not denote approval of the establishment or the drug or any other drugs of the establishment, nor does it mean that the drug may be legally marketed. Any representation that creates the impression that a drug is approved or is legally marketable because it appears in our database of drugs, has been assigned or displays an NDC, or the establishment has been assigned an establishment registration number or Unique Facility Identifier is misleading and constitutes misbranding. Failure to comply with § 207.37 may also constitute misbranding. (c) Neither registration nor listing constitutes a determination by FDA that a product is a drug as defined by…

(a) Except as provided in paragraphs (b) and (c) of this section, the following information will be available for public disclosure, upon request or at FDA's discretion: (1) All establishment registration information, and (2) After a drug is marketed, information obtained under § 207.33, § 207.49, § 207.53, § 207.54, or § 207.57. (b) Unless such information is publicly available or FDA finds that confidentiality would be inconsistent with protection of the public health, FDA will not make publicly available: (1) Any information submitted under § 207.55 as the basis upon which it has been determined that a particular drug is not subject to section 505 or 512 of the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act, (2) The names of any inactive ingredients submitted under § 207.49(a)(4) for which the registrant makes a valid assertion of confidentiality under § 20.61 of this chapter or other provision of law, or (3) Drug listing information obtained under § 207.33(d)(3), § 207.49(a)(9) and (12), § 207.53(b) and (c), or § 207.54(a) or (c). (c) FDA may determine, in limited circumstances and on a case-by-case basis, that it would be…

(a) Except as provided in paragraph (b) of this section, this part applies to: (1) Domestic manufacturers, domestic repackers, domestic relabelers and domestic salvagers, not exempt under section 510(g) of the Federal Food, Drug, and Cosmetic Act or § 207.13, regardless of whether their drugs enter interstate commerce; (2) Foreign manufacturers, foreign repackers, foreign relabelers and foreign salvagers, not exempt under section 510(g) of the Federal Food, Drug, and Cosmetic Act or § 207.13; (3) Private label distributors, because they must have labeler codes; (4) Establishments engaged in the manufacture, repacking, relabeling, or salvaging of human drugs regulated under a biologics license application (BLA). These establishments are subject to the requirements of this part unless they are required to register and list such drugs as human blood or blood products under part 607 of this chapter and do not engage in activities that would otherwise require them to register and list under this part. (5) Establishments engaged in the manufacture (as defined in § 1271.3(e) of this chapter) of human cells, tissues, and cellular and tissue-based products (HCT/Ps) (as defined in §…