cfr_sections
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| section_id ▼ | title_number | title_name | chapter | subchapter | part_number | part_name | subpart | subpart_name | section_number | section_heading | agency | authority | source_citation | amendment_citations | full_text |
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| 21:21:5.0.1.1.4.1.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | A | Subpart A—General Provisions | § 314.1 Scope of this part. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 57 FR 17981, Apr. 28, 1992; 64 FR 401, Jan. 5, 1999; 89 FR 51782, June 18, 2024] | (a) This part sets forth procedures and requirements for the submission to, and the review by, the Food and Drug Administration of applications and abbreviated applications to market a new drug under section 505 of the Federal Food, Drug, and Cosmetic Act, as well as amendments, supplements, and postmarketing reports to them. (b) This part does not apply to drug products subject to licensing by FDA under the Public Health Service Act (58 Stat. 632 as amended (42 U.S.C. 201 et seq. )) and subchapter F of chapter I of title 21 of the Code of Federal Regulations. (c) The following provisions do not apply to designated medical gases, which are subject to the certification and postmarketing reporting requirements under part 230 of this chapter: (1) Sections 314.50 through 314.72; (2) Section 314.80; (3) Section 314.81, except paragraph (b)(3); (4) Section 314.90; (5) Subpart C of this part; (6) Sections 314.100 through 314.162; (7) Subpart H of this part; and (8) Subpart I of this part. (d) References in this part to regulations in the Code of Federal Regulations are to chapter I of title 21, unless otherwise noted. | |||
| 21:21:5.0.1.1.4.1.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | A | Subpart A—General Provisions | § 314.2 Purpose. | FDA | The purpose of this part is to establish an efficient and thorough drug review process in order to: (a) Facilitate the approval of drugs shown to be safe and effective; and (b) ensure the disapproval of drugs not shown to be safe and effective. These regulations are also intended to establish an effective system for FDA's surveillance of marketed drugs. These regulations shall be construed in light of these objectives. | ||||
| 21:21:5.0.1.1.4.1.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | A | Subpart A—General Provisions | § 314.3 Definitions. | FDA | [81 FR 69636, Oct. 6, 2016] | (a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter. (b) The following definitions of terms apply to this part and part 320 of this chapter: 180-day exclusivity period is the 180-day period beginning on the date of the first commercial marketing of the drug (including the commercial marketing of the reference listed drug) by any first applicant. The 180-day period ends on the day before the date on which an ANDA submitted by an applicant other than a first applicant could be approved. 505(b)(2) application is an NDA submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act for a drug for which at least some of the investigations described in section 505(b)(1)(A) of the Federal Food, Drug, and Cosmetic Act and relied upon by the applicant for approval of the NDA were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted. Abbreviated application, abbreviated new drug application, or ANDA is the application described under § 314.94, including all amendments and supplements to the application. Acknowledgment letter is a written, postmarked communication from FDA to an applicant stating that the Agency has determined that an ANDA is sufficiently complete to permit a substantive review. An acknowledgment letter indicates that the ANDA is regarded as received. Act is the Federal Food, Drug, and Cosmetic Act (section 201 et seq. (21 U.S.C. 301 et seq. )). Active ingredient is any component that 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 of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in t… | |||
| 21:21:5.0.1.1.4.2.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.50 Content and format of an NDA. | FDA | [50 FR 7493, Feb. 22, 1985] | NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical entity will generally contain an application form, an index, a summary, five or six technical sections, case report tabulations of patient data, case report forms, drug samples, and labeling, including, if applicable, any Medication Guide required under part 208 of this chapter. Other NDAs will generally contain only some of those items, and information will be limited to that needed to support the particular submission. These include an NDA of the type described in section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, an amendment, and a supplement. The NDA is required to contain reports of all investigations of the drug product sponsored by the applicant, and all other information about the drug pertinent to an evaluation of the NDA that is received or otherwise obtained by the applicant from any source. FDA will maintain guidance documents on the format and content of NDAs to assist applicants in their preparation. (a) Application form. The applicant must submit a completed and signed application form that contains the following: (1) The name and address of the applicant; the date of the NDA; the NDA number if previously issued (for example, if the NDA is a resubmission or an amendment or supplement); the name of the drug product, including its established, proprietary, code, and chemical names; the dosage form and strength; the route of administration; the identification numbers of all INDs (as defined in § 312.3(b) of this chapter) that are referenced in the NDA; the identification numbers of all drug master files and other applications under this part that are referenced in the NDA; and the drug product's proposed indications for use. (2) A statement whether the submission is an original submission, a… | |||
| 21:21:5.0.1.1.4.2.1.10 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.71 Procedures for submission of a supplement to an approved application. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 58 FR 47352, Sept. 8, 1993; 67 FR 9586, Mar. 4, 2002; 73 FR 39609, July 10, 2008] | (a) Only the applicant may submit a supplement to an application. (b) All procedures and actions that apply to an application under § 314.50 also apply to supplements, except that the information required in the supplement is limited to that needed to support the change. A supplement is required to contain an archival copy and a review copy that include an application form and appropriate technical sections, samples, and labeling; except that a supplement for a change other than a change in labeling is required also to contain a field copy. (c) All procedures and actions that apply to applications under this part, including actions by applicants and the Food and Drug Administration, also apply to supplements except as specified otherwise in this part. | |||
| 21:21:5.0.1.1.4.2.1.11 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.72 Change in ownership of an application. | FDA | [50 FR 7493, Feb. 22, 1985; 50 FR 14212, Apr. 11, 1985, as amended at 50 FR 21238, May 23, 1985; 67 FR 9586, Mar. 4, 2002; 68 FR 25287, May 12, 2003] | (a) An applicant may transfer ownership of its application. At the time of transfer the new and former owners are required to submit information to the Food and Drug Administration as follows: (1) The former owner shall submit a letter or other document that states that all rights to the application have been transferred to the new owner. (2) The new owner shall submit an application form signed by the new owner and a letter or other document containing the following: (i) The new owner's commitment to agreements, promises, and conditions made by the former owner and contained in the application; (ii) The date that the change in ownership is effective; and (iii) Either a statement that the new owner has a complete copy of the approved application, including supplements and records that are required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public information regulations. (b) The new owner shall advise FDA about any change in the conditions in the approved application under § 314.70, except the new owner may advise FDA in the next annual report about a change in the drug product's label or labeling to change the product's brand or the name of its manufacturer, packer, or distributor. | |||
| 21:21:5.0.1.1.4.2.1.12 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.80 Postmarketing reporting of adverse drug experiences. | FDA | [50 FR 7493, Feb. 22, 1985; 50 FR 14212, Apr. 11, 1985, as amended at 50 FR 21238, May 23, 1985; 51 FR 24481, July 3, 1986; 52 FR 37936, Oct. 13, 1987; 55 FR 11580, Mar. 29, 1990; 57 FR 17983, Apr. 28, 1992; 62 FR 34168, June 25, 1997; 62 FR 52251, Oct. 7, 1997; 63 FR 14611, Mar. 26, 1998; 67 FR 9586, Mar. 4, 2002; 69 FR 13473, Mar. 23, 2004; 74 FR 13113, Mar. 26, 2009; 79 FR 33088, June 10, 2014] | (a) Definitions. The following definitions of terms apply to this section: Adverse drug experience. Any adverse event associated with the use of a drug in humans, whether or not considered drug related, including the following: An adverse event occurring in the course of the use of a drug product in professional practice; an adverse event occurring from drug overdose whether accidental or intentional; an adverse event occurring from drug abuse; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action. Individual case safety report (ICSR). A description of an adverse drug experience related to an individual patient or subject. ICSR attachments. Documents related to the adverse drug experience described in an ICSR, such as medical records, hospital discharge summaries, or other documentation. Disability. A substantial disruption of a person's ability to conduct normal life functions. Life-threatening adverse drug experience. Any adverse drug experience that places the patient, in the view of the initial reporter, at immediate risk of death from the adverse drug experience as it occurred, i.e. , it does not include an adverse drug experience that, had it occurred in a more severe form, might have caused death. Serious adverse drug experience. Any adverse drug experience occurring at any dose that results in any of the following outcomes: Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requir… | |||
| 21:21:5.0.1.1.4.2.1.13 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.81 Other postmarketing reports. | FDA | [50 FR 7493, Feb. 22, 1985; 50 FR 14212, Apr. 11, 1985, as amended at 50 FR 21238, May 23, 1985; 55 FR 11580, Mar. 29, 1990; 57 FR 17983, Apr. 28, 1992; 63 FR 66670, Dec. 2, 1998; 64 FR 401, Jan. 5, 1999; 65 FR 64617, Oct. 30, 2000; 66 FR 10815, Feb. 20, 2001; 68 FR 69019, Dec. 11, 2003; 69 FR 18766, Apr. 8, 2004; 69 FR 48775, Aug. 11, 2004; 72 FR 58999, Oct. 18, 2007; 74 FR 13113, Mar. 26, 2009; 74 FR 37167, July 28, 2009; 76 FR 78539, Dec. 19, 2011; 80 FR 38938, July 8, 2015; 81 FR 60221, Aug. 31, 2016; 89 FR 105331, Dec. 26, 2024] | (a) Applicability. Each applicant shall make the reports for each of its approved applications and abbreviated applications required under this section and section 505(k) of the act. (b) Reporting requirements. The applicant shall submit to the Food and Drug Administration at the specified times two copies of the following reports: (1) NDA—Field alert report. The applicant shall submit information of the following kinds about distributed drug products and articles to the FDA district office that is responsible for the facility involved within 3 working days of receipt by the applicant. The information may be provided by telephone or other rapid communication means, with prompt written followup. The report and its mailing cover should be plainly marked: “NDA—Field Alert Report.” (i) Information concerning any incident that causes the drug product or its labeling to be mistaken for, or applied to, another article. (ii) Information concerning any bacteriological contamination, or any significant chemical, physical, or other change or deterioration in the distributed drug product, or any failure of one or more distributed batches of the drug product to meet the specification established for it in the application. (2) Annual report. The applicant shall submit each year within 60 days of the anniversary date of U.S. approval of the application, two copies of the report to the FDA division responsible for reviewing the application. Each annual report is required to be accompanied by a completed transmittal Form FDA 2252 (Transmittal of Periodic Reports for Drugs for Human Use), and must include all the information required under this section that the applicant received or otherwise obtained during the annual reporting interval that ends on the U.S. anniversary date. The report is required to contain in the order listed: (i) Summary. A brief summary of significant new information from the previous year that might affect the safety, effectiveness, or labeling of the drug product. The report is also require… | |||
| 21:21:5.0.1.1.4.2.1.14 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.90 Waivers. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 67 FR 9586, Mar. 4, 2002; 81 FR 69649, Oct. 6, 2016] | (a) An applicant may ask the Food and Drug Administration to waive under this section any requirement that applies to the applicant under §§ 314.50 through 314.81. An applicant may ask FDA to waive under § 314.126(c) any criteria of an adequate and well-controlled study described in § 314.126(b). A waiver request under this section is required to be submitted with supporting documentation in an NDA, or in an amendment or supplement to an NDA. The waiver request is required to contain one of the following: (1) An explanation why the applicant's compliance with the requirement is unnecessary or cannot be achieved; (2) A description of an alternative submission that satisfies the purpose of the requirement; or (3) Other information justifying a waiver. (b) FDA may grant a waiver if it finds one of the following: (1) The applicant's compliance with the requirement is unnecessary for the agency to evaluate the NDA or compliance cannot be achieved; (2) The applicant's alternative submission satisfies the requirement; or (3) The applicant's submission otherwise justifies a waiver. (c) If FDA grants the applicant's waiver request with respect to a requirement under §§ 314.50 through 314.81, the waived requirement will not constitute a basis for refusal to approve an NDA under § 314.125. | |||
| 21:21:5.0.1.1.4.2.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.52 Notice of certification of invalidity, unenforceability, or noninfringement of a patent. | FDA | [81 FR 69641, Oct. 6, 2016, as amended at 84 FR 6673, Feb. 28, 2019] | (a) Notice of certification. For each patent that claims the listed drug or drugs relied upon or that claims a use for such listed drug or drugs and for which the 505(b)(2) applicant submits a paragraph IV certification, the applicant must send notice of such certification by registered or certified mail, return receipt requested, or by a designated delivery service, as defined in paragraph (g) of this section, to each of the following persons: (1) Each owner of the patent that is the subject of the certification or the representative designated by the owner to receive the notice. The name and address of the patent owner or its representative may be obtained from the U.S. Patent and Trademark Office; and (2) The holder of the approved NDA under section 505(b) of the Federal Food, Drug, and Cosmetic Act for each drug product which is claimed by the patent or a use of which is claimed by the patent and for which the applicant is seeking approval, or, if the NDA holder does not reside or maintain a place of business within the United States, the NDA holder's attorney, agent, or other authorized official. The name and address of the NDA holder or its attorney, agent, or authorized official may be obtained by sending a written or electronic communication to the Central Document Room, Attn: Orange Book Staff, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266, or to the Orange Book Staff at the email address listed on the Agency's Web site at http://www.fda.gov. (3) This paragraph (a) does not apply to a method-of-use patent that does not claim a use for which the applicant is seeking approval. (4) An applicant may send notice by an alternative method only if FDA has agreed in advance that the method will produce an acceptable form of documentation. (b) Sending the notice. (1) Except as provided under paragraph (d) of this section, the applicant must send the notice required by paragraph (a) of this section on or after the date of filing desc… | |||
| 21:21:5.0.1.1.4.2.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.53 Submission of patent information. | FDA | [81 FR 69643, Oct. 6, 2016, as amended at 84 FR 6673, Feb. 28, 2019] | (a) Who must submit patent information. This section applies to any applicant who submits to FDA an NDA or an amendment to it under section 505(b) of the Federal Food, Drug, and Cosmetic Act and § 314.50 or a supplement to an approved NDA under § 314.70, except as provided in paragraph (d)(2) of this section. (b) Patents for which information must be submitted and patents for which information must not be submitted —(1) General requirements. An applicant described in paragraph (a) of this section must submit to its NDA the required information, on the required FDA declaration form, set forth in paragraph (c) of this section for each patent that claims the drug or a method of using the drug that is the subject of the NDA or amendment or supplement to it and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner of the patent engaged in the manufacture, use, or sale of the drug product. For purposes of this part, such patents consist of drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method-of-use patents. For patents that claim the drug substance, the applicant must submit information only on those patents that claim the drug substance that is the subject of the pending or approved NDA or that claim a drug substance that is the same as the active ingredient that is the subject of the approved or pending NDA. For patents that claim only a polymorph that is the same as the active ingredient described in the approved or pending NDA, the applicant must certify in the required FDA declaration form that the applicant has test data, as set forth in paragraph (b)(2) of this section, demonstrating that a drug product containing the polymorph will perform the same as the drug product described in the NDA. For patents that claim a drug product, the applicant must submit information only on those patents that claim the drug product, as is defined in § 314.3, that is described in the pending or approved ND… | |||
| 21:21:5.0.1.1.4.2.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.54 Procedure for submission of a 505(b)(2) application requiring investigations for approval of a new indication for, or other change from, a listed drug. | FDA | [57 FR 17982, Apr. 28, 1992; 57 FR 61612, Dec. 28, 1992, as amended at 58 FR 47351, Sept. 8, 1993; 59 FR 50364, Oct. 3, 1994; 81 FR 69647, Oct. 6, 2016] | (a) The Federal Food, Drug, and Cosmetic Act does not permit approval of an ANDA for a new indication, nor does it permit approval of other changes in a listed drug if investigations, other than bioavailability or bioequivalence studies, are essential to the approval of the change. Any person seeking approval of a drug product that represents a modification of a listed drug (e.g., a new indication or new dosage form) and for which investigations, other than bioavailability or bioequivalence studies, are essential to the approval of the changes may, except as provided in paragraph (b) of this section, submit a 505(b)(2) application. This 505(b)(2) application need contain only that information needed to support the modification(s) of the listed drug. (1) The applicant must submit a complete archival copy of the application that contains the following: (i) The information required under § 314.50(a), (b), (c), (d)(1), (d)(3), (e), and (g), except that § 314.50(d)(1)(ii)( c ) must contain the proposed or actual master production record, including a description of the equipment, to be used for the manufacture of a commercial lot of the drug product. (ii) The information required under § 314.50 (d)(2), (d)(4) (if an anti-infective drug), (d)(5), (d)(6), and (f) as needed to support the safety and effectiveness of the drug product. (iii) Identification of each listed drug for which FDA has made a finding of safety and effectiveness and on which finding the applicant relies in seeking approval of its proposed drug product by established name, if any, proprietary name, dosage form, strength, route of administration, name of listed drug's application holder, and listed drug's approved NDA number. The listed drug(s) identified as relied upon must include a drug product approved in an NDA that: (A) Is pharmaceutically equivalent to the drug product for which the original 505(b)(2) application is submitted; and (B) Was approved before the original 505(b)(2) application was submitted. (iv) If the applicant is seeking ap… | |||
| 21:21:5.0.1.1.4.2.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.55 Pediatric use information. | FDA | [63 FR 66670, Dec. 2, 1998] | (a) Required assessment. Except as provided in paragraphs (b), (c), and (d) of this section, each application for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration shall contain data that are adequate to assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective. Where the course of the disease and the effects of the drug are sufficiently similar in adults and pediatric patients, FDA may conclude that pediatric effectiveness can be extrapolated from adequate and well-controlled studies in adults usually supplemented with other information obtained in pediatric patients, such as pharmacokinetic studies. Studies may not be needed in each pediatric age group, if data from one age group can be extrapolated to another. Assessments of safety and effectiveness required under this section for a drug product that represents a meaningful therapeutic benefit over existing treatments for pediatric patients must be carried out using appropriate formulations for each age group(s) for which the assessment is required. (b) Deferred submission. (1) FDA may, on its own initiative or at the request of an applicant, defer submission of some or all assessments of safety and effectiveness described in paragraph (a) of this section until after approval of the drug product for use in adults. Deferral may be granted if, among other reasons, the drug is ready for approval in adults before studies in pediatric patients are complete, or pediatric studies should be delayed until additional safety or effectiveness data have been collected. If an applicant requests deferred submission, the request must provide a certification from the applicant of the grounds for delaying pediatric studies, a description of the planned or ongoing studies, and evidence that the studies are being or will be conducted wit… | |||
| 21:21:5.0.1.1.4.2.1.6 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.56 Nonprescription drug product with an additional condition for nonprescription use (ACNU). | FDA | [89 FR 105330, Dec. 26, 2024] | (a) Definition. The following definition applies to this section: (1) Additional condition for nonprescription use (ACNU) means one or more FDA-approved conditions that an applicant of a nonprescription drug product must implement to ensure consumers' appropriate self-selection or appropriate actual use, or both, of the nonprescription drug product without the supervision of a practitioner licensed by law to administer such drug if an applicant demonstrates and FDA determines that labeling alone is insufficient to ensure appropriate self-selection or appropriate actual use, or both. (2) [Reserved] (b) Separate application required for a nonprescription drug product with an ACNU . Notwithstanding § 310.200(b) of this chapter, an applicant must submit a separate application for a nonprescription drug product with an ACNU. Initial approval for a nonprescription drug product with an ACNU cannot be obtained through a supplement to an approved application. (c) Specific requirements for an application for a nonprescription drug product with an ACNU. The applicant must submit an application that complies with the following requirements: (1) New drug application (NDA). When fulfilling the content and format requirements under § 314.50, an NDA for a nonprescription drug product with an ACNU must include— (i) A statement regarding whether the purpose of the ACNU is to ensure appropriate self-selection or appropriate actual use, or both, by consumers of the nonprescription drug product with an ACNU without the supervision of a practitioner licensed by law to administer such drug; (ii) A statement regarding the necessity of the ACNU; (iii) A description of how the ACNU ensures appropriate self-selection or appropriate actual use, or both; (iv) A description of the key elements of the ACNU, including: (A) The additional condition implemented by the applicant to be fulfilled by the consumer to obtain the nonprescription drug product with an ACNU; (B) The labeling specifically associated with the ACNU; and (… | |||
| 21:21:5.0.1.1.4.2.1.7 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.60 Amendments to an unapproved NDA, supplement, or resubmission. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 57 FR 17983, Apr. 28, 1992; 58 FR 47352, Sept. 8, 1993; 63 FR 5252, Feb. 2, 1998; 69 FR 18764, Apr. 8, 2004; 73 FR 39608, July 10, 2008; 81 FR 69648, Oct. 6, 2016] | (a) Submission of NDA. FDA generally assumes that when an original NDA, supplement to an approved NDA, or resubmission of an NDA or supplement is submitted to the Agency for review, the applicant believes that the Agency can approve the NDA, supplement, or resubmission as submitted. However, the applicant may submit an amendment to an NDA, supplement, or resubmission that has been filed under § 314.101 but is not yet approved. (b) Submission of major amendment. (1) Submission of a major amendment to an original NDA, efficacy supplement, or resubmission of an NDA or efficacy supplement within 3 months of the end of the initial review cycle constitutes an agreement by the applicant under section 505(c) of the Federal Food, Drug, and Cosmetic Act to extend the initial review cycle by 3 months. (For references to a resubmission of an NDA or efficacy supplement in paragraph (b) of this section, the timeframe for reviewing the resubmission is the “review cycle” rather than the “initial review cycle.”) FDA may instead defer review of the amendment until the subsequent review cycle. If the agency extends the initial review cycle for an original NDA, efficacy supplement, or resubmission under this paragraph, the division responsible for reviewing the NDA, supplement, or resubmission will notify the applicant of the extension. The initial review cycle for an original NDA, efficacy supplement, or resubmission of an NDA or efficacy supplement may be extended only once due to submission of a major amendment. FDA may, at its discretion, review any subsequent major amendment during the initial review cycle (as extended) or defer review until the subsequent review cycle. (2) Submission of a major amendment to an original NDA, efficacy supplement, or resubmission of an NDA or efficacy supplement more than 3 months before the end of the initial review cycle will not extend the cycle. FDA may, at its discretion, review such an amendment during the initial review cycle or defer review until the subsequent review cycle. (3)… | |||
| 21:21:5.0.1.1.4.2.1.8 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.65 Withdrawal by the applicant of an unapproved application. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 68 FR 25287, May 12, 2003; 73 FR 39609, July 10, 2008] | An applicant may at any time withdraw an application that is not yet approved by notifying the Food and Drug Administration in writing. If, by the time it receives such notice, the agency has identified any deficiencies in the application, we will list such deficiencies in the letter we send the applicant acknowledging the withdrawal. A decision to withdraw the application is without prejudice to refiling. The agency will retain the application and will provide a copy to the applicant on request under the fee schedule in § 20.45 of FDA's public information regulations. | |||
| 21:21:5.0.1.1.4.2.1.9 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | B | Subpart B—Applications | § 314.70 Supplements and other changes to an approved NDA. | FDA | [69 FR 18764, Apr. 8, 2004, as amended at 71 FR 3997, Jan. 24, 2006; 72 FR 73600, Dec. 28, 2007; 73 FR 49609, Aug. 22, 2008; 81 FR 69648, Oct. 6, 2016] | (a) Changes to an approved NDA. (1)(i) Except as provided in paragraph (a)(1)(ii) of this section, the applicant must notify FDA about each change in each condition established in an approved NDA beyond the variations already provided for in the NDA. The notice is required to describe the change fully. Depending on the type of change, the applicant must notify FDA about the change in a supplement under paragraph (b) or (c) of this section or by inclusion of the information in the annual report to the NDA under paragraph (d) of this section. (ii) The submission and grant of a written request for an exception or alternative under § 201.26 of this chapter satisfies the applicable requirements in paragraphs (a) through (c) of this section. However, any grant of a request for an exception or alternative under § 201.26 of this chapter must be reported as part of the annual report to the NDA under paragraph (d) of this section. (2) The NDA holder must assess the effects of the change before distributing a drug product made with a manufacturing change. (3) Notwithstanding the requirements of paragraphs (b) and (c) of this section, an applicant must make a change provided for in those paragraphs in accordance with a regulation or guidance that provides for a less burdensome notification of the change (for example, by submission of a supplement that does not require approval prior to distribution of the product or in an annual report). (4) The applicant must promptly revise all promotional labeling and advertising to make it consistent with any labeling change implemented in accordance with paragraphs (b) and (c) of this section. (5) Except for a supplement providing for a change in the labeling, the applicant must include in each supplement and amendment to a supplement providing for a change under paragraph (b) or (c) of this section a statement certifying that a field copy has been provided in accordance with § 314.440(a)(4). (6) A supplement or annual report must include a list of all changes contained in the s… | |||
| 21:21:5.0.1.1.4.3.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.92 Drug products for which abbreviated applications may be submitted. | FDA | [57 FR 17983, Apr. 28, 1992, as amended at 64 FR 401, Jan. 5, 1999] | (a) Abbreviated applications are suitable for the following drug products within the limits set forth under § 314.93: (1) Drug products that are the same as a listed drug. A “listed drug” is defined in § 314.3. For determining the suitability of an abbreviated new drug application, the term “same as” means identical in active ingredient(s), dosage form, strength, route of administration, and conditions of use, except that conditions of use for which approval cannot be granted because of exclusivity or an existing patent may be omitted. If a listed drug has been voluntarily withdrawn from or not offered for sale by its manufacturer, a person who wishes to submit an abbreviated new drug application for the drug shall comply with § 314.122. (2) [Reserved] (3) Drug products that have been declared suitable for an abbreviated new drug application submission by FDA through the petition procedures set forth under § 10.30 of this chapter and § 314.93. (b) FDA will publish in the list listed drugs for which abbreviated applications may be submitted. The list is available from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402, 202-783-3238. | |||
| 21:21:5.0.1.1.4.3.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.93 Petition to request a change from a listed drug. | FDA | [57 FR 17983, Apr. 28, 1992, as amended at 81 FR 69649, Oct. 6, 2016] | (a) The only changes from a listed drug for which the agency will accept a petition under this section are those changes described in paragraph (b) of this section. Petitions to submit ANDAs for other changes from a listed drug will not be approved. (b) A person who wants to submit an ANDA for a drug product which is not identical to a listed drug in route of administration, dosage form, and strength, or in which one active ingredient is substituted for one of the active ingredients in a listed combination drug, must first obtain permission from FDA to submit such an ANDA. (c) To obtain permission to submit an ANDA for a change described in paragraph (b) of this section, a person must submit and obtain approval of a petition requesting the change. A person seeking permission to request such a change from a reference listed drug shall submit a petition in accordance with § 10.20 of this chapter and in the format specified in § 10.30 of this chapter. The petition shall contain the information specified in § 10.30 of this chapter and any additional information required by this section. If any provision of § 10.20 or § 10.30 of this chapter is inconsistent with any provision of this section, the provisions of this section apply. (d) The petitioner shall identify a listed drug and include a copy of the proposed labeling for the drug product that is the subject of the petition and a copy of the approved labeling for the listed drug. The petitioner may, under limited circumstances, identify more than one listed drug, for example, when the proposed drug product is a combination product that differs from the combination reference listed drug with regard to an active ingredient, and the different active ingredient is an active ingredient of a listed drug. The petitioner shall also include information to show that: (1) The active ingredients of the proposed drug product are of the same pharmacological or therapeutic class as those of the reference listed drug. (2) The drug product can be expected to have the same thera… | |||
| 21:21:5.0.1.1.4.3.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.94 Content and format of an ANDA. | FDA | [57 FR 17983, Apr. 28, 1992; 57 FR 29353, July 1, 1992, as amended at 58 FR 47352, Sept. 8, 1993; 59 FR 50364, Oct. 3, 1994; 63 FR 5252, Feb. 2, 1998; 63 FR 66399, Dec. 1, 1998; 64 FR 401, Jan. 5, 1999; 65 FR 56479, Sept. 19, 2000; 67 FR 77672, Dec. 19, 2002; 68 FR 69019, Dec. 11, 2003; 69 FR 18766, Apr. 8, 2004; 74 FR 2861, Jan. 16, 2009; 76 FR 13880, Mar. 15, 2011; 81 FR 69649, Oct. 6, 2016] | ANDAs are required to be submitted in the form and contain the information required under this section. Three copies of the ANDA are required, an archival copy, a review copy, and a field copy. FDA will maintain guidance documents on the format and content of ANDAs to assist applicants in their preparation. (a) ANDAs. Except as provided in paragraph (b) of this section, the applicant must submit a complete archival copy of the abbreviated new drug application that includes the following: (1) Application form. The applicant must submit a completed and signed application form that contains the information described under § 314.50(a)(1), (a)(3), (a)(4), and (a)(5). The applicant must state whether the submission is an ANDA under this section or a supplement to an ANDA under § 314.97. (2) Table of contents. The archival copy of the ANDA is required to contain a table of contents that shows the volume number and page number of the contents of the submission. (3) Basis for ANDA submission. An ANDA must refer to a listed drug. Ordinarily, that listed drug will be the drug product selected by the Agency as the reference standard for conducting bioequivalence testing. The ANDA must contain: (i) The name of the reference listed drug, including its dosage form and strength. For an ANDA based on an approved petition under § 10.30 of this chapter and § 314.93, the reference listed drug must be the same as the listed drug referenced in the approved petition. (ii) A statement as to whether, according to the information published in the list, the reference listed drug is entitled to a period of marketing exclusivity under section 505(j)(5)(F) of the Federal Food, Drug, and Cosmetic Act. (iii) For an ANDA based on an approved petition under § 10.30 of this chapter and § 314.93, a reference to the FDA-assigned docket number for the petition and a copy of FDA's correspondence approving the petition. (4) Conditions of use. (i) A statement that the conditions of use prescribed, recommended, or suggested in the labe… | |||
| 21:21:5.0.1.1.4.3.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.95 Notice of certification of invalidity, unenforceability, or noninfringement of a patent. | FDA | [81 FR 69651, Oct. 6, 2016, as amended at 84 FR 6673, Feb. 28, 2019] | (a) Notice of certification. For each patent that claims the listed drug or that claims a use for such listed drug for which the applicant is seeking approval and for which the applicant submits a paragraph IV certification, the applicant must send notice of such certification by registered or certified mail, return receipt requested, or by a designated delivery service, as defined in paragraph (g) of this section to each of the following persons: (1) Each owner of the patent that is the subject of the certification or the representative designated by the owner to receive the notice. The name and address of the patent owner or its representative may be obtained from the U.S. Patent and Trademark Office; and (2) The holder of the approved NDA under section 505(b) of the Federal Food, Drug, and Cosmetic Act for the listed drug that is claimed by the patent and for which the applicant is seeking approval, or, if the NDA holder does not reside or maintain a place of business within the United States, the NDA holder's attorney, agent, or other authorized official. The name and address of the NDA holder or its attorney, agent, or authorized official may be obtained by sending a written or electronic communication to the Central Document Room, Attn: Orange Book Staff, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266 or to the Orange Book Staff at the email address listed on the Agency's Web site at http://www.fda.gov . (3) This paragraph (a) does not apply to a method-of-use patent that does not claim a use for which the applicant is seeking approval. (4) An applicant may send notice by an alternative method only if FDA has agreed in advance that the method will produce an acceptable form of documentation. (b) Sending the notice. (1) Except as provided under paragraph (d) of this section, the applicant must send the notice required by paragraph (a) of this section on or after the date it receives a paragraph IV acknowledgment letter from FDA… | |||
| 21:21:5.0.1.1.4.3.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.96 Amendments to an unapproved ANDA. | FDA | [57 FR 17983, Apr. 28, 1992, as amended at 58 FR 47352, Sept. 8, 1993; 64 FR 401, Jan. 5, 1999; 73 FR 39609, July 10, 2008; 74 FR 2861, Jan. 16, 2009; 81 FR 69652, Oct. 6, 2016] | (a) ANDA. (1) An applicant may amend an ANDA that is submitted under § 314.94, but not yet approved, to revise existing information or provide additional information. Amendments containing bioequivalence studies must contain reports of all bioequivalence studies conducted by the applicant on the same drug product formulation, unless the information has previously been submitted to FDA in the ANDA. A complete study report must be submitted for any bioequivalence study upon which the applicant relies for approval. For all other bioequivalence studies conducted on the same drug product formulation as defined in § 314.3 of this chapter, the applicant must submit either a complete or summary report. If a summary report of a bioequivalence study is submitted and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may require that the applicant submit a complete report of the bioequivalence study to FDA. (2) Submission of an amendment containing significant data or information before the end of the initial review cycle constitutes an agreement between FDA and the applicant to extend the initial review cycle only for the time necessary to review the significant data or information and for no more than 180 days. (b) Field copy. The applicant must submit a field copy of each amendment under § 314.94(a)(9). The applicant, other than a foreign applicant, must include in its submission of each such amendment to FDA a statement certifying that a field copy of the amendment has been sent to the applicant's home FDA district office. (c) Different listed drug. An applicant may not amend an ANDA to seek approval of a drug referring to a listed drug that is different from the reference listed drug identified in the ANDA. This paragraph (c) applies if, at any time before the approval of the ANDA, a different listed drug is approved that is the pharmaceutical equivalent to the product in the ANDA and is designated as a reference listed drug. This paragraph (c) also applies if changes are … | |||
| 21:21:5.0.1.1.4.3.1.6 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.97 Supplements and other changes to an approved ANDA. | FDA | [81 FR 69653, Oct. 6, 2016] | (a) General requirements. The applicant must comply with the requirements of §§ 314.70 and 314.71 regarding the submission of supplemental ANDAs and other changes to an approved ANDA. (b) Different listed drug. An applicant may not supplement an ANDA to seek approval of a drug referring to a listed drug that is different from the current reference listed drug identified in the ANDA. This paragraph (b) applies if changes are proposed in a supplement to the ANDA such that the proposed product is a pharmaceutical equivalent to a different listed drug than the reference listed drug identified in the ANDA. A change of reference listed drug must be submitted in a new ANDA. However, notwithstanding the limitation described in this paragraph (b), an applicant may supplement the ANDA to seek approval of a different strength. | |||
| 21:21:5.0.1.1.4.3.1.7 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.98 Postmarketing reports. | FDA | [79 FR 33089, June 10, 2014] | (a) Each applicant having an approved abbreviated new drug application under § 314.94 that is effective must comply with the requirements of § 314.80 regarding the reporting and recordkeeping of adverse drug experiences. (b) Each applicant must make the reports required under § 314.81 and section 505(k) of the Federal Food, Drug, and Cosmetic Act for each of its approved abbreviated applications. | |||
| 21:21:5.0.1.1.4.3.1.8 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | C | Subpart C—Abbreviated Applications | § 314.99 Other responsibilities of an applicant of an ANDA. | FDA | 81 FR 69653, Oct. 6, 2016] | (a) An applicant must comply with the requirements of § 314.65 regarding withdrawal by the applicant of an unapproved ANDA and § 314.72 regarding a change in ownership of an ANDA. (b) An applicant may ask FDA to waive under this section any requirement that applies to the applicant under §§ 314.92 through 314.99. The applicant must comply with the requirements for a waiver under § 314.90. If FDA grants the applicant's waiver request with respect to a requirement under §§ 314.92 through 314.99, the waived requirement will not constitute a basis for refusal to approve an ANDA under § 314.127. | |||
| 21:21:5.0.1.1.4.4.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.100 Timeframes for reviewing applications and abbreviated applications. | FDA | [73 FR 39609, July 10, 2008] | (a) Except as provided in paragraph (c) of this section, within 180 days of receipt of an application for a new drug under section 505(b) of the act or an abbreviated application for a new drug under section 505(j) of the act, FDA will review it and send the applicant either an approval letter under § 314.105 or a complete response letter under § 314.110. This 180-day period is called the “initial review cycle.” (b) At any time before approval, an applicant may withdraw an application under § 314.65 or an abbreviated application under § 314.99 and later submit it again for consideration. (c) The initial review cycle may be adjusted by mutual agreement between FDA and an applicant or as provided in §§ 314.60 and 314.96, as the result of a major amendment. | |||
| 21:21:5.0.1.1.4.4.1.10 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.110 Complete response letter to the applicant. | FDA | [73 FR 39609, July 10, 2008] | (a) Complete response letter. FDA will send the applicant a complete response letter if the agency determines that we will not approve the application or abbreviated application in its present form for one or more of the reasons given in § 314.125 or § 314.127, respectively. (1) Description of specific deficiencies. A complete response letter will describe all of the specific deficiencies that the agency has identified in an application or abbreviated application, except as stated in paragraph (a)(3) of this section. (2) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in an original application or abbreviated application (or, where appropriate, a resubmission) and any amendments that the agency has reviewed. The complete response letter will identify any amendments that the agency has not yet reviewed. (3) Inadequate data. If FDA determines, after an application is filed or an abbreviated application is received, that the data submitted are inadequate to support approval, the agency might issue a complete response letter without first conducting required inspections and/or reviewing proposed product labeling. (4) Recommendation of actions for approval. When possible, a complete response letter will recommend actions that the applicant might take to place the application or abbreviated application in condition for approval. (b) Applicant actions. After receiving a complete response letter, the applicant must take one of following actions: (1) Resubmission. Resubmit the application or abbreviated application, addressing all deficiencies identified in the complete response letter. (i) A resubmission of an application or efficacy supplement that FDA classifies as a Class 1 resubmission constitutes an agreement by the applicant to start a new 2-month review cycle beginning on the date FDA receives the resubmission. (ii) A resubmission of an application or efficacy supplement that FDA classifies as a Class 2 resubmission constitutes an agree… | |||
| 21:21:5.0.1.1.4.4.1.11 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.120 [Reserved] | FDA | |||||
| 21:21:5.0.1.1.4.4.1.12 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.122 Submitting an abbreviated application for, or a 505(j)(2)(C) petition that relies on, a listed drug that is no longer marketed. | FDA | [57 FR 17990, Apr. 28, 1992; 57 FR 29353, July 1, 1992] | (a) An abbreviated new drug application that refers to, or a petition under section 505(j)(2)(C) of the act and § 314.93 that relies on, a listed drug that has been voluntarily withdrawn from sale in the United States must be accompanied by a petition seeking a determination whether the listed drug was withdrawn for safety or effectiveness reasons. The petition must be submitted under §§ 10.25(a) and 10.30 of this chapter and must contain all evidence available to the petitioner concerning the reasons for the withdrawal from sale. (b) When a petition described in paragraph (a) of this section is submitted, the agency will consider the evidence in the petition and any other evidence before the agency, and determine whether the listed drug is withdrawn from sale for safety or effectiveness reasons, in accordance with the procedures in § 314.161. (c) An abbreviated new drug application described in paragraph (a) of this section will be disapproved, under § 314.127(a)(11), and a 505(j)(2)(C) petition described in paragraph (a) of this section will be disapproved, under § 314.93(e)(1)(iv), unless the agency determines that the withdrawal of the listed drug was not for safety or effectiveness reasons. (d) Certain drug products approved for safety and effectiveness that were no longer marketed on September 24, 1984, are not included in the list. Any person who wishes to obtain marketing approval for such a drug product under an abbreviated new drug application must petition FDA for a determination whether the drug product was withdrawn from the market for safety or effectiveness reasons and request that the list be amended to include the drug product. A person seeking such a determination shall use the petition procedures established in § 10.30 of this chapter. The petitioner shall include in the petition information to show that the drug product was approved for safety and effectiveness and all evidence available to the petitioner concerning the reason that marketing of the drug product ceased. | |||
| 21:21:5.0.1.1.4.4.1.13 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.125 Refusal to approve an NDA. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 53 FR 41524, Oct. 21, 1988; 57 FR 17991, Apr. 28, 1992; 58 FR 25926, Apr. 28, 1993; 64 FR 402, Jan. 5, 1999; 73 FR 39610, July 10, 2008; 74 FR 9766, Mar. 6, 2009; 81 FR 60221, Aug. 31, 2016; 81 FR 69658, Oct. 6, 2016; 89 FR 105331, Dec. 26, 2024] | (a) The Food and Drug Administration will refuse to approve the NDA and for a new drug give the applicant written notice of an opportunity for a hearing under § 314.200 on the question of whether there are grounds for denying approval of the NDA under section 505(d) of the Federal Food, Drug, and Cosmetic Act, if: (1) FDA sends the applicant a complete response letter under § 314.110; (2) The applicant requests an opportunity for hearing for a new drug on the question of whether the NDA is approvable; and (3) FDA finds that any of the reasons given in paragraph (b) of this section apply. (b) FDA may refuse to approve an NDA for any of the following reasons, unless the requirement has been waived under § 314.90: (1) The methods to be used in, and the facilities and controls used for, the manufacture, processing, packing, or holding of the drug substance or the drug product are inadequate to preserve its identity, strength, quality, purity, stability, and bioavailability. (2) The investigations required under section 505(b) of the Federal Food, Drug, and Cosmetic Act do not include adequate tests by all methods reasonably applicable to show whether or not the drug is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling. (3) The results of the tests show that the drug is unsafe for use under the conditions prescribed, recommended, or suggested in its proposed labeling or the results do not show that the drug product is safe for use under those conditions. (4) There is insufficient information about the drug to determine whether the product is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling. (5) There is a lack of substantial evidence consisting of adequate and well-controlled investigations, as defined in § 314.126, that the drug product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling. (6) The proposed labeling is … | |||
| 21:21:5.0.1.1.4.4.1.14 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.126 Adequate and well-controlled studies. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 55 FR 11580, Mar. 29, 1990; 64 FR 402, Jan. 5, 1999; 67 FR 9586, Mar. 4, 2002] | (a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been developed over a period of years and are recognized by the scientific community as the essentials of an adequate and well-controlled clinical investigation. The Food and Drug Administration considers these characteristics in determining whether an investigation is adequate and well-controlled for purposes of section 505 of the act. Reports of adequate and well-controlled investigations provide the primary basis for determining whether there is “substantial evidence” to support the claims of effectiveness for new drugs. Therefore, the study report should provide sufficient details of study design, conduct, and analysis to allow critical evaluation and a determination of whether the characteristics of an adequate and well-controlled study are present. (b) An adequate and well-controlled study has the following characteristics: (1) There is a clear statement of the objectives of the investigation and a summary of the proposed or actual methods of analysis in the protocol for the study and in the report of its results. In addition, the protocol should contain a description of the proposed methods of analysis, and the study report should contain a description of the methods of analysis ultimately used. If the protocol does not contain a description of the proposed methods of analysis, the study report should describe how the methods used were selected. (2) The study uses a design that permits a valid comparison with a control to provide a quantitative assessment of drug effect. The protocol for the study and report of results should describe the study design precisely; for example, duration of treatment periods, whether treatments are parallel, sequential, or crossover, and whether the sample size is predetermined or based up… | |||
| 21:21:5.0.1.1.4.4.1.15 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.127 Refusal to approve an ANDA. | FDA | [57 FR 17991, Apr. 28, 1992; 57 FR 29353, July 1, 1992, as amended at 58 FR 25927, Apr. 28, 1993; 67 FR 77672, Dec. 19, 2002; 81 FR 69658, Oct. 6, 2016; 89 FR 105331, Dec. 26, 2024] | (a) FDA will refuse to approve an ANDA for a new drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act for any of the following reasons, unless the requirement has been waived under § 314.99: (1) The methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the drug product are inadequate to ensure and preserve its identity, strength, quality, and purity. (2) Information submitted with the ANDA is insufficient to show that each of the proposed conditions of use has been previously approved for the listed drug referred to in the ANDA. (3)(i) If the reference listed drug has only one active ingredient, information submitted with the ANDA is insufficient to show that the active ingredient is the same as that of the reference listed drug; (ii) If the reference listed drug has more than one active ingredient, information submitted with the ANDA is insufficient to show that the active ingredients are the same as the active ingredients of the reference listed drug; or (iii) If the reference listed drug has more than one active ingredient and if the ANDAis for a drug product that has an active ingredient different from the reference listed drug: (A) Information submitted with the ANDA is insufficient to show: ( 1 ) That the other active ingredients are the same as the active ingredients of the reference listed drug; or ( 2 ) That the different active ingredient is an active ingredient of a listed drug or a drug that does not meet the requirements of section 201(p) of the Federal Food, Drug, and Cosmetic Act; or (B) No petition to submit an ANDA for the drug product with the different active ingredient was approved under § 314.93. (4)(i) If the ANDA is for a drug product whose route of administration, dosage form, or strength purports to be the same as that of the listed drug referred to in the ANDA, information submitted in the abbreviated new drug application is insufficient to show that the route of administration, dosage form, or strength is the sam… | |||
| 21:21:5.0.1.1.4.4.1.16 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.150 Withdrawal of approval of an application or abbreviated application. | FDA | [57 FR 17993, Apr. 28, 1992, as amended at 58 FR 25927, Apr. 28, 1993; 64 FR 402, Jan. 5, 1999] | (a) The Food and Drug Administration will notify the applicant, and, if appropriate, all other persons who manufacture or distribute identical, related, or similar drug products as defined in §§ 310.6 and 314.151(a) of this chapter and for a new drug afford an opportunity for a hearing on a proposal to withdraw approval of the application or abbreviated new drug application under section 505(e) of the act and under the procedure in § 314.200, if any of the following apply: (1) The Secretary of Health and Human Services has suspended the approval of the application or abbreviated application for a new drug on a finding that there is an imminent hazard to the public health. FDA will promptly afford the applicant an expedited hearing following summary suspension on a finding of imminent hazard to health. (2) FDA finds: (i) That clinical or other experience, tests, or other scientific data show that the drug is unsafe for use under the conditions of use upon the basis of which the application or abbreviated application was approved; or (ii) That new evidence of clinical experience, not contained in the application or not available to FDA until after the application or abbreviated application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when the application or abbreviated application was approved, evaluated together with the evidence available when the application or abbreviated application was approved, reveal that the drug is not shown to be safe for use under the conditions of use upon the basis of which the application or abbreviated application was approved; or (iii) Upon the basis of new information before FDA with respect to the drug, evaluated together with the evidence available when the application or abbreviated application was approved, that there is a lack of substantial evidence from adequate and well-controlled investigations as defined in § 314.126, that the drug will have the effect it is purported or represented to have under the conditions of use p… | |||
| 21:21:5.0.1.1.4.4.1.17 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.151 Withdrawal of approval of an abbreviated new drug application under section 505(j)(5) of the act. | FDA | [57 FR 17994, Apr. 28, 1992, as amended at 88 FR 45066, July 14, 2023] | (a) Approval of an abbreviated new drug application approved under § 314.105(d) may be withdrawn when the agency withdraws approval, under § 314.150(a) or under this section, of the approved drug referred to in the abbreviated new drug application. If the agency proposed to withdraw approval of a listed drug under § 314.150(a), the holder of an approved application for the listed drug has a right to notice and opportunity for hearing. The published notice of opportunity for hearing will identify all drug products approved under § 314.105(d) whose applications are subject to withdrawal under this section if the listed drug is withdrawn, and will propose to withdraw such drugs. Holders of approved applications for the identified drug products will be provided notice and an opportunity to respond to the proposed withdrawal of their applications as described in paragraphs (b) and (c) of this section. (b)(1) The published notice of opportunity for hearing on the withdrawal of the listed drug will serve as notice to holders of identified abbreviated new drug applications of the grounds for the proposed withdrawal. (2) Holders of applications for drug products identified in the notice of opportunity for hearing may submit written comments on the notice of opportunity for hearing issued on the proposed withdrawal of the listed drug. If an abbreviated new drug application holder submits comments on the notice of opportunity for hearing and a hearing is granted, the abbreviated new drug application holder may participate in the hearing as a nonparty participant as provided for in § 12.89 of this chapter. (3) Except as provided in paragraphs (c) and (d) of this section, the approval of an abbreviated new drug application for a drug product identified in the notice of opportunity for hearing on the withdrawal of a listed drug will be withdrawn when the agency has completed the withdrawal of approval of the listed drug. (c)(1) If the holder of an application for a drug identified in the notice of opportunity for hearing h… | |||
| 21:21:5.0.1.1.4.4.1.18 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.152 Notice of withdrawal of approval of an application or abbreviated application for a new drug. | FDA | [57 FR 17994, Apr. 28, 1992] | If the Food and Drug Administration withdraws approval of an application or abbreviated application for a new drug, FDA will publish a notice in the Federal Register announcing the withdrawal of approval. If the application or abbreviated application was withdrawn for grounds described in § 314.150(a) or § 314.151, the notice will announce the removal of the drug from the list of approved drugs published under section 505(j)(6) of the act and shall satisfy the requirement of § 314.162(b). | |||
| 21:21:5.0.1.1.4.4.1.19 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.153 Suspension of approval of an abbreviated new drug application. | FDA | [57 FR 17995, Apr. 28, 1992, as amended at 88 FR 45066, July 14, 2023] | (a) Suspension of approval. The approval of an abbreviated new drug application approved under § 314.105(d) shall be suspended for the period stated when: (1) The Secretary of the Department of Health and Human Services, under the imminent hazard authority of section 505(e) of the act or the authority of this paragraph, suspends approval of a listed drug referred to in the abbreviated new drug application, for the period of the suspension; (2) The agency, in the notice described in paragraph (b) of this section, or in any subsequent written notice given an abbreviated new drug application holder by the agency, concludes that the risk of continued marketing and use of the drug is inappropriate, pending completion of proceedings to withdraw or suspend approval under § 314.151 or paragraph (b) of this section; or (3) The agency, under the procedures set forth in paragraph (b) of this section, issues a final decision stating the determination that the abbreviated application is suspended because the listed drug on which the approval of the abbreviated new drug application depends has been withdrawn from sale for reasons of safety or effectiveness or has been suspended under paragraph (b) of this section. The suspension will take effect on the date stated in the decision and will remain in effect until the agency determines that the marketing of the drug has resumed or that the withdrawal is not for safety or effectiveness reasons. (b) Procedures for suspension of abbreviated new drug applications when a listed drug is voluntarily withdrawn for safety or effectiveness reasons. (1) If a listed drug is voluntarily withdrawn from sale, and the agency determines that the withdrawal from sale was for reasons of safety or effectiveness, the agency will send each holder of an approved abbreviated new drug application that is subject to suspension as a result of this determination a copy of the agency's initial decision setting forth the reasons for the determination. The initial decision will also be placed on file w… | |||
| 21:21:5.0.1.1.4.4.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.101 Filing an NDA and receiving an ANDA. | FDA | [81 FR 69653, Oct. 6, 2016] | (a) Filing an NDA. (1) Within 60 days after FDA receives an NDA, the Agency will determine whether the NDA may be filed. The filing of an NDA means that FDA has made a threshold determination that the NDA is sufficiently complete to permit a substantive review. (2) If FDA finds that none of the reasons in paragraphs (d) and (e) of this section for refusing to file the NDA apply, the Agency will file the NDA and notify the applicant in writing. In the case of a 505(b)(2) application that contains a paragraph IV certification, the applicant will be notified via a paragraph IV acknowledgment letter. The date of filing will be the date 60 days after the date FDA received the NDA. The date of filing begins the 180-day period described in section 505(c) of the Federal Food, Drug, and Cosmetic Act. This 180-day period is called the “filing clock.” (3) If FDA refuses to file the NDA, the Agency will notify the applicant in writing and state the reason under paragraph (d) or (e) of this section for the refusal. If FDA refuses to file the NDA under paragraph (d) of this section, the applicant may request in writing within 30 days of the date of the Agency's notification an informal conference with the Agency about whether the Agency should file the NDA. If, following the informal conference, the applicant requests that FDA file the NDA (with or without amendments to correct the deficiencies), the Agency will file the NDA over protest under paragraph (a)(2) of this section, notify the applicant in writing, and review it as filed. If the NDA is filed over protest, the date of filing will be the date 60 days after the date the applicant requested the informal conference. The applicant need not resubmit a copy of an NDA that is filed over protest. If FDA refuses to file the NDA under paragraph (e) of this section, the applicant may amend the NDA and resubmit it, and the Agency will make a determination under this section whether it may be filed. (b)(1) Receiving an ANDA. An ANDA will be evaluated after it is submitted t… | |||
| 21:21:5.0.1.1.4.4.1.20 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.160 Approval of an application or abbreviated application for which approval was previously refused, suspended, or withdrawn. | FDA | [57 FR 17995, Apr. 28, 1992] | Upon the Food and Drug Administration's own initiative or upon request of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the Federal Register announcing the approval. | |||
| 21:21:5.0.1.1.4.4.1.21 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.161 Determination of reasons for voluntary withdrawal of a listed drug. | FDA | [57 FR 17995, Apr. 28, 1992] | (a) A determination whether a listed drug that has been voluntarily withdrawn from sale was withdrawn for safety or effectiveness reasons may be made by the agency at any time after the drug has been voluntarily withdrawn from sale, but must be made: (1) Prior to approving an abbreviated new drug application that refers to the listed drug; (2) Whenever a listed drug is voluntarily withdrawn from sale and abbreviated new drug applications that referred to the listed drug have been approved; and (3) When a person petitions for such a determination under §§ 10.25(a) and 10.30 of this chapter. (b) Any person may petition under §§ 10.25(a) and 10.30 of this chapter for a determination whether a listed drug has been voluntarily withdrawn for safety or effectiveness reasons. Any such petition must contain all evidence available to the petitioner concerning the reason that the drug is withdrawn from sale. (c) If the agency determines that a listed drug is withdrawn from sale for safety or effectiveness reasons, the agency will, except as provided in paragraph (d) of this section, publish a notice of the determination in the Federal Register. (d) If the agency determines under paragraph (a) of this section that a listed drug is withdrawn from sale for safety and effectiveness reasons and there are approved abbreviated new drug applications that are subject to suspension under section 505(j)(5) of the act, FDA will initiate a proceeding in accordance with § 314.153(b). (e) A drug that the agency determines is withdrawn for safety or effectiveness reasons will be removed from the list, under § 314.162. The drug may be relisted if the agency has evidence that marketing of the drug has resumed or that the withdrawal is not for safety or effectiveness reasons. A determination that the drug is not withdrawn for safety or effectiveness reasons may be made at any time after its removal from the list, upon the agency's initiative, or upon the submission of a petition under §§ 10.25(a) and 10.30 of this chapter. If the agen… | |||
| 21:21:5.0.1.1.4.4.1.22 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.162 Removal of a drug product from the list. | FDA | [57 FR 17996, Apr. 28, 1992] | (a) FDA will remove a previously approved new drug product from the list for the period stated when: (1) The agency withdraws or suspends approval of a new drug application or an abbreviated new drug application under § 314.150(a) or § 314.151 or under the imminent hazard authority of section 505(e) of the act, for the same period as the withdrawal or suspension of the application; or (2) The agency, in accordance with the procedures in § 314.153(b) or § 314.161, issues a final decision stating that the listed drug was withdrawn from sale for safety or effectiveness reasons, or suspended under § 314.153(b), until the agency determines that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA will publish in the Federal Register a notice announcing the removal of a drug from the list. (c) At the end of the period specified in paragraph (a)(1) or (a)(2) of this section, FDA will relist a drug that has been removed from the list. The agency will publish in the Federal Register a notice announcing the relisting of the drug. | |||
| 21:21:5.0.1.1.4.4.1.23 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.170 Adulteration and misbranding of an approved drug. | FDA | [50 FR 7493, Feb. 22, 1985. Redesignated at 57 FR 17983, Apr. 28, 1992, and amended at 64 FR 402, Jan. 5, 1999] | All drugs, including those the Food and Drug Administration approves under section 505 of the act and this part, are subject to the adulteration and misbranding provisions in sections 501, 502, and 503 of the act. FDA is authorized to regulate approved new drugs by regulations issued through informal rulemaking under sections 501, 502, and 503 of the act. | |||
| 21:21:5.0.1.1.4.4.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.102 Communications between FDA and applicants. | FDA | [57 FR 17988, Apr. 28, 1992; 57 FR 29353, July 1, 1992, as amended at 73 FR 39609, July 10, 2008] | (a) General principles. During the course of reviewing an application or an abbreviated application, FDA shall communicate with applicants about scientific, medical, and procedural issues that arise during the review process. Such communication may take the form of telephone conversations, letters, or meetings, whichever is most appropriate to discuss the particular issue at hand. Communications shall be appropriately documented in the application in accordance with § 10.65 of this chapter. Further details on the procedures for communication between FDA and applicants are contained in a staff manual guide that is publicly available. (b) Notification of easily correctable deficiencies. FDA reviewers shall make every reasonable effort to communicate promptly to applicants easily correctable deficiencies found in an application or an abbreviated application when those deficiencies are discovered, particularly deficiencies concerning chemistry, manufacturing, and controls issues. The agency will also inform applicants promptly of its need for more data or information or for technical changes in the application or the abbreviated application needed to facilitate the agency's review. This early communication is intended to permit applicants to correct such readily identified deficiencies relatively early in the review process and to submit an amendment before the review period has elapsed. Such early communication would not ordinarily apply to major scientific issues, which require consideration of the entire pending application or abbreviated application by agency managers as well as reviewing staff. Instead, major scientific issues will ordinarily be addressed in a complete response letter. (c) Ninety-day conference. Approximately 90 days after the agency receives the application, FDA will provide applicants with an opportunity to meet with agency reviewing officials. The purpose of the meeting will be to inform applicants of the general progress and status of their applications, and to advise applicants of d… | |||
| 21:21:5.0.1.1.4.4.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.103 Dispute resolution. | FDA | [50 FR 7493, Feb. 22, 1985; 50 FR 14212, Apr. 11, 1985, as amended at 57 FR 17989, Apr. 28, 1992; 73 FR 39609, July 10, 2008] | (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated applications as quickly and amicably as possible through the cooperative exchange of information and views. (b) Administrative and procedural issues. When administrative or procedural disputes arise, the applicant should first attempt to resolve the matter with the division responsible for reviewing the application or abbreviated application, beginning with the consumer safety officer assigned to the application or abbreviated application. If resolution is not achieved, the applicant may raise the matter with the person designated as ombudsman, whose function shall be to investigate what has happened and to facilitate a timely and equitable resolution. Appropriate issues to raise with the ombudsman include resolving difficulties in scheduling meetings, obtaining timely replies to inquiries, and obtaining timely completion of pending reviews. Further details on this procedure are contained in a staff manual guide that is publicly available under FDA's public information regulations in part 20. (c) Scientific and medical disputes. (1) Because major scientific issues are ordinarily communicated to applicants in a complete response letter pursuant to § 314.110, the “end-of-review conference” described in § 314.102(d) will provide a timely forum for discussing and resolving, if possible, scientific and medical issues on which the applicant disagrees with the agency. In addition, the “ninety-day conference” described in § 314.102(c) will provide a timely forum for discussing and resolving, if possible, issues identified by that date. (2) When scientific or medical disputes arise at other times during the review process, applicants should discuss the matter directly with the responsible reviewing officials. If necessary, applicants may request a meeting with the appropriate reviewing officials and management representatives in order to seek … | |||
| 21:21:5.0.1.1.4.4.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.104 Drugs with potential for abuse. | FDA | [57 FR 17989, Apr. 28, 1992] | The Food and Drug Administration will inform the Drug Enforcement Administration under section 201(f) of the Controlled Substances Act (21 U.S.C. 801) when an application or abbreviated application is submitted for a drug that appears to have an abuse potential. | |||
| 21:21:5.0.1.1.4.4.1.6 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.105 Approval of an NDA and an ANDA. | FDA | [81 FR 69654, Oct. 6, 2016] | (a) FDA will approve an NDA and send the applicant an approval letter if none of the reasons in § 314.125 for refusing to approve the NDA applies. FDA will issue a tentative approval letter if an NDA otherwise meets the requirements for approval under the Federal Food, Drug, and Cosmetic Act, but cannot be approved because there is a 7-year period of orphan exclusivity for the listed drug under section 527 of the Federal Food, Drug, and Cosmetic Act and § 316.31 of this chapter, or if a 505(b)(2) application otherwise meets the requirements for approval under the Federal Food, Drug, and Cosmetic Act, but cannot be approved until the conditions in § 314.107(b)(3) are met; because there is a period of exclusivity for the listed drug under § 314.108; because there is a period of pediatric exclusivity for the listed drug under section 505A of the Federal Food, Drug, and Cosmetic Act; or because there is a period of exclusivity for the listed drug under section 505E of the Federal Food, Drug, and Cosmetic Act. A drug product that is granted tentative approval is not an approved drug and will not be approved until FDA issues an approval after any necessary additional review of the NDA. FDA's tentative approval of a drug product is based on information available to FDA at the time of the tentative approval letter ( i.e., information in the 505(b)(2) application and the status of current good manufacturing practices of the facilities used in the manufacturing and testing of the drug product) and is therefore subject to change on the basis of new information that may come to FDA's attention. A new drug product may not be marketed until the date of approval. (b) FDA will approve an NDA and issue the applicant an approval letter on the basis of draft labeling if the only deficiencies in the NDA concern editorial or similar minor deficiencies in the draft labeling. Such approval will be conditioned upon the applicant incorporating the specified labeling changes exactly as directed, and upon the applicant submitting to FDA … | |||
| 21:21:5.0.1.1.4.4.1.7 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.106 Foreign data. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 55 FR 11580, Mar. 29, 1990] | (a) General. The acceptance of foreign data in an application generally is governed by § 312.120 of this chapter. (b) As sole basis for marketing approval. An application based solely on foreign clinical data meeting U.S. criteria for marketing approval may be approved if: (1) The foreign data are applicable to the U.S. population and U.S. medical practice; (2) the studies have been performed by clinical investigators of recognized competence; and (3) the data may be considered valid without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of an application to meet any of these criteria will result in the application not being approvable based on the foreign data alone. FDA will apply this policy in a flexible manner according to the nature of the drug and the data being considered. (c) Consultation between FDA and applicants. Applicants are encouraged to meet with agency officials in a “presubmission” meeting when approval based solely on foreign data will be sought. | |||
| 21:21:5.0.1.1.4.4.1.8 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.107 Date of approval of a 505(b)(2) application or ANDA. | FDA | [81 FR 69655, Oct. 6, 2016] | (a) General. A drug product may be introduced or delivered for introduction into interstate commerce when the 505(b)(2) application or ANDA for the drug product is approved. A 505(b)(2) application or ANDA for a drug product is approved on the date FDA issues an approval letter under § 314.105 for the 505(b)(2) application or ANDA. (b) Effect of patent(s) on the listed drug. As described in paragraphs (b)(1) and (2) of this section, the status of patents listed for the listed drug(s) relied upon or reference listed drug, as applicable, must be considered in determining the first possible date on which a 505(b)(2) application or ANDA can be approved. The criteria in paragraphs (b)(1) and (2) of this section will be used to determine, for each relevant patent, the date that patent will no longer prevent approval. The first possible date on which the 505(b)(2) application or ANDA can be approved will be calculated for each patent, and the 505(b)(2) application or ANDA may be approved on the last applicable date. (1) Timing of approval based on patent certification or statement. If none of the reasons in § 314.125 or § 314.127, as applicable, for refusing to approve the 505(b)(2) application or ANDA applies, and none of the reasons in paragraph (d) of this section for delaying approval applies, the 505(b)(2) application or ANDA may be approved as follows: (i) Immediately, if the applicant certifies under § 314.50(i) or § 314.94(a)(12) that: (A) The applicant is aware of a relevant patent but the patent information required under section 505(b) or (c) of the Federal Food, Drug, and Cosmetic Act has not been submitted to FDA; or (B) The relevant patent has expired; or (C) The relevant patent is invalid, unenforceable, or will not be infringed, except as provided in paragraphs (b)(3) and (c) of this section, and the 45-day period provided for in section 505(c)(3)(C) and (j)(5)(B)(iii) of the Federal Food, Drug, and Cosmetic Act has expired; or (D) There are no relevant patents. (ii) Immediately, if the app… | |||
| 21:21:5.0.1.1.4.4.1.9 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | D | Subpart D—FDA Action on Applications and Abbreviated Applications | § 314.108 New drug product exclusivity. | FDA | [59 FR 50368, Oct. 3, 1994, as amended at 81 FR 69657, Oct. 6, 2016] | (a) Definitions. The definitions in § 314.3 and the following definitions of terms apply to this section: Approved under section 505(b) means an NDA submitted under section 505(b) and approved on or after October 10, 1962, or an application that was “deemed approved” under section 107(c)(2) of Public Law 87-781. Bioavailability study means a study to determine the bioavailability or the pharmacokinetics of a drug. Clinical investigation means any experiment other than a bioavailability study in which a drug is administered or dispensed to, or used on, human subjects. Conducted or sponsored by the applicant with regard to an investigation means that before or during the investigation, the applicant was named in Form FDA-1571 filed with FDA as the sponsor of the investigational new drug application under which the investigation was conducted, or the applicant or the applicant's predecessor in interest, provided substantial support for the investigation. To demonstrate “substantial support,” an applicant must either provide a certified statement from a certified public accountant that the applicant provided 50 percent or more of the cost of conducting the study or provide an explanation why FDA should consider the applicant to have conducted or sponsored the study if the applicant's financial contribution to the study is less than 50 percent or the applicant did not sponsor the investigational new drug. A predecessor in interest is an entity, e.g., a corporation, that the applicant has taken over, merged with, or purchased, or from which the applicant has purchased all rights to the drug. Purchase of nonexclusive rights to a clinical investigation after it is completed is not sufficient to satisfy this definition. Essential to approval means, with regard to an investigation, that there are no other data available that could support approval of the NDA. New chemical entity means a drug that contains no active moiety that has been approved by FDA in any other NDA submitted under section 505(b) of the Fed… | |||
| 21:21:5.0.1.1.4.5.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | E | Subpart E—Hearing Procedures for New Drugs | § 314.200 Notice of opportunity for hearing; notice of participation and request for hearing; grant or denial of hearing. | FDA | [50 FR 7493, Feb. 22, 1985; 50 FR 14212, Apr. 11, 1985, as amended at 50 FR 21238, May 23, 1985; 55 FR 11580, Mar. 29, 1990; 57 FR 17996, Apr. 28, 1992; 59 FR 14364, Mar. 28, 1994; 63 FR 5252, Feb. 2, 1998; 67 FR 9586, Mar. 4, 2002; 68 FR 24879, May 9, 2003; 69 FR 48775, Aug. 11, 2004; 74 FR 13113, Mar. 26, 2009; 88 FR 45066, July 14, 2023] | (a) Notice of opportunity for hearing. The Director of the Center for Drug Evaluation and Research, Food and Drug Administration, will give the applicant, and all other persons who manufacture or distribute identical, related, or similar drug products as defined in § 310.6 of this chapter, notice and an opportunity for a hearing on the Center's proposal to refuse to approve an application or to withdraw the approval of an application or abbreviated application under section 505(e) of the act. The notice will state the reasons for the action and the proposed grounds for the order. (1) The notice may be general (that is, simply summarizing in a general way the information resulting in the notice) or specific (that is, either referring to specific requirements in the statute and regulations with which there is a lack of compliance, or providing a detailed description and analysis of the specific facts resulting in the notice). (2) FDA will publish the notice in the Federal Register and will state that the applicant, and other persons subject to the notice under § 310.6, who wishes to participate in a hearing, has 30 days after the date of publication of the notice to file a written notice of participation and request for hearing. The applicant, or other persons subject to the notice under § 310.6, who fails to file a written notice of participation and request for hearing within 30 days, waives the opportunity for a hearing. (3) It is the responsibility of every manufacturer and distributor of a drug product to review every notice of opportunity for a hearing published in the Federal Register to determine whether it covers any drug product that person manufactures or distributes. Any person may request an opinion of the applicability of a notice to a specific product that may be identical, related, or similar to a product listed in a notice by writing to the Division of New Drugs and Labeling Compliance, Office of Compliance, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New H… | |||
| 21:21:5.0.1.1.4.5.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | E | Subpart E—Hearing Procedures for New Drugs | § 314.201 Procedure for hearings. | FDA | Parts 10 through 16 apply to hearings relating to new drugs under section 505 (d) and (e) of the act. | ||||
| 21:21:5.0.1.1.4.5.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | E | Subpart E—Hearing Procedures for New Drugs | § 314.235 Judicial review. | FDA | (a) The Commissioner of Food and Drugs will certify the transcript and record. In any case in which the Commissioner enters an order without a hearing under § 314.200(g), the record certified by the Commissioner is required to include the requests for hearing together with the data and information submitted and the Commissioner's findings and conclusion. (b) A manufacturer or distributor of an identical, related, or similar drug product under § 310.6 may seek judicial review of an order withdrawing approval of a new drug application, whether or not a hearing has been held, in a United States court of appeals under section 505(h) of the act. | ||||
| 21:21:5.0.1.1.4.7.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | G | Subpart G—Miscellaneous Provisions | § 314.410 Imports and exports of new drugs. | FDA | [50 FR 7493, Feb. 22, 1985. Redesignated at 57 FR 17983, Apr. 28, 1992, and amended at 64 FR 402, Jan. 5, 1999; 69 FR 18766, Apr. 8, 2004] | (a) Imports. (1) A new drug may be imported into the United States if: (i) It is the subject of an approved application under this part; or (ii) it complies with the regulations pertaining to investigational new drugs under part 312; and it complies with the general regulations pertaining to imports under subpart E of part 1. (2) A drug substance intended for use in the manufacture, processing, or repacking of a new drug may be imported into the United States if it complies with the labeling exemption in § 201.122 pertaining to shipments of drug substances in domestic commerce. (b) Exports. (1) A new drug may be exported if it is the subject of an approved application under this part or it complies with the regulations pertaining to investigational new drugs under part 312. (2) A new drug substance that is covered by an application approved under this part for use in the manufacture of an approved drug product may be exported by the applicant or any person listed as a supplier in the approved application, provided the drug substance intended for export meets the specification of, and is shipped with a copy of the labeling required for, the approved drug product. (3) Insulin or an antibiotic drug may be exported without regard to the requirements in section 802 of the act if the insulin or antibiotic drug meets the requirements of section 801(e)(1) of the act. | |||
| 21:21:5.0.1.1.4.7.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | G | Subpart G—Miscellaneous Provisions | § 314.420 Drug master files. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 53 FR 33122, Aug. 30, 1988; 55 FR 28380, July 11, 1990; 65 FR 1780, Jan. 12, 2000; 65 FR 56479, Sept. 19, 2000; 67 FR 9586, Mar. 4, 2002; 69 FR 13473, Mar. 23, 2004] | (a) A drug master file is a submission of information to the Food and Drug Administration by a person (the drug master file holder) who intends it to be used for one of the following purposes: To permit the holder to incorporate the information by reference when the holder submits an investigational new drug application under part 312 or submits an application or an abbreviated application or an amendment or supplement to them under this part, or to permit the holder to authorize other persons to rely on the information to support a submission to FDA without the holder having to disclose the information to the person. FDA ordinarily neither independently reviews drug master files nor approves or disapproves submissions to a drug master file. Instead, the agency customarily reviews the information only in the context of an application under part 312 or this part. A drug master file may contain information of the kind required for any submission to the agency, including information about the following: (1) [Reserved] (2) Drug substance, drug substance intermediate, and materials used in their preparation, or drug product; (3) Packaging materials; (4) Excipient, colorant, flavor, essence, or materials used in their preparation; (5) FDA-accepted reference information. (A person wishing to submit information and supporting data in a drug master file (DMF) that is not covered by Types II through IV DMF's must first submit a letter of intent to the Drug Master File Staff, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266.) FDA will then contact the person to discuss the proposed submission. (b) An investigational new drug application or an application, abbreviated application, amendment, or supplement may incorporate by reference all or part of the contents of any drug master file in support of the submission if the holder authorizes the incorporation in writing. Each incorporation by reference is required to describe the incorporated material by name, reference number, volume, and page… | |||
| 21:21:5.0.1.1.4.7.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | G | Subpart G—Miscellaneous Provisions | § 314.430 Availability for public disclosure of data and information in an application or abbreviated application. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 55 FR 11580, Mar. 29, 1990; 57 FR 17996, Apr. 28, 1992; 61 FR 51530, Oct. 2, 1996; 64 FR 26698, May 13, 1998; 64 FR 402, Jan. 5, 1999; 66 FR 1832, Jan. 10, 2001; 68 FR 24879, May 9, 2003; 69 FR 18766, Apr. 8, 2004; 73 FR 39610, July 10, 2008; 88 FR 45066, July 14, 2023] | (a) The Food and Drug Administration will determine the public availability of any part of an application or abbreviated application under this section and part 20 of this chapter. For purposes of this section, the application or abbreviated application includes all data and information submitted with or incorporated by reference in the application or abbreviated application, including investigational new drug applications, drug master files under § 314.420, supplements submitted under § 314.70 or § 314.97, reports under § 314.80 or § 314.98, and other submissions. For purposes of this section, safety and effectiveness data include all studies and tests of a drug on animals and humans and all studies and tests of the drug for identity, stability, purity, potency, and bioavailability. (b) FDA will not publicly disclose the existence of an application or abbreviated application before an approval letter is sent to the applicant under § 314.105 or tentative approval letter is sent to the applicant under § 314.107, unless the existence of the application or abbreviated application has been previously publicly disclosed or acknowledged. (c) If the existence of an unapproved application or abbreviated application has not been publicly disclosed or acknowledged, no data or information in the application or abbreviated application is available for public disclosure. (d)(1) If the existence of an application or abbreviated application has been publicly disclosed or acknowledged before the agency sends an approval letter to the applicant, no data or information contained in the application or abbreviated application is available for public disclosure before the agency sends an approval letter, but the Commissioner may, in his or her discretion, disclose a summary of selected portions of the safety and effectiveness data that are appropriate for public consideration of a specific pending issue; for example, for consideration of an open session of an FDA advisory committee. (2) Notwithstanding paragraph (d)(1) of this se… | |||
| 21:21:5.0.1.1.4.7.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | G | Subpart G—Miscellaneous Provisions | § 314.440 Addresses for applications and abbreviated applications. | FDA | [50 FR 7493, Feb. 22, 1985, as amended at 50 FR 21238, May 23, 1985; 55 FR 11581, Mar. 29, 1990; 57 FR 17997, Apr. 28, 1992; 58 FR 47352, Sept. 8, 1993; 62 FR 43639, Aug. 15, 1997; 69 FR 13473, Mar. 23, 2004; 70 FR 14981, Mar. 24, 2005; 73 FR 39610, July 10, 2008; 74 FR 13113, Mar. 26, 2009; 75 FR 37295, June 29, 2010; 80 FR 18091, Apr. 3, 2015; 84 FR 6673, Feb. 28, 2019] | (a) Applicants shall send applications, abbreviated applications, and other correspondence relating to matters covered by this part, except for products listed in paragraph (b) of this section, to the appropriate office identified below: (1) Except as provided in paragraph (a)(4) of this section, an application under § 314.50 or § 314.54 submitted for filing should be directed to the Central Document Room, 5901-B Ammendale Rd., Beltsville, MD 20705-1266. Applicants may obtain information about folders for binding applications on the Internet at http://www.fda.gov/cder/ddms/binders.htm. After FDA has filed the application, the agency will inform the applicant which division is responsible for the application. Amendments, supplements, resubmissions, requests for waivers, and other correspondence about an application that has been filed should be addressed to 5901-B Ammendale Rd., Beltsville, MD 20705-1266, to the attention of the appropriate division. (2) Except as provided in paragraph (a)(4) of this section, an abbreviated application under § 314.94, and amendments, supplements, and resubmissions should be directed to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705-1266. This includes items sent by parcel post or overnight courier service. Correspondence not associated with an abbreviated application also should be addressed to 5901-B Ammendale Rd., Beltsville, MD 20705-1266. (3) A request for an opportunity for a hearing under § 314.110 on the question of whether there are grounds for denying approval of an application, except an application under paragraph (b) of this section, should be directed to the Associate Director for Policy (HFD-5). (4) The field copy of an application, an abbreviated application, amendments, supplements, resubmissions, requests for waivers, and other correspondence about an application and an abbreviated application shall be sent to the applicant's home FDA district office, except that a … | |||
| 21:21:5.0.1.1.4.7.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | G | Subpart G—Miscellaneous Provisions | § 314.445 Guidance documents. | FDA | [65 FR 56480, Sept. 19, 2000, as amended at 74 FR 13113, Mar. 26, 2009] | (a) FDA has made available guidance documents under § 10.115 of this chapter to help you to comply with certain requirements of this part. (b) The Center for Drug Evaluation and Research (CDER) maintains a list of guidance documents that apply to CDER's regulations. The list is maintained on the Internet and is published annually in the Federal Register. A request for a copy of the CDER list should be directed to the Office of Training and Communications, Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002. | |||
| 21:21:5.0.1.1.4.8.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.500 Scope. | FDA | [57 FR 58958, Dec. 11, 1992, as amended at 64 FR 402, Jan. 5, 1999] | This subpart applies to certain new drug products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit to patients over existing treatments (e.g., ability to treat patients unresponsive to, or intolerant of, available therapy, or improved patient response over available therapy). | |||
| 21:21:5.0.1.1.4.8.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.510 Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. | FDA | FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing that the drug product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity. Approval under this section will be subject to the requirement that the applicant study the drug further, to verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome. Postmarketing studies would usually be studies already underway. When required to be conducted, such studies must also be adequate and well-controlled. The applicant shall carry out any such studies with due diligence. | ||||
| 21:21:5.0.1.1.4.8.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.520 Approval with restrictions to assure safe use. | FDA | (a) If FDA concludes that a drug product shown to be effective can be safely used only if distribution or use is restricted, FDA will require such postmarketing restrictions as are needed to assure safe use of the drug product, such as: (1) Distribution restricted to certain facilities or physicians with special training or experience; or (2) Distribution conditioned on the performance of specified medical procedures. (b) The limitations imposed will be commensurate with the specific safety concerns presented by the drug product. | ||||
| 21:21:5.0.1.1.4.8.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.530 Withdrawal procedures. | FDA | [57 FR 58958, Dec. 11, 1992, as amended at 64 FR 402, Jan. 5, 1999] | (a) For new drugs approved under §§ 314.510 and 314.520, FDA may withdraw approval, following a hearing as provided in part 15 of this chapter, as modified by this section, if: (1) A postmarketing clinical study fails to verify clinical benefit; (2) The applicant fails to perform the required postmarketing study with due diligence; (3) Use after marketing demonstrates that postmarketing restrictions are inadequate to assure safe use of the drug product; (4) The applicant fails to adhere to the postmarketing restrictions agreed upon; (5) The promotional materials are false or misleading; or (6) Other evidence demonstrates that the drug product is not shown to be safe or effective under its conditions of use. (b) Notice of opportunity for a hearing. The Director of the Center for Drug Evaluation and Research will give the applicant notice of an opportunity for a hearing on the Center's proposal to withdraw the approval of an application approved under § 314.510 or § 314.520. The notice, which will ordinarily be a letter, will state generally the reasons for the action and the proposed grounds for the order. (c) Submission of data and information. (1) If the applicant fails to file a written request for a hearing within 15 days of receipt of the notice, the applicant waives the opportunity for a hearing. (2) If the applicant files a timely request for a hearing, the agency will publish a notice of hearing in the Federal Register in accordance with §§ 12.32(e) and 15.20 of this chapter. (3) An applicant who requests a hearing under this section must, within 30 days of receipt of the notice of opportunity for a hearing, submit the data and information upon which the applicant intends to rely at the hearing. (d) Separation of functions. Separation of functions (as specified in § 10.55 of this chapter) will not apply at any point in withdrawal proceedings under this section. (e) Procedures for hearings. Hearings held under this section will be conducted in accordance with the provisions of part 15 … | |||
| 21:21:5.0.1.1.4.8.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.540 Postmarketing safety reporting. | FDA | Drug products approved under this program are subject to the postmarketing recordkeeping and safety reporting applicable to all approved drug products, as provided in §§ 314.80 and 314.81. | ||||
| 21:21:5.0.1.1.4.8.1.6 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.550 Promotional materials. | FDA | For drug products being considered for approval under this subpart, unless otherwise informed by the agency, applicants must submit to the agency for consideration during the preapproval review period copies of all promotional materials, including promotional labeling as well as advertisements, intended for dissemination or publication within 120 days following marketing approval. After 120 days following marketing approval, unless otherwise informed by the agency, the applicant must submit promotional materials at least 30 days prior to the intended time of initial dissemination of the labeling or initial publication of the advertisement. | ||||
| 21:21:5.0.1.1.4.8.1.7 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | H | Subpart H—Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses | § 314.560 Termination of requirements. | FDA | If FDA determines after approval that the requirements established in § 314.520, § 314.530, or § 314.550 are no longer necessary for the safe and effective use of a drug product, it will so notify the applicant. Ordinarily, for drug products approved under § 314.510, these requirements will no longer apply when FDA determines that the required postmarketing study verifies and describes the drug product's clinical benefit and the drug product would be appropriate for approval under traditional procedures. For drug products approved under § 314.520, the restrictions would no longer apply when FDA determines that safe use of the drug product can be assured through appropriate labeling. FDA also retains the discretion to remove specific postapproval requirements upon review of a petition submitted by the sponsor in accordance with § 10.30. | ||||
| 21:21:5.0.1.1.4.9.1.1 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.600 Scope. | FDA | This subpart applies to certain new drug products that have been studied for their safety and efficacy in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. This subpart applies only to those new drug products for which: Definitive human efficacy studies cannot be conducted because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substance; and field trials to study the product's effectiveness after an accidental or hostile exposure have not been feasible. This subpart does not apply to products that can be approved based on efficacy standards described elsewhere in FDA's regulations (e.g., accelerated approval based on surrogate markers or clinical endpoints other than survival or irreversible morbidity), nor does it address the safety evaluation for the products to which it does apply. | ||||
| 21:21:5.0.1.1.4.9.1.2 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.610 Approval based on evidence of effectiveness from studies in animals. | FDA | (a) FDA may grant marketing approval for a new drug product for which safety has been established and for which the requirements of § 314.600 are met based on adequate and well-controlled animal studies when the results of those animal studies establish that the drug product is reasonably likely to produce clinical benefit in humans. In assessing the sufficiency of animal data, the agency may take into account other data, including human data, available to the agency. FDA will rely on the evidence from studies in animals to provide substantial evidence of the effectiveness of these products only when: (1) There is a reasonably well-understood pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by the product; (2) The effect is demonstrated in more than one animal species expected to react with a response predictive for humans, unless the effect is demonstrated in a single animal species that represents a sufficiently well-characterized animal model for predicting the response in humans; (3) The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity; and (4) The data or information on the kinetics and pharmacodynamics of the product or other relevant data or information, in animals and humans, allows selection of an effective dose in humans. (b) Approval under this subpart will be subject to three requirements: (1) Postmarketing studies. The applicant must conduct postmarketing studies, such as field studies, to verify and describe the drug's clinical benefit and to assess its safety when used as indicated when such studies are feasible and ethical. Such postmarketing studies would not be feasible until an exigency arises. When such studies are feasible, the applicant must conduct such studies with due diligence. Applicants must include as part of their application a plan or approach to postmarketing study commitments in the event such studies become ethical and f… | ||||
| 21:21:5.0.1.1.4.9.1.3 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.620 Withdrawal procedures. | FDA | (a) Reasons to withdraw approval. For new drugs approved under this subpart, FDA may withdraw approval, following a hearing as provided in part 15 of this chapter, as modified by this section, if: (1) A postmarketing clinical study fails to verify clinical benefit; (2) The applicant fails to perform the postmarketing study with due diligence; (3) Use after marketing demonstrates that postmarketing restrictions are inadequate to ensure safe use of the drug product; (4) The applicant fails to adhere to the postmarketing restrictions applied at the time of approval under this subpart; (5) The promotional materials are false or misleading; or (6) Other evidence demonstrates that the drug product is not shown to be safe or effective under its conditions of use. (b) Notice of opportunity for a hearing. The Director of the Center for Drug Evaluation and Research (CDER) will give the applicant notice of an opportunity for a hearing on CDER's proposal to withdraw the approval of an application approved under this subpart. The notice, which will ordinarily be a letter, will state generally the reasons for the action and the proposed grounds for the order. (c) Submission of data and information. (1) If the applicant fails to file a written request for a hearing within 15 days of receipt of the notice, the applicant waives the opportunity for a hearing. (2) If the applicant files a timely request for a hearing, the agency will publish a notice of hearing in the Federal Register in accordance with §§ 12.32(e) and 15.20 of this chapter. (3) An applicant who requests a hearing under this section must, within 30 days of receipt of the notice of opportunity for a hearing, submit the data and information upon which the applicant intends to rely at the hearing. (d) Separation of functions. Separation of functions (as specified in § 10.55 of this chapter) will not apply at any point in withdrawal proceedings under this section. (e) Procedures for hearings. Hearings held under this section will be conducted in… | ||||
| 21:21:5.0.1.1.4.9.1.4 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.630 Postmarketing safety reporting. | FDA | Drug products approved under this subpart are subject to the postmarketing recordkeeping and safety reporting requirements applicable to all approved drug products, as provided in §§ 314.80 and 314.81. | ||||
| 21:21:5.0.1.1.4.9.1.5 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.640 Promotional materials. | FDA | For drug products being considered for approval under this subpart, unless otherwise informed by the agency, applicants must submit to the agency for consideration during the preapproval review period copies of all promotional materials, including promotional labeling as well as advertisements, intended for dissemination or publication within 120 days following marketing approval. After 120 days following marketing approval, unless otherwise informed by the agency, the applicant must submit promotional materials at least 30 days prior to the intended time of initial dissemination of the labeling or initial publication of the advertisement. | ||||
| 21:21:5.0.1.1.4.9.1.6 | 21 | Food and Drugs | I | D | 314 | PART 314—APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG | I | Subpart I—Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible | § 314.650 Termination of requirements. | FDA | If FDA determines after approval under this subpart that the requirements established in §§ 314.610(b)(2), 314.620, and 314.630 are no longer necessary for the safe and effective use of a drug product, FDA will so notify the applicant. Ordinarily, for drug products approved under § 314.610, these requirements will no longer apply when FDA determines that the postmarketing study verifies and describes the drug product's clinical benefit. For drug products approved under § 314.610, the restrictions would no longer apply when FDA determines that safe use of the drug product can be ensured through appropriate labeling. FDA also retains the discretion to remove specific postapproval requirements upon review of a petition submitted by the sponsor in accordance with § 10.30 of this chapter. | ||||
| 9:9:2.0.2.1.15.0.7.1 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.1 Disposition of condemned products at official establishments having tanking facilities; sealing of tanks. | FSIS | (a) Carcasses, parts of carcasses, and other products condemned at official establishments having facilities for tanking shall, except as provided in paragraph (c) of this section or elsewhere in this part, be disposed of by tanking as follows: (1) The lower opening of the tank shall first be sealed securely by a Program employee, except when permanently connected with a blow line; then the condemned products shall be placed in the tank in his presence, after which the upper opening shall also be sealed securely by such employee, who shall then see that the contents of the tank are subjected to sufficient heating for sufficient time to effectively destroy the contents for human food purposes. (2) The use of equipment such as crushers or hashers for pretanking preparation of condemned products in the inedible products department has been found to give inedible character and appearance to the material. Accordingly, if condemned products are so crushed or hashed, conveying systems, rendering tanks, and other equipment used in the further handling of crushed or hashed material need not be locked or sealed during the tanking operations. If the rendering tanks or other equipment contain condemned material not so crushed or hashed, the equipment shall be sealed as prescribed in paragraph (a)(1) of this section. If the crushed or hashed material is not rendered in the establishment where produced, it shall be denatured as provided for in § 314.3 before leaving such establishment. (b) The seals of tanks shall be broken only by a Program employee and only after the contents of the tanks have been treated as provided in paragraph (a) of this section. The rendered fat derived from condemned material shall be held until a Program employee shall have had an opportunity to determine whether it conforms with the requirements of this section. Samples shall be taken by Program employees as often as is necessary to determine whether the rendered fat is effectually denatured. (c) Carcasses of animals condemned under § 309.3 of t… | ||||||
| 9:9:2.0.2.1.15.0.7.10 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.10 Livers condemned because of parasitic infestation and for other causes; conditions for disposal for purposes other than human food. | FSIS | [41 FR 23701, June 11, 1976] | (a) Livers condemned on account of hydatid cysts shall be disposed of by tanking pursuant to the provisions of § 314.1 of this subchapter if condemned at official establishments having facilities for tanking; otherwise they shall be destroyed pursuant to the provisions of § 314.3 of this subchapter. (b) Livers condemned because of parasites other than hydatid cysts; and livers condemned because of telangiectasis, angioma, “sawdust” condition, cirrhosis, carotenosis, or other nonmalignant change, benign abscesses, or contamination, when these conditions are not associated with infectious diseases in the carcasses, may be shipped from an official establishment only for purposes other than human food, and only if all tissue affected with abscesses is removed and destroyed within the establishment, and all livers are processed and denatured, with any agent prescribed in § 325.13(a)(1) or (2) or (5), and in accordance with § 325.13(a)(6) of this subchapter. This provision for movement from an official establishment is made solely under the Federal Meat Inspection Act and is not intended to relieve or modify any other applicable requirements under any other law regarding the movement of such articles, for purposes other than use as human food. (c) Livers condemned because of conditions described in paragraph (b) of this section shall be in containers plainly marked “inedible”. | |||||
| 9:9:2.0.2.1.15.0.7.11 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.11 Handling of certain condemned products for purposes other than human food. | FSIS | [35 FR 15575, Oct. 3, 1970, as amended at 36 FR 11639, June 17, 1971; 36 FR 11903, June 23, 1971] | Condemned carcasses of animals affected with one or more of the following conditions may be shipped from an official establishment only for purposes other than human food and only if permission therefor is obtained from the circuit supervisor: Anasarca, Ocular Squamous Cell Carcinoma (after removal of neoplastic tissue), emaciation, eosinophilic myositis, immaturity, nonseptic bruises and injuries, and sarcosporidiosis. This provision also applies to unborn calves and to products such as paunches and udders when they have not been handled as required under this subchapter for products for human food purposes; provided, such articles have not been condemned for other pathological reasons. Such permission will be granted only if all parts to be so used will be promptly handled, freely slashed and adequately identified as required by § 325.13(a)(2) of this subchapter. The slashing, identification and packing of the product shall be accomplished in an inedible product area under the supervision of an inspector. Facilities must be adequate so that the carcasses or parts saved under these provisions are not contaminated with pus, manure, septic, or toxic materials, or similar substances. The operation must not result in unsanitary conditions within the establishment. | |||||
| 9:9:2.0.2.1.15.0.7.2 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.2 Tanking and other facilities for inedible products to be separate from edible product facilities. | FSIS | [64 FR 56416, Oct. 20, 1999] | All tanks and equipment used for rendering, otherwise preparing, or storing inedible products must be in rooms or compartments separate from those used for preparing or storing edible products. There may be a connection between rooms or compartments containing inedible products and those containing edible products as long as it does not cause the adulteration of edible product or create insanitary conditions. | |||||
| 9:9:2.0.2.1.15.0.7.3 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.3 Disposition of condemned products at official establishments having no tanking facilities. | FSIS | (a) Carcasses, parts of carcasses, and other products condemned at an official establishment which has no facilities for tanking shall, except as provided in paragraph (b) of this section or elsewhere in this part, be destroyed in the presence of an inspector by incineration, or denatured with crude carbolic acid, or cresylic disinfectant, or a formula consisting of one part FD&C No. 3 green coloring, 40 parts water, 40 parts liquid detergent, and 40 parts oil of citronella or any other proprietary material approved by the Administrator in specific cases. When such product is to be denatured, it shall be freely slashed before the denaturing agent is applied, except that, in the case of dead animals that have not been dressed, the denaturant may be applied by injection. The denaturant must be deposited in all portions of the carcass or product to the extent necessary to preclude its use for food purposes. (b) All carcasses and parts condemned on account of anthrax, as identified in § 310.9(b) of this subchapter, at official establishments which are not equipped with tanking facilities shall be disposed of by (1) complete incineration, or (2) by thorough denaturing with crude carbolic acid, or cresylic disinfectant, and then disposed of in accordance with the requirements of the particular State or municipal authorities, who shall be notified immediately by the area supervisor. | ||||||
| 9:9:2.0.2.1.15.0.7.4 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.4 Suppression of odors in preparing inedible products. | FSIS | [64 FR 56416, Oct. 20, 1999] | Tanks, fertilizer driers, and other equipment used in the preparation of inedible product must be operated in a manner that will suppress odors incident to such preparation which could adulterate edible product or create insanitary conditions. | |||||
| 9:9:2.0.2.1.15.0.7.5 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.5 Inedible rendered fats prepared at official establishments. | FSIS | [35 FR 15575, Oct. 3, 1970, as amended at 53 FR 24679, June 30, 1988] | Except as provided in § 325.11(b) of this subchapter, rendered animal fat derived from condemned or other inedible materials at official establishments shall be denatured to effectually distinguish it from an edible product, either with low grade offal during the rendering or by adding to, and mixing thoroughly with, such fat, denaturing oil, No. 2 fuel oil, or brucine dissolved in a mixture of alcohol and pine oil or oil of rosemary, and may be shipped in commerce in accordance with § 325.11(c) of this subchapter. | |||||
| 9:9:2.0.2.1.15.0.7.6 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.6 Inedible fats from outside official establishments. | FSIS | [35 FR 15575, Oct. 3, 1970, as amended at 53 FR 24679, June 30, 1988] | Except as provided in § 325.11(b) of this subchapter, inedible fats from outside the premises of any official establishment shall not be received into an official establishment except into the tank room provided for inedible products, and then only when they have been denatured in accordance with § 314.5 and are marked in accordance with § 316.15 of this subchapter, and when their receipt into the tank room produces no insanitary condition on the premises; nor shall such fats be received in such volume as interferes with prompt disposal of condemned or other inedible material produced at the establishment. When received, they shall not enter any room or compartment used for edible products. | |||||
| 9:9:2.0.2.1.15.0.7.7 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.7 Carcasses of livestock condemned on ante-mortem inspection not to pass through edible product areas. | FSIS | Carcasses of livestock which have been condemned on ante-mortem inspection shall not be taken through rooms or compartments in which an edible product is prepared, handled, or stored. | ||||||
| 9:9:2.0.2.1.15.0.7.8 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.8 Dead animal carcasses. | FSIS | (a) With the exception of dead livestock which have died en route and are received with livestock for slaughter at an official establishment, no dead animal or part of the carcass of any livestock that died otherwise than by slaughter may be brought on the premises of an official establishment unless advance permission therefore is obtained from the circuit supervisor. (b) Under no circumstances shall the carcasses of any animal which has died otherwise than by slaughter, or any part thereof, be brought into any room or compartment in which any edible product is prepared, handled, or stored. | ||||||
| 9:9:2.0.2.1.15.0.7.9 | 9 | Animals and Animal Products | III | A | 314 | PART 314—HANDLING AND DISPOSAL OF CONDEMNED OR OTHER INEDIBLE PRODUCTS AT OFFICIAL ESTABLISHMENTS | § 314.9 Specimens for educational, research, and other nonfood purposes; permits for, required. | FSIS | [35 FR 15575, Oct. 3, 1970, as amended at 38 FR 18665, July 13, 1973; 39 FR 36000, Oct. 7, 1974] | (a) Specimens of condemned or other inedible materials, including embryos and specimens of animal parasites, may be released for educational, research, or other nonfood purposes under permit issued by the inspector in charge: Provided, That the person desiring such specimens makes a written application to the inspector in charge for such permit on Form MP-403-10 and arranges with and receives permission from the official establishment to obtain the specimens. Permits shall be issued for a period not longer than 1 year. The permit may be revoked by the inspector in charge if the specimens are not used as stated in the application, or if the collection or handling of the specimens interferes with inspection or the maintenance of sanitary conditions in the establishment. (b) The specimens referred to in paragraph (a) of this section shall be collected and handled only at such time and place and in such manner as not to interfere with the inspection or to cause any objectionable condition and shall be identified as inedible when they leave the establishment. |
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title_number INTEGER,
title_name TEXT,
chapter TEXT,
subchapter TEXT,
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