(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) Submission of an amendment to an original NDA, efficacy supplement, or resubmission of an NDA or efficacy supplement that is not a major amendment will not extend the initial review cycle. FDA may, at its discretion, review such an amendment during the initial review cycle or defer review until the subsequent review cycle.

(4) Submission of a major amendment to a manufacturing supplement within 2 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 2 months. FDA may instead defer review of the amendment until the subsequent review cycle. If the agency extends the initial review cycle for a manufacturing supplement under this paragraph, the division responsible for reviewing the supplement will notify the applicant of the extension. The initial review cycle for a manufacturing 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.

(5) Submission of an amendment to a supplement other than an efficacy or manufacturing supplement will not extend the initial review cycle. FDA may, at its discretion, review such an amendment during the initial review cycle or defer review until the subsequent review cycle.

(6) A major amendment may not include data to support an indication or claim that was not included in the original NDA, supplement, or resubmission, but it may include data to support a minor modification of an indication or claim that was included in the original NDA, supplement, or resubmission.

(7) When FDA defers review of an amendment until the subsequent review cycle, the agency will notify the applicant of the deferral in the complete response letter sent to the applicant under §314.110 of this part.

(c) Limitation on certain amendments.

(1) An unapproved NDA may not be amended if all of the following conditions apply:

(i) The unapproved NDA is for a drug for which a previous NDA has been approved and granted a period of exclusivity in accordance with section 505(c)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act that has not expired;

(ii) The applicant seeks to amend the unapproved NDA to include a published report of an investigation that was conducted or sponsored by the applicant entitled to exclusivity for the drug;

(iii) The applicant has not obtained a right of reference or use to the investigation described in paragraph (c)(1)(ii) of this section; and

(iv) The report of the investigation described in paragraph (c)(1)(ii) of this section would be essential to the approval of the unapproved NDA.

(2) The submission of an amendment described in paragraph (c)(1) of this section will cause the unapproved NDA to be deemed to be withdrawn by the applicant under §314.65 on the date of receipt by FDA of the amendment. The amendment will be considered a resubmission of the NDA, which may not be accepted except as provided in accordance with section 505(c)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act.

(d) Field copy. The applicant must submit a field copy of each amendment to a section of the NDA described in §314.50(d)(1). The 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.

(e) Different drug. An applicant may not amend a 505(b)(2) application to seek approval of a drug that is a different drug from the drug in the original submission of the 505(b)(2) application. For purposes of this paragraph (e), a drug is a different drug if it has been modified to have a different active ingredient, different route of administration, different dosage form, or difference in excipients that requires either a separate clinical study to establish safety or effectiveness or, for topical products, that requires a separate in vivo demonstration of bioequivalence. However, notwithstanding the limitation described in this paragraph (e), an applicant may amend the 505(b)(2) application to seek approval of a different strength.

(f) Patent certification requirements.

(1) An amendment to a 505(b)(2) application is required to contain an appropriate patent certification or statement described in §314.50(i) or a recertification for a previously submitted paragraph IV certification if approval is sought for any of the following types of amendments:

(i) To add a new indication or other condition of use;

(ii) To add a new strength;

(iii) To make other than minor changes in product formulation; or

(iv) To change the physical form or crystalline structure of the active ingredient.

(2) If the amendment to the 505(b)(2) application does not contain a patent certification or statement, the applicant must verify that the proposed change described in the amendment is not one of the types of amendments described in paragraph (f)(1) of this section.

[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]