[Code of Federal Regulations] [Title 21, Volume 5] [Revised as of April 1, 2001] From the U.S. Government Printing Office via GPO Access [CITE: 21CFR314.125] [Page 149-150] TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--Continued PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG--Table of Contents Subpart D--FDA Action on Applications and Abbreviated Applications Sec. 314.125 Refusal to approve an application. (a) The Food and Drug Administration will refuse to approve the application and for a new drug give the applicant written notice of an opportunity for a hearing under Sec. 314.200 on the question of whether there are grounds for denying approval of the application under section 505(d) of the act, if: (1) FDA sends the applicant an approvable or a not approvable letter under Sec. 314.110 or Sec. 314.120; (2) The applicant requests an opportunity for hearing for a new drug on the question of whether the application 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 application for any of the following reasons: (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 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 Sec. 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 false or misleading in any particular. (7) The application contains an untrue statement of a material fact. (8) The drug product's proposed labeling does not comply with the requirements for labels and labeling in part 201. (9) The application does not contain bioavailability or bioequivalence data required under part 320 of this chapter. (10) A reason given in a letter refusing to file the application under Sec. 314.101(d), if the deficiency is not corrected. (11) The drug will be manufactured or processed in whole or in part in an establishment that is not registered and not exempt from registration under section 510 of the act and part 207. (12) The applicant does not permit a properly authorized officer or employee of the Department of Health and Human Services an adequate opportunity to inspect the facilities, controls, and any records relevant to the application. (13) The methods to be used in, and the facilities and controls used for, the [[Page 150]] manufacture, processing, packing, or holding of the drug substance or the drug product do not comply with the current good manufacturing practice regulations in parts 210 and 211. (14) The application does not contain an explanation of the omission of a report of any investigation of the drug product sponsored by the applicant, or an explanation of the omission of other information about the drug pertinent to an evaluation of the application that is received or otherwise obtained by the applicant from any source. (15) A nonclinical laboratory study that is described in the application and that is essential to show that the drug is safe for use under the conditions prescribed, recommended, or suggested in its proposed labeling was not conducted in compliance with the good laboratory practice regulations in part 58 of this chapter and no reason for the noncompliance is provided or, if it is, the differences between the practices used in conducting the study and the good laboratory practice regulations do not support the validity of the study. (16) Any clinical investigation involving human subjects described in the application, subject to the institutional review board regulations in part 58 of this chapter or informed consent regulations in part 50 of this chapter, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected. (17) The applicant or contract research organization that conducted a bioavailability or bioequivalence study described in Sec. 320.38 or Sec. 320.63 of this chapter that is contained in the application refuses to permit an inspection of facilities or records relevant to the study by a properly authorized officer or employee of the Department of Health and Human Services or refuses to submit reserve samples of the drug products used in the study when requested by FDA. (18) For a new drug, the application failed to contain the patent information required by section 505(b)(1) of the act. (c) For drugs intended to treat life-threatening or severely- debilitating illnesses that are developed in accordance with Secs. 312.80 through 312.88 of this chapter, the criteria contained in paragraphs (b) (3), (4), and (5) of this section shall be applied according to the considerations contained in Sec. 312.84 of this chapter. [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]