EFFECTIVE DATE NOTE: At 63 FR 5252, Feb. 2, 1998, §314.300 was amended in the introductory text of paragraph (b)(6) by adding a new sentence after the first sentence, effective Feb. 2, 1999.

Subpart G-Miscellaneous Provisions

SOURCE: 50 FR 7493, Feb. 22, 1985, unless otherwise noted. Redesignated at 57 FR 17983, Apr. 28, 1992.

§314.410 Imports and exports of new drugs and antibiotics.

(a) Imports. (1) A new drug or an antibiotic may be imported into the United States if: (i) It is the subject of an approved application under this part or, in the case of an antibiotic not exempt from certification under part 433, it is also certified or released; 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 or an antibiotic may be exported if it is the subject of an approved application under this part, and, in the case of an antibiotic, it is certified or released, 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 specifications of, and is shipped with a copy of the labeling required for, the approved drug product.

(3) An antibiotic drug product or drug substance that is subject to certification under section 507 of the act, but which has not been certified or released, may be exported under section 801(e) of the act if it meets the following conditions:

(1) It meets the specifications of the foreign purchaser;

(ii) It is not in conflict with the laws of the country to which it is intended for export;

(iii) It is labeled on the outside of the shipping package that it is intended for export; and

(iv) It is not sold or offered for sale in the United States.

§ 314.420 Drug master files.

(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 approves 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:

dis

(1) Manufacturing site, facilities, operating procedures, and personnel (because an FDA on-site inspection of a foreign drug manufacturing facility presents unique problems of planning and travel not presented by an inspection of a domestic manufacturing facility, this information is only recommended for foreign manufacturing establishments);

(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 I through IV DMF's must first submit a letter of intent to the Drug Master File Staff, Food and Drug Administration, 12420 Parklawn Dr., Rm. 2-14, Rockville, MD 20852. 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 number of the drug master file.

(c) A drug master file is required to be submitted in two copies. The agency has prepared under §10.90(b) a guideline that provides information about how to prepare a well-organized drug master file. If the drug master file holder adds, changes, or deletes any information in the file, the holder shall notify in writing, each person authorized to reference that information. Any addition, change, or deletion of information in a drug master file (except the list required under paragraph (d) of this section) is required to be submitted in two copies and to describe by name, reference number, volume, and page number the information affected in the drug master file.

(d) The drug master file is required to contain a complete list of each person currently authorized to incorporate by reference any information in the file, identifying by name, reference number, volume, and page number the information that each person is authorized to incorporate. If the holder restricts the authorization to particular drug products, the list is required to include the name of each drug product and the application number, if known, to which the authorization applies.

(e) The public availability of data and information in a drug master file, including the availability of data and information in the file to a person au

thorized to reference the file, is determined under part 20 and §314.430.

(Collection of information requirements approved by the Office of Management and Budget under control number 0910-0001)

[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]

§314.430 Availability for public disclosure of data and information in an application or abbreviated application.

(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 approvable letter is sent to the applicant under §314.110, unless the existence of the application or abbreviated application has been previously publicly disclosed or acknowledged. The Center for Drug Evaluation and Research will maintain and make available for public disclosure a list of applications or abbreviated applications for which the agency has sent an approvable letter to the applicant.

(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 section, FDA will make available to the public upon request the information in the investigational new drug application that was required to be filed in Docket Number 95S-0158 in the Dockets Management Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857, for investigations involving an exception from informed consent under $50.24 of this chapter. Persons wishing to request this information shall submit a request under the Freedom of Information Act.

(e) After FDA sends an approval letter to the applicant, the following data and information in the application or abbreviated application are immediately available for public disclosure, unless the applicant shows that extraordinary circumstances exist. A list of approved applications and abbreviated applications, entitled "Approved Drug Products with Therapeutic Equivalence Evaluations," is available from the Government Printing Office, Washington, DC 20402. This list is updated monthly.

(1) [Reserved]

(2) If the application applies to a new drug, all safety and effectiveness data previously disclosed to the public as set forth in §20.81 and a summary or summaries of the safety and effectiveness data and information submitted with or incorporated by reference in the application. The summaries do not constitute the full reports of investigations under section 505(b)(1) of the act (21 U.S.C. 355(b)(1)) on which the safety or effectiveness of the drug may be approved. The summaries consist of the following:

(i) For an application approved before July 1, 1975, internal agency records that describe safety and effectiveness data and information, for example, a summary of the basis for approval or internal reviews of the data and information, after deletion of the following:

(a) Names and any information that would identify patients or test subjects or investigators.

(b) Any inappropriate gratuitous comments unnecessary to an objective analysis of the data and information.

(ii) For an application approved on or after July 1, 1975, a Summary Basis of Approval (SBA) document that contains a summary of the safety and effectiveness data and information evaluated by FDA during the drug approval process. The SBA is prepared in one of the following ways:

(a) Before approval of the application, the applicant may prepare a draft SBA which the Center for Drug Evaluation and Research will review and may revise. The draft may be submitted with the application or as an amendment.

(b) The Center for Drug Evaluation and Research may prepare the SBA.

(3) A protocol for a test or study, unless it is shown to fall within the exemption established for trade secrets and confidential commercial information in § 20.61.

(4) Adverse reaction reports, product experience reports, consumer complaints, and other similar data and information after deletion of the following:

(i) Names and any information that would identify the person using the product.

(ii) Names and any information that would identify any third party involved with the report, such as a physician or hospital or other institution.

(5) A list of all active ingredients and any inactive ingredients previously disclosed to the public as set forth in § 20.81.

(6) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption established for trade secrets and confidential commercial information in § 20.61.

(7) All correspondence and written summaries of oral discussions between FDA and the applicant relating to the application, under the provisions of part 20.

(8) All records showing the testing of an action on a particular lot of a certifiable antibiotic by FDA.

(f) All safety and effectiveness data and information which have been submitted in an application and which have not previously been disclosed to the public are available to the public, upon request, at the time any one of the following events occurs unless extraordinary circumstances are shown:

(1) No work is being or will be undertaken to have the application approved.

(2) A final determination is made that the application is not approvable and all legal appeals have been exhausted.

(3) Approval of the application is withdrawn and all legal appeals have been exhausted.

(4) A final determination has been made that the drug is not a new drug.

(5) For applications submitted under section 505(b) of the act, the effective date of the approval of the first abbreviated application submitted under section 505(j) of the act which refers to such drug, or the date on which the approval of an abbreviated application under section 505(j) of the act which refers to such drug could be made effective if such an abbreviated application had been submitted.

(6) For applications or abbreviated applications submitted under sections 505(j), 506, and 507 of the act, when FDA sends an approval letter to the applicant.

(g) The following data and information in an application or abbreviated application are not available for public disclosure unless they have been previously disclosed to the public as set forth in §20.81 of this chapter or they relate to a product or ingredient that has been abandoned and they do not represent a trade secret or confidential commercial or financial information under § 20.61 of this chapter:

(1) Manufacturing methods or processes, including quality control procedures.

(2) Production, sales distribution, and similar data and information, except that any compilation of that data and information aggregated and prepared in a way that does not reveal data or information which is not available for public disclosure under this provision is available for public disclo

sure.

(3) Quantitative or semiquantitative formulas.

(h) The compilations of information specified in § 20.117 are available for public disclosure.

[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]

§314.440 Addresses for for applications and abbreviated applications.

(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 Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, and directed 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 Document and Records Section, 12420 Parklawn Dr., Rockville, MD 20852. Applicants may obtain folders for binding applications from the Consolidated Forms and Publications Distribution Center, Washington Commerce Center, 3222 Hubbard Rd., Landover, MD 20785. 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 directed to 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 Office of Generic Drugs (HFD-600), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Items sent

by parcel post or overnight courier service should be directed to the Office of Generic Drugs (HFD-600), Center for Drug Evaluation and Research, Food and Drug Administration, Metro Park North II, 7500 Standish Place, rm. 150, Rockville, MD 20855. Correspondence not associated with an application should be addressed specifically to the intended office or division and to the person as follows: Center for Drug Evaluation and Research, Food and Drug Administration, Attn: [insert name of person], MPN II, HFD-[insert mail code of office or division], 5600 Fishers Lane, Rockville, MD 20857. The mail code for the Office of Generic Drugs is HFD-600, the mail code for the Division of Chemistry is HFD-630, and the mail code for the Division of Bioequivalence is HFD-650.

(3) A request for an opportunity for a hearing under §314.110 or $314.120 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 foreign applicant shall send the field copy to the appropriate address identified in paragraphs (a)(1) and (a)(2) of this section.

(b) Applicants shall send applications and other correspondence relating to matters covered by this part for the drug products listed below to the Division of Product Certification (HFB240), Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, except applicants shall send a request for an opportunity for a hearing under $314.110 or $314.120 on the question of whether there are grounds for denying approval of an application to the Director, Center for Biologics Evaluation and Research (HFB-1), at the same address.

(1) Ingredients packaged together with containers intended for the collec

tion, processing, or storage of blood and blood components.

(2) Urokinase products.

(3) Plasma volume expanders and hydroxyethyl starch for leukapheresis.

[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]

§314.445 Guidelines.

(a) The Food and Drug Administration prepares guidelines under §10.90(b) to help persons comply with requirements in this part.

(b) The Center for Drug Evaluation and Research will maintain and make publicly available a list of guidelines that apply to the Center's regulations. The list states how a person can obtain a copy of each guideline. A request for a copy of the list should be directed to the CDER Executive Secretariat Staff (HFD-8), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.

[50 FR 7493, Feb. 22, 1985, as amended at 55 FR 11581, Mar. 29, 1990; 56 FR 3776, Jan. 31, 1991]

Subpart H-Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses

SOURCE: 57 FR 58958, Dec. 11, 1992, unless otherwise noted.

§ 314.500 Scope.

This subpart applies to certain new drug and antibiotic products that have been studied for their safety and effectiveness in treating serious or lifethreatening 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).

§314.510 Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical