Source: https://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm120082.htm
Timestamp: 2019-04-21 10:40:40+00:00

Document:
(1) To any person who has submitted an application, by delivering the notice in person or by sending it by registered or certified mail to the last address shown in the application.
(2) To any person who has not submitted an application but who is subject to the notice under § 310.6, by publication of the notice in the Federal Register.
(c) (1) Notice of participation and request for a hearing, and submission of studies and comments. The applicant, or any other person subject to the notice under § 310.6, who wishes to participate in a hearing, shall file with the Dockets Management Branch (HFA-305), Food and Drug Administration, Rm. 4-62, Rockville, MD 20857, (i) within 30 days after the date of the publication of the notice (or of the date of receipt of an opinion requested under paragraph (a)(3) of this section) a written notice of participation and request for a hearing and (ii) within 60 days after the date of publication of the notice, unless a different period of time is specified in the notice of opportunity for a hearing, the studies on which the person relies to justify a hearing as specified in paragraph (d) of this section. The applicant, or other person, may incorporate by reference the raw data underlying a study if the data were previously submitted to FDA as part of an application or other report.
(2) FDA will not consider data or analyses submitted after 60 days in determining whether a hearing is warranted unless they are derived from well-controlled studies begun before the date of the notice of opportunity for hearing and the results of the studies were not available within 60 days after the date of publication of the notice. Nevertheless, FDA may consider other studies on the basis of a showing by the person requesting a hearing of inadvertent omission and hardship. The person requesting a hearing shall list in the request for hearing all studies in progress, the results of which the person intends later to submit in support of the request for a hearing. The person shall submit under paragraph (c)(1)(ii) of this section a copy of the complete protocol, a list of the participating investigators, and a brief status report of the studies.
(3) Any other interested person who is not subject to the notice of opportunity for a hearing may also submit comments on the proposal to withdraw approval of the application. The comments are required to be submitted within the time and under the conditions specified in this section.
(d) The person requesting a hearing is required to submit under paragraph (c)(1)(ii) of this section the studies (including all protocols and underlying raw data) on which the person relies to justify a hearing with respect to the drug product. Except, a person who requests a hearing on the refusal to approve an application is not required to submit additional studies and analyses if the studies upon which the person relies have been submitted in the application and in the format and containing the summaries required under § 314.50.
(1) If the grounds for FDA's proposed action concern the effectiveness of the drug, each request for hearing is required to be supported only by adequate and well-controlled clinical studies meeting all of the precise requirements of § 314.126 and, for combination drug products, § 300.50, or by other studies not meeting those requirements for which a waiver has been previously granted by FDA under § 314.126. Each person requesting a hearing shall submit all adequate and well-controlled clinical studies on the drug product, including any unfavorable analyses, views, or judgments with respect to the studies. No other data, information, or studies may be submitted.
(2) The submission is required to include a factual analysis of all the studies submitted. If the grounds for FDA's proposed action concern the effectiveness of the drug, the analysis is required to specify how each study accords, on a point-by-point basis, with each criterion required for an adequate well-controlled clinical investigation established under § 314.126 and, if the product is a combination drug product, with each of the requirements for a combination drug established in § 300.50, or the study is required to be accompanied by an appropriate waiver previously granted by FDA. If a study concerns a drug or dosage form or condition of use or mode of administration other than the one in question, that fact is required to be clearly stated. Any study conducted on the final marketed form of the drug product is required to be clearly identified.
(3) Each person requesting a hearing shall submit an analysis of the data upon which the person relies, except that the required information relating either to safety or to effectiveness may be omitted if the notice of opportunity for hearing does not raise any issue with respect to that aspect of the drug; information on compliance with § 300.50 may be omitted if the drug product is not a combination drug product. FDA can most efficiently consider submissions made in the following format.
b. Partially controlled or uncontrolled studies.
2. Combinations of the individual active components.
a determination about the safety of each individual active component.
A. Individual active components: Controlled studies, with an analysis showing clearly how each study satisfies, on a point-by-point basis, each of the criteria required by § 314.126.
B. Combinations of individual active components.
1. Controlled studies with an analysis showing clearly how each study satisfies on a point-by-point basis, each of the criteria required by § 314.126. 2. An analysis showing clearly how each requirement of § 300.50 has been satisfied.
III. A summary of the data and views setting forth the medical rationale and purpose for the drug and its ingredients and the scientific basis for the conclusion that the drug and its ingredients have been proven safe and/or effective for the intended use. If there is an absence of controlled studies in the material submitted or the requirements of any element of § 300.50 or § 314.126 have not been fully met, that fact is required to be stated clearly and a waiver obtained under § 314.126 is required to be submitted.
IV. A statement signed by the person responsible for such submission that it includes in full (or incorporates by reference as permitted in § 314.200(c)(2)) all studies and information specified in § 314.200(d).
(e) Contentions that a drug product is not subject to the new drug requirements. A notice of opportunity for a hearing encompasses all issues relating to the legal status of each drug product subject to it, including identical, related, and similar drug products as defined in § 310.6. A notice of appearance and request for a hearing under paragraph (c)(1)(i) of this section is required to contain any contention that the product is not a new drug because it is generally recognized as safe and effective within the meaning of section 201(p) of the act, or because it is exempt from part or all of the new drug provisions of the act under the exemption for products marketed before June 25, 1938, contained in section 201(p) of the act or under section 107(c) of the Drug Amendments of 1962, or for any other reason. Each contention is required to be supported by a submission under paragraph (c)(1)(ii) of this section and the Commissioner of Food and Drugs will make an administrative determination on each contention. The failure of any person subject to a notice of opportunity for a hearing, including any person who manufactures or distributes an identical, related, or similar drug product as defined in § 310.6, to submit a notice of participation and request for hearing or to raise all such contentions constitutes a waiver of any contentions not raised.
(1) A contention that a drug product is generally recognized as safe and effective within the meaning of section 201(p) of the act is required to be supported by submission of the same quantity and quality of scientific evidence that is required to obtain approval of an application for the product, unless FDA has waived a requirement for effectiveness (under § 314.126) or safety, or both. The submission should be in the format and with the analyses required under paragraph (d) of this section. A person who fails to submit the required scientific evidence required under paragraph (d) waives the contention. General recognition of safety and effectiveness shall ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information.
(2) A contention that a drug product is exempt from part or all of the new drug provisions of the act under the exemption for products marketed before June 25, 1938, contained in section 201(p) of the act, or under section 107(c) of the Drug Amendments of 1962, is required to be supported by evidence of past and present quantitative formulas, labeling, and evidence of marketing. A person who makes such a contention should submit the formulas, labeling, and evidence of marketing in the following format.
A. A copy of each pertinent document or record to establish the exact quantitative formulation of the drug (both active and inactive ingredients) on the date of initial marketing of the drug.
B. A statement whether such formulation has at any subsequent time been changed in any manner. If any such change has been made, the exact date, nature, and rational for each change in formulation, including any deletion or change in the concentration of any active ingredient and/or inactive ingredient, should be stated, together with a copy of each pertinent document or record to establish the date and nature of each such change, including, but not limited to, the formula which resulted from each such change. If no such change has been made, a copy of representative documents or records showing the formula at representative points in time should be submitted to support the statement.
A. A copy of each pertinent document or record to establish the identity of each item of written, printed, or graphic matter used as labeling on the date the drug was initially marketed.
B. A statement whether such labeling has at any subsequent time been discontinued or changed in any manner. If such discontinuance or change has been made, the exact date, nature, and rationale for each discontinuance or change and a copy of each pertinent document or record to establish each such discontinuance or change should be submitted, including, but not limited to, the labeling which resulted from each such discontinuance or change. If no such discontinuance or change has been made, a copy of representative documents or records showing labeling at representative points in time should be submitted to support the statement.
A. A copy of each pertinent document or record to establish the exact date the drug was initially marketed.
B. A statement whether such marketing has at any subsequent time been discontinued. If such marketing has been discontinued, the exact date of each such discontinuance should be submitted, together with a copy of each pertinent document or record to establish each such date.
A statement signed by the person responsible for such submission, that all appropriate records have been searched and to the best of that person's knowledge and belief it includes a true and accurate presentation of the facts.
(3) The Food and Drug Administration will not find a drug product, including any active ingredient, which is identical, related, or similar, as described in § 310.6, to a drug product, including any active ingredient for which an application is or at any time has been effective or deemed approved, or approved under section 505 of the act, to be exempt from part or all of the new drug provisions of the act.
(4) A contention that a drug product is not a new drug for any other reason is required to be supported by submission of the factual records, data, and information that are necessary and appropriate to support the contention.
(5) It is the responsibility of every person who manufactures or distributes a drug product in reliance upon a "grandfather" provision of the act to maintain files that contain the data and information necessary fully to document and support that status.
(f) Separation of functions. Separation of functions commences upon receipt of a request for hearing. The Director of the Center for Drugs and Biologics, Food and Drug Administration, will prepare an analysis of the request and a proposed order ruling on the matter. The analysis and proposed order, the request for hearing, and any proposed order denying a hearing and response under paragraph (g) (2) or (3) of this section will be submitted to the Office of the Commissioner of Food and Drugs for review and decision. When the Center for Drugs and Biologics recommends denial of a hearing on all issues on which a hearing is requested, no representative of the Center will participate or advise in the review and decision by the Commissioner. When the Center for Drugs and Biologics recommends that a hearing be granted on one or more issues on which a hearing is requested, separation of functions terminates as to those issues, and representatives of the Center may participate or advise in the review and decision by the Commissioner on those issues. The Commissioner may modify the text of the issues, but may not deny a hearing on those issues. Separation of functions continues with respect to issues on which the Center for Drugs and Biologics has recommended denial of a hearing. The Commissioner will neither evaluate nor rule on the Center's recommendation on such issues and such issues will not be included in the notice of hearing. Participants in the hearing may make a motion to the presiding officer for the inclusion of any such issue in the hearing. The ruling on such a motion is subject to review in accordance with § 12.35(b). Failure to so move constitutes a waiver of the right to a hearing on such an issue. Separation of functions on all issues resumes upon issuance of a notice of hearing. The Office of the General Counsel, Department of Health and Human Services, will observe the same separation of functions.
(g) Summary judgment. A person who requests a hearing may not rely upon allegations or denials but is required to set forth specific facts showing that there is a genuine and substantial issue of fact that requires a hearing with respect to a particular drug product specified in the request for hearing.
(1) Where a specific notice of opportunity for hearing (as defined in paragraph (a)(1) of this section) is used, the Commissioner will enter summary judgment against a person who requests a hearing, making findings and conclusions, denying a hearing, if it conclusively appears from the face of the data, information, and factual analyses in the request for the hearing that there is no genuine and substantial issue of fact which precludes the refusal to approve the application or the withdrawal of approval of the application; for example, no adequate and well-controlled clinical investigations meeting each of the precise elements of § 314.126 and, for a combination drug product, § 300.50, showing effectiveness have been identified. Any order entering summary judgment is required to set forth the Commissioner's findings and conclusions in detail and is required to specify why each study submitted fails to meet the requirements of the statute and regulations or why the request for hearing does not raise a genuine and substantial issue of fact.
(2) When following a general notice of opportunity for a hearing (as defined in paragraph (a)(1) of this section) the Director of the Center for Drugs and Biologics concludes that summary judgment against a person requesting a hearing should be considered, the Director will serve upon the person requesting a hearing by registered mail a proposed order denying a hearing. This person has 60 days after receipt of the proposed order to respond with sufficient data, information, and analyses to demonstrate that there is a genuine and substantial issue of fact which justifies a hearing.
(3) When following a general or specific notice of opportunity for a hearing a person requesting a hearing submits data or information of a type required by the statute and regulations, and the Director of the Center for Drugs and Biologics concludes that summary judgment against the person should be considered, the Director will serve upon the person by registered mail a proposed order denying a hearing. The person has 60 days after receipt of the proposed order to respond with sufficient data, information, and analyses to demonstrate that there is a genuine and substantial issue of fact which justifies a hearing.
(4) If review of the data, information, and analyses submitted show that the grounds cited in the notice are not valid, for example, that substantial evidence of effectiveness exists, the Commissioner will enter summary judgment for the person requesting the hearing, and rescind the notice of opportunity for hearing.
(5) If the Commissioner grants a hearing, it will begin within 90 days after the expiration of the time for requesting the hearing unless the parties otherwise agree in the case of denial of approval, and as soon as practicable in the case of withdrawal of approval.
(6) The Commissioner will grant a hearing if there exists a genuine and substantial issue of fact or if the Commissioner concludes that a hearing would otherwise be in the public interest.
(7) If the manufacturer or distributor of an identical, related, or similar drug product requests and is granted a hearing, the hearing may consider whether the product is in fact identical, related, or similar to the drug product named in the notice of opportunity for a hearing.
(8) A request for a hearing, and any subsequent grant or denial of a hearing, applies only to the drug products named in such documents.
(h) FDA will issue a notice withdrawing approval and declaring all products unlawful for drug products subject to a notice of opportunity for a hearing, including any identical, related, or similar drug product under § 310.6, for which an opportunity for a hearing is waived or for which a hearing is denied. The Commissioner may defer or stay the action pending a ruling on any related request for a hearing or pending any related hearing or other administrative or judicial proceeding.
§ 314.201 Procedure for hearings.
Parts 10 through 16 apply to hearings relating to new drugs under section 505 (d) and (e) of the act.
(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.
§ 314.300 Procedure for the issuance, amendment, or repeal of regulations.
(a) The procedures in Part 10 apply to the issuance, amendment, or repeal of regulations under section 507 of the act.
(b) (1) The Commissioner of Food and Drugs, on his or her own initiative or on the application or request of any interested person, may publish in the Federal Register a notice of proposed rulemaking and order to issue, amend, or repeal any regulation contemplated by section 507 of the act.
The notice and order may be general (that is, simply summarizing in a general way the information resulting in the notice and order) 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 and order).
(2) The Food and Drug Administration will give interested persons an opportunity to submit written comments and to request an informal conference on the proposal, unless the notice and opportunity for comment and informal conference have already been provided in connection with the announcement of the reports of the National Academy of Sciences/National Research Council, Drug Efficacy Study Group, to persons who will be adversely affected, or as provided in § § 10.40(e) and 12.20(c)(2). A person is required to request an informal conference within 30 days of the notice of proposed rulemaking unless otherwise specified in the notice. If an informal conference is requested and granted, those persons participating in the conference may submit comments, within 30 days of the conference, unless otherwise specified in the proposal.
(3) It is the responsibility of every manufacturer and distributor of an antibiotic drug product to review every proposal published in the Federal Register to determine whether it covers any drug product that person manufactures or distributes.
(4) After considering the written comments, the results of any conference, and the data available, the Commissioner will publish an order in the Federal Register acting on the proposal, with an opportunity for any person who will be adversely affected to file objections, to request a hearing, and to show reasonable grounds for the hearing. Any person who wishes to participate in a hearing, shall file with the Dockets Management Branch (HFA-305), Food and Drug Administration, Rm. 4-62, 5600 Fishers Lane, Rockville, MD 20857, (i) within 30 days after the date of the publication of the order a written notice of participation and request for a hearing and (ii) within 60 days after the date of publication of the order, unless a different period of time is specified in the order, the studies on which the person relies to justify a hearing as specified in paragraph (b)(6) of this section. The person may incorporate by reference the raw data underlying a study if the data were previously submitted to FDA as part of an application or other report.
(5) FDA will not consider data or analysis submitted after 60 days in determining whether a hearing is warranted unless they are derived from well-controlled studies begun before the date of the order and the results of the studies were not available within 60 days after the date of publication of the order. Nevertheless, FDA may consider other studies on the basis of a showing by the person requesting a hearing of inadvertent omission and hardship. The person requesting a hearing shall list in the request for hearing all studies in progress, the results of which the person intends later to submit in support of the request for hearing. The person shall submit under paragraph (b)(4)(ii) of this section a copy of the complete protocol, a list of the participating investigators, and a brief status report of the studies.
(6) The person requesting a hearing is required to submit as required under § 314.200(c)(1)(ii) the studies (including all protocols and underlying raw data) on which the person relies to justify a hearing with respect to the drug product. Except, a person who requests a hearing on a proposal is not required to submit additional studies and analyses if the studies upon which the person relies have been submitted in an application and in the format and containing the summaries required under § 314.50.
(i) If the grounds for DFA proposed action concern the effectiveness of the drug, each request for hearing is required to be supported only by adequate and well-controlled clinical studies meeting all of the precise requirements of § 314.126 and, for combination drug products, § 300.50, or by other studies not meeting those requirements for which a waiver has been previously granted by FDA under § 314.126. Each person requesting a hearing shall submit all adequate and well-controlled clinical studies on the drug product, any unfavorable analyses, views, or judgements with respect to the studies. No other data, information, or studies may be submitted.
(ii) The submission is required to include a factual analyses of all the studies submitted. If the grounds for FDA proposed action concern the effectiveness of the drug, the analysis is required to specify how each study accords, on a point-by-point basis, with each criterion required for an adequate well-controlled clinical investigation established under § 314.126 and, if the product is a combination drug product, with each of the requirements for a combination drug established in § 300.50, or the study is required to be accompanied by an appropriate waiver previously granted by FDA. If a study concerns a drug entity or dosage form or condition of use or mode of administration other than the one in question, that fact is required to be clearly stated. Any study conducted on the final marketed form of the drug product is required to be clearly identified.
(iii) Each person requesting a hearing shall submit an analysis of the data upon which the person relies, except that the required information relating either to safety or to effectiveness may be omitted if the notice of opportunity for hearing does not raise any issue with respect to that aspect of the drug; information on compliance with § 300.50 may be omitted if the drug product is not a combination drug product. FDA can most efficiently consider submissions made in the following format.
a. Controlled studies. b. Partially controlled or uncontrolled studies.
d. Pertinent marketing experiences that may influence a determination about the safety of each individual active component.
1. Controlled studies with an analysis showing clearly how each study satisfies on a point-by-point basis, each of the criteria required by § 314.126.
2. An analysis showing clearly how each requirement of § 300.50 has been satisfied.
(7) Separation of functions. Separation of functions commences upon receipt of a request for hearing. The Director of the Center for Drugs and Biologics will prepare an analysis of the request and a proposed order ruling on the matter. The analysis and proposed order, the request for hearing, and any proposed order denying a hearing and response under paragraph (b)(8) (ii) or (iii) of this section will be submitted to the Office of the Commissioner for review and decision. When the Center for Drugs and Biologics recommends denial of a hearing on all issues on which a hearing is requested, no representative of the Center will participate or advise in the review and decision by the Commissioner. When the Center for Drugs and Biologics recommends that a hearing be granted on one or more issues on which a hearing is requested, separation of functions terminates as to those issues, and representatives of the Center may participate or advise in the review and decision by the Commissioner on those issues. The Commissioner may modify the text of the issues, but may not deny a hearing on those issues. Separation of functions continues with respect to issues on which the Center for Drugs and Biologics has recommended denial of a hearing. The Commissioner will neither evaluate nor rule on the Center's recommendation on such issues and such issues will not be included in the notice of hearing. Participants in the hearing may make a motion to the presiding officer for the inclusion of any such issue in the hearing. The ruling on such a motion is subject to review in accordance with § 12.35(b). Failure to so move constitutes a waiver of the right to a hearing on such an issue. Separation of functions on all issues resumes upon issuance of a notice of hearing. The Office of the General Counsel, Department of Health and Human Services, will observe the same separation of functions.
(8) Summary judgment. A person who requests a hearing may not rely upon allegations or denials but is required to set forth specific facts showing that there is a genuine and substantial issue of fact that requires a hearing with respect to a particular drug product specified in the request for hearing.
(i) Where a specific notice of opportunity for hearing (as defined in paragraph (b)(1) of this section) is used, the Commissioner will enter summary judgment against a person who requests a hearing, making findings and conclusions, denying a hearing, if it conclusively appears from the face of the data, information, and factual analyses in the request for the hearing that there is no genuine and substantial issue of fact which precludes the refusal to approve the application or the withdrawal of approval of the application; for example, no adequate and well-controlled clinical investigations meeting each of the precise elements of § 314.126 and, for a combination drug product, § 300.50, showing effectiveness have been identified. Any order entering summary judgment is required to set forth the Commissioner's findings and conclusions in detail and is required to specify why each study submitted fails to meet the requirements of the statute and regulations or why the request for hearing does not raise a genuine and substantial issue of fact.
(ii) When following a general notice of opportunity for a hearing (as defined in paragraph (b)(1) of this section) the Director of the Center for Drugs and Biologics concludes that summary judgment against a person requesting a hearing should be considered, the Director will serve upon the person requesting a hearing by registered mail a proposed order denying a hearing. This person has 60 days after receipt of the proposed order to respond with sufficient data, information, and analyses to demonstrate that there is a genuine and substantial issue of fact which justifies a hearing.
(iii) When following a general or specific notice of opportunity for a hearing a person requesting a hearing submits data or information of a type required by the statute and regulations, and the Director of the Center for Drugs and Biologics concludes that summary judgment against the person should be considered, the Director will serve upon the person by registered mail a proposed order denying a hearing. The person has 60 days after receipt of the proposed order to respond with sufficient data, information, and analyses to demonstrate that there is a genuine and substantial issue of fact which justifies a hearing.
(iv) If review of the data, information, and analyses submitted show that the basis for the order is not valid, for example, that substantial evidence of effectiveness exists, the Commissioner will enter summary judgment for the person requesting the hearing, and revoke the order. If a hearing is not requested, the order will become effective as published.
(v) If the Commissioner grants a hearing, it will be conducted under Part 12.
(vi) The Commissioner will grant a hearing if there exists a genuine and substantial issue of fact or if the Commissioner concludes that a hearing would otherwise be in the public interest.
(9) The repeal of any regulation constitutes a revocation of all outstanding certificates based upon such regulation. However, the Commissioner may, in his or her discretion, defer or stay such action pending a ruling on any related request for a hearing or pending any related hearing or other administrative or judicial proceeding.
(c) Whenever any interested person submits an application or request under section 507 of the act and Part 314 and FDA sends the person an approvable letter under § 314.110 or a not approvable letter under § 314.120, the person may file a petition proposing the issuance, amendment, or repeal of the regulation under the provisions of section 507(f) of the act and Part 10. The Commissioner shall cause the regulations proposed in the petition to be published in the Federal Register within 60 days of the receipt of an acceptable petition and further proceedings shall be in accord with the provisions of sections 507(f) and 701 (f) and (g) of the act and Part 10.
(d) (1) FDA will no promulgate a regulation providing for the certification of any batch of any drug composed wholly or in part of any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any other antibiotic drug, or any derivative thereof, intended for human use and no existing regulation will be continued in effect unless it is established by substantial evidence that the drug will have such characteristics of identity, strength, quality, and purity necessary to adequately ensure safety and efficacy of use. "Substantial evidence" has been defined by Congress to mean "evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions prescribed, recommended, or suggested in the labeling or proposed labeling thereof." This definition is made applicable to a number of antibiotic drugs by section 507(h) of the act and it is the test of efficacy that FDA will apply in promulgating, amending, or repealing regulations for all antibiotics under section 507(a) of the act as well.
(2) The scientific essentials of an adequate and well-controlled clinical investigation are described in § 314.126.
§ 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.
(iv) It is not sold or offered for sale in the United States.
§ 314.420 Drug master files.
(5) Preclinical or clinical data.
(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 three 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 three 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 authorized to reference the file, is determined under Part 20 and § 314.430.
§ 314.430 Availability for public disclosure of data and information in an application.
(a) The Food and Drug Administration will determine the public availability of any part of an application under this section and Part 20. For purposes of this section, the application includes all data and information submitted with or incorporated by reference in the application, including investigational new drug applications, drug master files under § 314.420, supplements submitted under § 314.70, reports under § 314.80, 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 before an approvable letter is sent to the applicant under § 314.110, unless the existence of the application has been previously publicly disclosed or acknowledged. The Center for Drugs and Biologics will maintain and make available for public disclosure a list of applications for which the agency has sent an approvable letter to the applicant.
(c) If the existence of an unapproved application has not been publicly disclosed or acknowledged, no data or information in the application is available for public disclosure.
(d) If the existence of an 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 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 issue at an open session of an FDA advisory committee.
(e) After FDA sends an approval letter to the applicant, the following data and information in the application are immediately available for public disclosure, unless the applicant shows that extraordinary circumstances exist. A list of approved applications is publicly available from the Government Printing Office, Washington, DC 20402. The list is updated monthly.
(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.
(a) Before approval of the application, the applicant may prepare a draft SBA which the Center for Drugs and Biologics will review and may revise. The draft may be submitted with the application or as an amendment.
(b) The Center for Drugs and Biologics 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.
(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.
(8) All records showing the testing of an action on a particular lot of a certifiable antibiotic by FDA.
(5) For applications submitted under section 505(b) of the act, the effective date of the approval of the first application submitted under section 505(j) of the act which refers to such drug, or the date on which the approval of an application under section 505(j) which refers to such drug could be made effective if such an application had been submitted.
(6) For applications submitted under sections 505(j), 506, and 507 of the act, when FDA sends an approval letter to the applicant.
(h) The compilations of information specified in § 20.117 are available for public disclosure.
§ 314.440 Addresses for applications.
(1) An application under § 314.50 submitted for filing should be directed to the Document and Records Section (HFN-106). Applicants may obtain folders for binding applications from that office. After FDA has filed the application, the agency will inform the applicant which one of the divisions in the Office of New Drug Evaluation 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) An abbreviated application under § 314.55, and amendments, supplements, resubmissions, and other correspondence about an abbreviated application should be directed to the Division of Generic Drugs (HFN-230). Applicants may obtain folders for binding abbreviated applications from that office.
(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 Division of Regulatory Affairs (HFN-360).
(b) Applicants shall send applications and other correspondence relating to matters covered by this part for the drug products listed below to the Office of Biologics Research and Review (HFN-825), Center for Drugs and Biologics, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20205, except applicants shall send a request for an opportunity for a hearing under § 314.110 or § 314.120 on the question of whether these are grounds for denying approval of an application to the Director, Office of Biologics Research and Review (HFN-800), at the same address.
(1) Ingredients packaged together with containers intended for the collection, processing, or storage of blood and blood components.
(3) Plasma volume expanders and hydroxyethyl starch for leukapheresis.
(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 Drugs and Biologics 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 Office of Consumer and Professional Affairs (HFN-10), Center for Drugs and Biologics, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
§ 330.10 Procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded, and for establishing monographs.
(c) Information and data submitted under this section shall include, with respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
§ 430.10 Certification or release of antibiotic drugs affected by the drug amendments of 1962.
(a) Before the 1962 amendments to it, the Federal Food, Drug, and Cosmetic Act only permitted the Food and Drug Administration to provide for the certification of batches of antibiotic drugs containing penicillin, streptomycin, chlortetracycline, chloramphenicol, or bacitracin, or any derivative of them. FDA certified those drugs under regulations promulgated on the basis of scientific proof of the drugs' safety and effectiveness. Most drugs containing an antibiotic other than one of those listed were subject to the new drug provisions of the act, which required that an applicant show that the drug was safe and obtain FDA approval of a new drug application before marketing it. An affirmative showing of effectiveness was not then required to obtain approval. Some antibiotic drugs that were not subject to certification, however, were also not subject to the new drug provisions of the act under informal FDA opinions that the drug was "not a new drug" or "no longer a new drug." FDA revoked those opinions under § 310.100 of this chapter.
(b) The 1962 amendments amended section 507 of the act to require the certification, release without certification, or exemption from certification, of all antibiotic drugs on the basis of scientific proof of safety and effectiveness. The amendments provided that FDA implement them for antibiotic drugs that were marketed on April 30, 1963 and were not subject to the certification provisions on that date. FDA is implementing the amendments with respect to antibiotic drugs formerly subject to the new drug provisions of the act through its Drug Efficacy Study Implementation (DESI) program under which the agency is evaluating those antibiotic drugs for efficacy. Until FDA completes that evaluation it will permit continued marketing of those antibiotic drugs under paragraph (c) of this section. The agency is also implementing the 1962 amendments with respect to antibiotic drugs formerly not subject to either the certification or new drug provisions of the act and the agency is evaluating those antibiotic drugs for both safety and efficacy. Until FDA completes that evaluation, it will permit continued marketing of those antibiotic drugs under paragraph (d) of this section.
(c) Unless exempted from certification, FDA will certify or release antibiotic drugs which on April 30, 1963 were the subject of an approved new drug application under section 505 of the act, under regulations providing for certification of the drugs. Although the initial regulation for each of these drugs established under section 507(h) of the act was not conditioned upon an affirmative finding of the effectiveness of the drug, FDA is proceeding under its DESI program to amend or repeal those regulations to provide for certification of those drugs only if they had been shown to be both safe and effective.
(d) Unless exempted from certification, FDA will release without certification an antibiotic drug that was marketed on April 30, 1963, but not subject to certification, and not subject to an approved new drug application on that date, unless FDA has made a determination that the drug has not been shown to be safe or lacks substantial evidence of effectiveness under the DESI program. FDA is proceeding under its DESI program to establish regulations under section 507 to provide for certification of those drugs only if they have been shown to be safe and effective. § 430.20 [Removed] b. By removing § 430.20 Procedure for the issuance, amendment, or repeal of regulations.
a. In § 431.1 Requests for certification, check tests and assays, and working standards; information and samples required by removing and reserving paragraph (b).
b. By removing § 431.16 Changes in facilities or controls; changes in mailing or promotional pieces.
§ 431.17 Request to provide for certification of an antibiotic drug.
A request under section 507 of the Federal Food, Drug, and Cosmetic Act to provide for certification of an antibiotic drug is required to comply with the procedures and meet the requirements applicable to the submission to the Food and Drug Administration and review by the agency of applications and abbreviated applications, and amendments and supplements to them, under Part 314 of this chapter.
d. In § 431.50 Forms for certification or exemption of antibiotic drugs by removing the entries for Form 5 and Form 6.
e. By removing § 431.60 Records and reports concerning experience with antibiotic drugs for human use for which a certificate or release has been issued.
f. In § 431.70 Confidentiality of data and information in an investigational new drug notice for an antibiotic drug, paragraphs (b) and (c) are amended by changing the references "§ 431.71" to "§ 314.430 of this chapter".
g. By removing § 431.71 Confidentiality of data and information in an antibiotic drug file.
12. Part 433 is amended by removing § 433.25 Antibiotic drugs intended for export.
a. In § 510.3 Definitions and interpretations in paragraph (1) by removing the words "and § 310.9 of this chapter".
§ 511.1 New animal drugs for investigational use exempt from section 512 (a) of the act.
(ii) All labeling and other pertinent information to be supplied to the investigators. When such pertinent information includes nonclinical laboratory studies, the information shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(iii) Will respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
§ 514.8 Supplemental new animal drug applications.
(l) A supplemental application that contains nonclinical laboratory studies shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
§ 514.15 Untrue statements in applications.
(c) Any nonclinical laboratory study contained in the application was not conducted in compliance with the good laboratory practice regulations as set forth in Part 58 of this chapter, and the application fails to include a brief statement of the reason for the noncompliance.
§ 514.110 Reasons for refusing to file applications.
(8) It fails to include, with respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reasons for the noncompliance.
§ 514.111 Refusal to approve an application.
(11) Any 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 as set forth 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.
§ 514.115 Withdrawal of approval of applications.
(4) That any 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 as set forth 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.
(vi) If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(k) If nonclinical laboratory studies are involved, petitions filed with the Commissioner under section 409(b) of the act shall include, with respect to each study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
§ 571.6 Amendment of petition.
* * * If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each such study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason or the noncompliance.
§ 601.2 Applications for establishment and product licenses; procedures for filing.
§ 812.27 Report of prior investigations.
(3) If information on nonclinical laboratory studies is provided, a statement that all such studies have been conducted in compliance with applicable requirements in the good laboratory practice regulations in Part 58, or if any such study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance. Failure or inability to comply with this requirement does not justify failure to provide information on a relevant nonclinical test study.
§ 1003.31 Granting the exemption.
(b) Such views and evidence shall be confined to matters relevant to whether the defect in the product or its failure to comply with an applicable Federal standard is such as to create a significant risk of injury, including genetic injury, to any person and shall be presented in writing unless the Secretary determines that an oral presentation is desirable. Where such evidence includes nonclinical laboratory studies, the data submitted shall include, with respect to each such study, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance. When such evidence includes clinical investigations involving human subjects, the data submitted shall include, with respect to each clinical investigation either a statement that each investigation was conducted in compliance with the requirements set forth in Part 56 of this chapter, or a statement that the investigation is not subject to such requirements in accordance with § 56.104 or § 56.105, and a statement that each investigation was conducted in compliance with the requirements set forth in Part 50 of this chapter.
(ix) With respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
§ 1010.5 Exemptions for products intended for United States Government use.
(13) With respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the requirements set forth in Part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.

References: § 310
 § 310
 § 314
 § 314
 § 300
 § 314
 § 314
 § 300
 § 300
 § 314
 § 314
 § 300
 § 300
 § 314
 § 314
 § 314
 § 314
 § 310
 § 310
 § 314
 § 310
 § 12
 § 314
 § 300
 § 310

§ 314
 § 314
 § 310

§ 314
 § 10
 § 314
 § 314
 § 314
 § 300
 § 314
 § 314
 § 300
 § 300
 § 314
 § 300
 § 12
 § 314
 § 300
 § 314
 § 314
 § 314

§ 314
 § 201

§ 314
 § 10
 § 314

§ 314
 § 314
 § 314
 § 314
 § 314
 § 20
 § 20
 § 20
 § 20

§ 314
 § 314
 § 314
 § 314
 § 314
 § 314
 § 314
 § 10

§ 330

§ 430
 § 310
 § 430
 § 430
 § 431
 § 431

§ 431
 § 431
 § 431
 § 431
 § 431
 § 433
 § 510
 § 310

§ 511

§ 514

§ 514

§ 514

§ 514

§ 514

§ 571

§ 601

§ 812

§ 1003
 § 56
 § 56

§ 1010