Ordinarily, any such findings would result in a safety-related change in the protocol, informed consent, investigator brochure (excluding routine updates of these documents), or other aspects of the overall conduct of the clinical investigation. Choosing an item from Nomenclature changes to part 312 appear at 69 FR 13717, Mar. Electronic Code of Federal Regulations (e-CFR), CHAPTER IFOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES, PART 312INVESTIGATIONAL NEW DRUG APPLICATION, Subpart BInvestigational New Drug Application (IND). 21 CFR 312.33 for content and format of IND application . A sponsor-investigator who uses, as a research tool, an investigational new drug that is already subject to a manufacturer's IND or marketing application should follow the same general format, but ordinarily may, if authorized by the manufacturer, refer to the manufacturer's IND or marketing application in providing the technical information supporting the proposed clinical investigation. (3) Introductory statement and general investigational plan. Each submission relating to an IND is required to be numbered serially using a single, three-digit serial number. contact the publishing agency. (iv) A summary of information relating to safety and effectiveness in humans obtained from prior clinical studies. Such information is required to include the identification and qualifications of the individuals who evaluated the results of such studies and concluded that it is reasonably safe to begin the proposed investigations and a statement of where the investigations were conducted and where the records are available for inspection. Microsoft Edge, Google Chrome, Mozilla Firefox, or Safari. (f) A brief summary of significant foreign marketing developments with the drug during the past year, such as approval of marketing in any country or withdrawal or suspension from marketing in any country. (b) Information previously submitted. However, if any component in such combination is subject to an approved marketing application or is otherwise lawfully marketed in the United States, the sponsor is not required to submit published material concerning that active drug component unless such material relates directly to the proposed investigational use (including publications relevant to component-component interaction). The total number of subjects and patients included in Phase 1 studies varies with the drug, but is generally in the range of 20 to 80. eCTD Submission: FDA Guidelines & Avoiding Common Mistakes - Allucent 312.33 Annual reports. A sponsor-investigator who uses an investigational drug not subject to a manufacturer's IND or marketing application is ordinarily required to submit all technical information supporting the IND, unless such information may be referenced from the scientific literature. They are performed after preliminary evidence suggesting effectiveness of the drug has been obtained, and are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling. The sponsor must also submit safety information from the clinical study as prescribed by the postmarketing safety reporting requirements (e.g., 310.305, 314.80, and 600.80 of this chapter). (b) Review of safety information. If you would like to comment on the current content, please use the 'Content Feedback' button below for instructions on contacting the issuing agency. Electronic Code of Federal Regulations (eCFR). An adverse event or suspected adverse reaction is considered "unexpected" if it is not listed in the investigator brochure or is not listed at the specificity or severity that has been observed; or, if an investigator brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current application, as amended. 1 CFR 1.1 This is an automated process for A sponsor is not required to submit annual reports to an IND on inactive status. (i) Serious and unexpected suspected adverse reaction. (a) If no subjects are entered into clinical studies for a period of 2 years or more under an IND, or if all investigations under an IND remain on clinical hold for 1 year or more, the IND. For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR). It does not include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, might have caused death. (a) At any time a sponsor may withdraw an effective IND without prejudice. (b ) For each toxicology study that is intended primarily to support the safety of the proposed clinical investigation, a full tabulation of data suitable for detailed review. A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes: (a) Individual study information. The information on this page is current as of Jun 07, 2023. Plans for assessing pediatric safety and effectiveness. As drug development proceeds, the sponsor is required to submit informational amendments, as appropriate, with additional information pertinent to safety. eCFR :: 21 CFR Part 312 -- Investigational New Drug Application IND Annual Reports (21 CFR 312.33) IND Protocol Amendments (21 CFR 312.30) IND Information Amendments (21 CFR 312.31) Significant FDA Communications Must be Reported to NIH Regulatory Binder (Essential Documents) Research 411 Portal Still Need Help? The sponsor must report any findings from epidemiological studies, pooled analysis of multiple studies, or clinical studies (other than those reported under paragraph (c)(1)(i) of this section), whether or not conducted under an IND, and whether or not conducted by the sponsor, that suggest a significant risk in humans exposed to the drug. This action may be taken by FDA either on request of the sponsor or on FDA's own initiative. A brief summary of the status of each study in progress and each study completed during the previous year. No changes found for this content after 1/03/2017. Once an IND is in effect, a sponsor shall amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application. 4, 2002]. (e) Disclaimer. Enhanced content is provided to the user to provide additional context. Sponsors are expected to submit a brief report of the progress of the studies conducted under their IND application annually within 60 days of the anniversary date that the IND went into effect (21 CFR 312.33). (4) A list of subjects who dropped out during the course of the investigation in association with any adverse experience, whether or not thought to be drug related. All submissions with IND. (d ) Labeling. (a) Definitions. FDA Form 1571 - IND Application. A list of all components, which may include reasonable alternatives for inactive compounds, used in the manufacture of the investigational drug product, including both those components intended to appear in the drug product and those which may not appear but which are used in the manufacturing process, and, where applicable, the quantitative composition of the investigational drug product, including any reasonable variations that may be expected during the investigational stage; the name and address of the drug product manufacturer; a brief general description of the manufacturing and packaging procedure as appropriate for the product; the acceptable limits and analytical methods used to assure the identity, strength, quality, and purity of the drug product; and information sufficient to assure the product's stability during the planned clinical studies. The information on this page is current as of Jun 07, 2023. However, if a serious and unexpected adverse event occurs for which there is evidence suggesting a causal relationship between the drug and the event (e.g., death from anaphylaxis), the event must be reported under 312.32(c)(1)(i) as a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint (e.g., all-cause mortality). (7) A summary of any significant manufacturing or microbiological changes made during the past year. (iii) Findings from animal or in vitro testing. Section 312.23 outlines the information needed for a commercially sponsored IND for a new molecular entity. A safety report or other information submitted by a sponsor under this part (and any release by FDA of that report or information) does not necessarily reflect a conclusion by the sponsor or FDA that the report or information constitutes an admission that the drug caused or contributed to an adverse event. However, if a serious and unexpected adverse event occurs for which there is evidence suggesting a causal relationship between the drug and the event (e.g., death from anaphylaxis), the event must be reported under 312.32(c)(1)(i) as a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint (e.g., all-cause mortality). A narrative or tabular summary showing the most frequent and most serious adverse experiences by body system during the past year. 4, 2002], Note: If you need help accessing information in different file formats, see (3) Reporting format or frequency. Investigational New Drug Application Annual Reporting PDF Required Periodic FDA Submissions for IND Sponsors and Sponsor (3) If the sponsor desires FDA to comment on an information amendment, a request for such comment. IND Application Reporting: Annual Reports IND application sponsors are expected to submit brief reports of the progress of the investigations conducted under their respective IND. IND Templates, Education & Useful Links | Clinical Research Resource HUB Phase 1 studies are typically closely monitored and may be conducted in patients or normal volunteer subjects. Each submission relating to an IND is required to be numbered serially using a single, three-digit serial number. The following definitions of terms apply to this section: Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. (c ) The criteria for patient selection and for exclusion of patients and an estimate of the number of patients to be studied. A reference to information submitted previously must identify the file by name, reference number, volume, and page number where the information can be found. [Code of Federal Regulations] [Title 21, Volume 5] [CITE: 21CFR314.81] TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER D - DRUGS. In certain applications, as described below, information on special topics may be needed. Information amendments to the IND should be submitted as necessary but, to the extent feasible, not more than every 30 days. Phase 1 studies of radioactive drugs must include studies which will obtain sufficient data for dosimetry calculations. Title 21 was last amended 6/22/2023. Instructions for Downloading Viewers and Players. 312.38: Withdrawal of an IND. FDA shall provide a written determination 30 days after FDA receives the IND or earlier. CFR 312.31: Information Amendments (IA) (a) "A sponsor shall report in an information amendment essentialinformation on the IND Examples of information requiring IA include:" FDA IND Regulations (cont'd) (a)(1) "New toxicology, chemistry, or other technical information;" CFR 312.33: Annual Reports (AR) Upon receipt of such notification, the sponsor shall have 30 days to respond as to why the IND should continue to remain active. You are using an unsupported browser. IND Application Reporting: Overview | FDA Additional information supporting the proposed investigation, if any, shall be submitted in an information amendment. Guidance for Industry - U.S. Food and Drug Administration We recommend you directly contact the agency associated with the content in question. (ii) Radioactive drugs. (iv) A commitment that an Institutional Review Board (IRB) that complies with the requirements set forth in part 56 will be responsible for the initial and continuing review and approval of each of the studies in the proposed clinical investigation and that the investigator will report to the IRB proposed changes in the research activity in accordance with the requirements of part 56. (c) A description of the general investigational plan for the coming year to replace that submitted 1 year earlier. (4) Investigations of marketed drugs. Reports of overall findings or pooled analyses from published and unpublished in vitro, animal, epidemiological, or clinical studies must be submitted in a narrative format. (vi) The name and title of the person responsible for monitoring the conduct and progress of the clinical investigations. (g ) A description of clinical procedures, laboratory tests, or other measures to be taken to monitor the effects of the drug in human subjects and to minimize risk. The summary is required to include the following information for each study: (1) The title of the study (with any appropriate study identifiers such as protocol number), its purpose, a brief statement identifying the patient population, and a statement as to whether the study is completed. Annual Report 60 days of the anniversary of the IND effective date 21 CFR 312.33 . A reference to information submitted to the agency by a person other than the sponsor is required to contain a written statement that authorizes the reference and that is signed by the person who submitted the information. The Office of the Federal Register publishes documents on behalf of Federal agencies but does not have any authority over their programs. 49 CFR 172.101 Organization and Purpose A sponsor of a clinical study of a drug marketed or approved in the United States that is conducted under an IND is required to submit IND safety reports for suspected adverse reactions that are observed in the clinical study, at domestic or foreign study sites. (e ) Environmental analysis requirements. (Reprints of published articles on such studies may be appended when useful.). Within 14 months after the date on which a drug was designated as an orphan drug and annually thereafter until marketing approval, the sponsor of a designated drug shall submit a brief progress report to the FDA Office of Orphan Products . Annual Summary Reporting Requirements Under the Right to Try Act (d ) A description of the design of the study, including the kind of control group to be used, if any, and a description of methods to be used to minimize bias on the part of subjects, investigators, and analysts. (iii) In the case of a new investigator, the investigator's name, the qualifications to conduct the investigation, reference to the previously submitted protocol, and all additional information about the investigator's study as is required under 312.23(a)(6)(iii)(b ). A sponsor need not admit, and may deny, that the report or information submitted by the sponsor constitutes an admission that the drug caused or contributed to an adverse event. For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR). IND Annual Report Definition | Law Insider An inactive IND is, however, still in effect for purposes of the public disclosure of data and information under 312.130. user convenience only and is not intended to alter agency intent If the due date of the first annual report does not coincide with the date the IRB Continuing Review. 4. . The sponsor may also propose and adopt a different reporting format or frequency if the change is agreed to in advance by the director of the FDA review division that has responsibility for review of the IND. here. (v) A commitment to conduct the investigation in accordance with all other applicable regulatory requirements. (b) Review of safety information. "Published Edition". A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes: (a) Individual study information. Serious adverse event or serious suspected adverse reaction. If required under 312.55, a copy of the investigator's brochure, containing the following information: (i) A brief description of the drug substance and the formulation, including the structural formula, if known. A description of the drug substance, including its physical, chemical, or biological characteristics; the name and address of its manufacturer; the general method of preparation of the drug substance; the acceptable limits and analytical methods used to assure the identity, strength, quality, and purity of the drug substance; and information sufficient to support stability of the drug substance during the toxicological studies and the planned clinical studies. (b ) The change has been approved by the IRB with responsibility for review and approval of the study. Here is some basic information. This section sets forth the provisions under which new protocols may be submitted and changes in previously submitted protocols may be made. (1) The sponsor must promptly investigate all safety information it receives. 7. Examples of information requiring an information amendment include: (1) New toxicology, chemistry, or other technical information; or. A cover sheet for the application containing the following: (i) The name, address, and telephone number of the sponsor, the date of the application, and the name of the investigational new drug. A safety report or other information submitted by a sponsor under this part (and any release by FDA of that report or information) does not necessarily reflect a conclusion by the sponsor or FDA that the report or information constitutes an admission that the drug caused or contributed to an adverse event. Protocol amendments to add a new investigator or to provide additional information about investigators may be grouped and submitted at 30-day intervals. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if the investigator brochure listed only cerebral vascular accidents. (a ) An integrated summary of the toxicological effects of the drug in animals and in vitro. A brief summary of the status of each study in progress and each study completed during the previous . PDF Investigational New Drug (IND): Sponsor and Investigator Responsibilities Subpart B - Investigational New Drug Application (IND). If you have comments or suggestions on how to improve the www.ecfr.gov website or have questions about using www.ecfr.gov, please choose the 'Website Feedback' button below. SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is proposing to replace its current annual reporting requirement for investigational new drug applications (INDs) with a new requirement: the annual FDA development safety update report (FDA DSUR). (e) An IND that remains on inactive status for 5 years or more may be terminated under 312.44. (a) A sponsor shall submit an IND to FDA if the sponsor intends to conduct a clinical investigation with an investigational new drug that is subject to 312.2(a). (d) Number of copies. A brief summary of the status of each study in progress and each study completed during the previous year. A brief summary of the status of each study in progress and each study completed during the previous year. Instructions for Downloading Viewers and Players. Sec. (a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an "Investigational New Drug Application" (IND) including, in the following order: (1) Cover sheet (Form FDA . eCFR :: 21 CFR 316.30 -- Annual reports of holder of orphan-drug CFR - Code of Federal Regulations Title 21 - Food and Drug Administration (4) A list of subjects who dropped out during the course of the investigation in association with any adverse experience, whether or not thought to be drug related. A protocol for a Phase 2 or 3 investigation should be designed in such a way that, if the sponsor anticipates that some deviation from the study design may become necessary as the investigation progresses, alternatives or contingencies to provide for such deviation are built into the protocols at the outset. The sponsor must report an adverse event as a suspected adverse reaction only if there is evidence to suggest a causal relationship between the drug and the adverse event, such as: (A) A single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome); (B) One or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture); (C) An aggregate analysis of specific events observed in a clinical trial (such as known consequences of the underlying disease or condition under investigation or other events that commonly occur in the study population independent of drug therapy) that indicates those events occur more frequently in the drug treatment group than in a concurrent or historical control group.