The amendment to the IDE regulation was published in the Federal Register as a proposed rule on July 15, 1998 and as a final rule on November 23, 1998. Thus, the device, the protocol, the monitoring procedures, labeling, etc. (iii) The methods, facilities, and controls used for the manufacturing, processing, and packing of the investigational drug are inadequate to establish and maintain appropriate standards of identity, strength, quality, and purity as needed for subject safety. 1040 et seq. use, the notification of substantial amendments and the declaration of the end of the trial (CT-1) (2010/C 82/01) Drug Information Association www.diahome.org 20 27 Member States A clinical trial may be conducted only in one Member State or in more than one Member State 15, 1992; 61 FR 51530, Oct. 2, 1996; 63 FR 68678, Dec. 14, 1998; 64 FR 54189, Oct. 5, 1999; 65 FR 34971, June 1, 2000; 74 FR 40942, Aug. 13, 2009]. Instructions for Downloading Viewers and Players. Changes or modifications to the clinical protocol may be reported in a 5-day notice if the changes do not affect: a) the validity of the data or information resulting from the completion of the approved protocol, or the relationship of likely patient risk to benefit relied upon to approve the protocol; b) the scientific soundness of the investigational plan; or c) the rights, safety, or welfare of the human subjects involved in the investigation. (b) Grounds for termination - (1) Phase 1. Certain changes or modifications to a clinical investigation require submission of an IDE supplement and approval by FDA before implementation. The information required in a Notice of IDE Change varies depending upon whether the change is a developmental change in the device or manufacturing process or a change to the clinical protocol. A design modification to the tip of the catheter used during stent placement to reduce the risk of the tip being snagged on the stent strut when it is being withdrawn. PDF Score Premature Termination or Suspension of Clinical Trial (1) End-of-Phase 2 meetings - (i) Purpose. In order for the IDE regulation to reflect the new statutory language and, as required by the new law, FDA modified the IDE regulation. (c) A sponsor may ship an investigational new drug to investigators named in the IND: (1) Thirty days after FDA receives the IND; or. When an ongoing study is placed on clinical hold, no new subjects may be recruited to the study and placed on the investigational drug; patients already in the study should be taken off therapy involving the investigational drug unless specifically permitted by FDA in the interest of patient safety. Adding contraindications, hazards, adverse effects, interfering substances/devices, warnings, or precautions to the labeling, however, may require concomitant changes to the protocol (e.g., modifications to the exclusion criteria) and thus should be submitted as an IDE supplement or within 5 days of implementation, as appropriate for the protocol modification. Study objectives related to future labeling claims for the device may be added if such changes meet the statutory criteria. A notice for a protocol change should include: 1) a description of the change (cross-referenced to the appropriate sections of the original protocol); 2) an assessment supporting the conclusion that the change does not have a significant impact on the study design or planned statistical analysis; and 3) a summary of the information that served as the credible information supporting the sponsors determination that the change does not affect the rights, safety or welfare of the subjects. The Epic Application Teams technical work generally takes about one business day. FDA encourages such meetings to the extent that they . Several of these provisions were specifically aimed at the clinical trial process. Is a summary provided of the credible information supporting the change? If preclinical/animal testing is used to assess the change, documentation should include information to indicate that the appropriate testing was conducted to address safety and performance concerns (for example, to meet a standard that is identified as a device input requirement). [52 FR 8831, Mar. An updated Investigator's Brochure, including all safety information and global status should be submitted annually. Circumstantial events notifications. The review committee (MREC or CCMO) must be notified of the end date as defined in the protocol within 56 days (8 weeks) of the end of the study. Whenever FDA concludes that a deficiency exists in a clinical investigation that may be grounds for the imposition of clinical hold FDA will, unless patients are exposed to immediate and serious risk, attempt to discuss and satisfactorily resolve the matter with the sponsor before issuing the clinical hold order. Below, the sponsors responsibilities in the various types of submissions and FDAs actions on them are discussed. FDA may propose to terminate an IND during Phase 2 or Phase 3 if FDA finds that: (i) Any of the conditions in paragraphs (b)(1)(i) through (b)(1)(xi) of this section apply; or, (ii) The investigational plan or protocol(s) is not reasonable as a bona fide scientific plan to determine whether or not the drug is safe and effective for use; or. (iv) Any other information for discussion at the meeting. 4, 2002]. Minor changes eligible for reporting in an annual report are those that would not affect: a) the validity of the data or information resulting from the completion of the approved protocol, or the relationship of likely patient risk to benefit relied upon to approve the protocol; b) the scientific soundness of the investigational plan; or c) the rights, safety or welfare of the subjects involved in the investigation. (ii) The pertinent criteria in 50.24 of this chapter for such an investigation to begin or continue are not submitted or not satisfied. * The credible information should include all tests required by FDA during the approval process for the original IDE, if relevant to the change. (ii) Changes to clinical protocol. This section describes the procedures under which FDA may terminate an IND. If a sponsor of an IND that has been placed on clinical hold requests in writing that the clinical hold be removed and submits a complete response to the issue(s) identified in the clinical hold order, FDA shall respond in writing to the sponsor within 30-calendar days of receipt of the request and the complete response. A change to the protocol to allow the use of a 6 French or greater guide catheter rather than the 7 French or greater that was identified in the original protocol. If preclinical/animal testing was used to assess the change, is information provided to indicate that the appropriate testing was conducted to address safety or performance concerns (for example, to meet a standard that is identified as a device input requirement)? L. 105-115), which amended the Federal Food, Drug and Cosmetic Act (the act) by adding section 520(g)(6). Notwithstanding paragraphs (a) through (c) of this section, if at any time FDA concludes that continuation of the investigation presents an immediate and substantial danger to the health of individuals, the agency shall immediately, by written notice to the sponsor from the Director of the Center for Drug Evaluation and Research or the Director of the Center for Biologics Evaluation and Research, terminate the IND. As a result of this new provision, the investigational device exemptions (IDE) regulation (21 CFR 812) was amended. Additionally, both industry and CDRH staff have expressed interest in having guidance on the preparation and review of IDE submissions under this regulation. Is there a change to the device design or manufacturing process? U.S. Food and Drug Administration The analysis may determine that this change may impact the devices strength, flexibility and biocompatibility compared to the unmodified device, but not lead to the identification of any new risks. Requests for such meetings shall be directed to the director of the division in FDA's Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research which is responsible for review of the IND. (2) Changes effected for emergency use.1 The requirements of paragraph (a)(1) of this section regarding FDA approval of a supplement do not apply in the case of a deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. Reviewer: ______________________________. The sponsor would then proceed to evaluate the above risks using credible information. Instructions for Downloading Viewers and Players. Such deviations are addressed in the guidance document entitled, "Guidance for the Emergency Use of Unapproved Medical Devices" (50 FR 42866, October 22, 1985) as well as in the guidance entitled, "IDE Policies and Procedures." Is the change to the basic principles of operation or otherwise a significant change (that is, introduces new risks)? April 28, 2021 Statement From: Janet Woodcock, M.D. FDA will, in general, only initiate an action under this section after first attempting to resolve differences informally or, when appropriate, through the clinical hold procedures described in 312.42. Language Assistance Available: Espaol | | Ting Vit | | Tagalog | | | Kreyl Ayisyen | Franais | Polski | Portugus | Italiano | Deutsch | | | English, The information on this page is current as of. While the statute and the regulation clearly state that it is the sponsors responsibility to determine if a device, manufacturing, or protocol change meet the statutory criteria for implementation without prior agency approval, under 812.35(a)(3)(v), FDA reserved the right to question the sponsors determination. An investigation may only resume after FDA (usually the Division Director, or the Director's designee, with responsibility for review of the IND) has notified the sponsor that the investigation may proceed. If the risk analysis identifies a new type of risk, then prior approval would be needed. Approvals Needed for Research. On April 28, 2021, the US Food and Drug Administration (FDA) issued the first-ever Notice of Noncompliance to a drug maker that did not comply with its legal reporting obligations for clinical trials. This section describes the procedures under which FDA may terminate an IND. (Credible information may include a summary of the information generated under the design control procedures of Sec. PDF EudraCT & EU CTR Frequently asked questions The FDA approved FOTIVDA based on evidence from one clinical trial of 350 adult patients with advanced kidney cancer (renal cell carcinoma or RCC). (2) On such notification, the sponsor may provide a written explanation or correction or may request a conference with FDA to provide the requested explanation or correction. To close out aclinical trial altogether, call emailITHELPDESK@mountsinai.organd provide them with the following information: Short Study Name (to uniquely identify protocol): __________________, Brief Description (Intervention, etc. This guidance document incorporates the discussion from the preambles of the proposed and final rules amending the IDE regulation to implement new section 520(g)(6) of the act. For the remaining types of device and manufacturing changes listed above, the changes can range from minor to significant, depending upon the particular device, the type of modification, and the extent of the modification. (ix) The sponsor fails to comply with any other applicable requirement of this part, part 50, or part 56. If necessary, sponsors may request a meeting with the appropriate reviewing officials and management representatives in order to seek a resolution. (b) "End-of-Phase 2" meetings and meetings held before submission of a marketing application. (d) An investigator may not administer an investigational new drug to human subjects until the IND goes into effect under paragraph (b) of this section. Change in the method of estimation. Notifications allow sponsors to notify MSC(s) of relevant events during a clinical trial life cycle. If an IND is terminated, the sponsor shall end all clinical investigations. Study teams are also required to report study termination/suspension to ISMMS PHHS. Under 812.35(a) of the IDE regulation, it is the sponsor's responsibility to consider the effect that any change made to the investigational plan may have on the clinical investigation and the resulting data. 312.44 Termination. Sec. PDF CTTM13 - FAQs - European Medicines Agency In general, IRB approval should not be required, as the changes presumably do not affect the rights, safety, or welfare of the subjects. U.S. Department Of Health and Human Services Comments may not be acted upon by the agency until the document is next revised or updated. A letter from the sponsor is required stating that all obligations have been met and no money is due back to them. Such deviation shall be reported to FDA within 5 working days after the sponsor learns of it (see 812.150(a)(4)). Notices should be clearly identified as a "Notice of IDE Change" and be submitted in triplicate, referencing the IDE number, to the above address. (a) FDA may at any time during the course of the investigation communicate with the sponsor orally or in writing about deficiencies in the IND or about FDA's need for more data or information. Such determinations will be made by the individuals authorized to approve IDEs. If the clinical study has ended earlier, the timeframe mentioned above is reduced to 15 days, and the reasons should be clearly explained in the notification. (2) Phase 2 or 3. (3) If the sponsor responds but FDA does not accept the explanation or correction submitted, FDA shall inform the sponsor in writing of the reason for the nonacceptance and provide the sponsor with an opportunity for a regulatory hearing before FDA under part 16 on the question of whether the IND should be terminated. Any of these types of information may be used to support a design and/or manufacturing change, meeting the criteria discussed above, in a 5-day notice. 4, 2002]. _____________________________________________________________ If a letter from the sponsor cannot be obtained, please download and fill out the Closeout Letter Template and have it signed by the chairperson of the department. There may be cases, however, in which, depending upon the type of protocol change being implemented, IRB approval may be required under 56.110. The sponsor is responsible for initially determining if the change meets the statutory criteria. All written comments should be identified with this document's docket number: FDA-2020-D-0957. A marker band was added to an investigational device to enhance visualization during fluoroscopy. (2) On earlier notification by FDA that the clinical investigations in the IND may begin. These include the Agreement/Determination meetings provisions and the least burdensome provisions (sections 201 and 205 of FDAMA, respectively). Following the flowchart, FDA recommends that the sponsor use the data generated by design control procedures or other credible information to help determine whether the change has a significant affect on the device design. C. Expectations of European Union (EU) competent authorities on the use of electronic trial master files. (1) Changes requiring prior approval. According to the IDE Modification regulation ( 812.35(a)(3)(iii)(B)), credible information to support changes to the clinical protocol is defined as the sponsors documentation supporting the conclusion that a change does not have a significant impact on the study design or planned statistical analysis, and that the change does not affect the rights, safety, or welfare of the subjects. NOTE: Health Canada may suspend or cancel a trial in instances such as, but not limited to: A sponsor has contravened the Act or Regulations relating to the drug; Any information submitted in respect of the drug or clinical trial is false or misleading