(a) Unless the requester justifies an omission in accordance with paragraph (c) of this section, a De Novo request must include:

(1) Table of contents. A table of contents that specifies the volume (if the De Novo request contains more than one volume) and page number for each item.

(2) Administrative information. The name, address, phone, and email address of the requester and U.S. representative, if applicable. The establishment registration number, if applicable, of the owner or operator submitting the De Novo request.

(3) Regulatory history. Identify any prior submissions to FDA for the device, including, but not limited to, any premarket notifications (510(k)s) submitted under part 807 of this chapter; applications for premarket approval (PMAs) submitted under part 814 of this chapter; applications for humanitarian device exemption (HDE) submitted under part 814 of this chapter; applications for investigational device exemption (IDEs) submitted under part 812 of this chapter; requests for designation (RFD) under § 3.7 of this chapter; requests for information under section 513(g) of the Federal Food, Drug, and Cosmetic Act; applications for emergency use authorization (EUA) under section 564 of the Federal Food, Drug, and Cosmetic Act; pre-submissions, or previously submitted De Novo requests; or state that there have been no prior submissions.

(4) Device name. The generic name of the device as well as any proprietary name or trade name.

(5) Indications for use. A general description of the disease or condition the device is intended to diagnose, treat, prevent, cure or mitigate, or affect the structure or function of the body, including a description of the patient population for which the device is intended. The indications for use include all the labeled patient uses of the device, including if it is prescription or over-the-counter.

(6) Device description. A complete description of:

(i) The device, including, where applicable, pictorial representations, device specifications, and engineering drawings;

(ii) Each of the functional components or ingredients of the device, if the device consists of more than one physical component or ingredient;

(iii) The properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or condition and/or the effect of the device on the structure or function of the body;

(iv) The principles of operation of the device; and

(v) The relevant FDA assigned reference number(s) for any medical devices (such as accessories or components) that are intended to be used with the device and that are already legally marketed.

(7) Alternative practices and procedures. A description of existing alternative practices or procedures that are used in diagnosing, treating, preventing, curing, or mitigating the disease or condition for which the device is intended or which similarly affect the structure or function of the body and that are known or should reasonably be known to the requester.

(8) Classification summary. (i) For devices not the subject of a previous submission under section 510(k) of the Federal Food, Drug, and Cosmetic Act, a complete description of:

(A) The searches used to establish that no legally marketed device of the same type exists.

(B) A list of classification regulations, PMAs, HDEs, premarket notifications (510(k)s), EUAs, and/or product codes regarding devices that are potentially similar to the subject device.

(C) A rationale explaining how the device that is the subject of the De Novo request is different from the devices covered by the classification regulations, PMAs, HDEs, 510(k)s, EUAs, and/or product codes identified in paragraph (a)(8)(i)(B) of this section.

(ii) For devices which were the subject of a previous submission under section 510(k) of the Federal Food, Drug, and Cosmetic Act that were determined not substantially equivalent (NSE), the relevant 510(k) number, along with a summary of the search performed to confirm the device has not been classified or reclassified since the date the NSE order was issued by FDA pursuant to § 807.100(a) of this chapter.

(9) Summary of risks and mitigations. A summary of probable risks to health associated with use of the device that are known or should reasonably be known to the requester and the proposed mitigations, including general controls and, if the classification recommendation from paragraph (a)(11) of this section is class II, special controls for each risk. For each mitigation measure that involves specific performance testing or labeling, the De Novo request must provide a reference to the associated section or pages for the supporting information in the De Novo request.

(10) Proposed special controls. If the classification recommendation from paragraph (a)(11) of this section is class II, then the summary must include an initial draft proposal for applicable special controls and a description of how those special controls provide reasonable assurance of safety and effectiveness.

(11) Classification recommendation. The recommended class (I or II) must be identified and must be supported by a description of why general controls, or general and special controls, are adequate to provide reasonable assurance of safety and effectiveness.

(12) Standards. Reference to any published voluntary consensus standards that are relevant to any aspect of the safety or effectiveness of the device and that are known or should reasonably be known to the requester. Such standards include voluntary consensus standards whether recognized or not yet recognized under section 514(c) of the Federal Food, Drug, and Cosmetic Act. Provide adequate information to demonstrate how the device meets, or justify any deviation from, the referenced standard.

(13) Summary of studies. An abstract of any information or report described in the De Novo request under paragraph (a)(16)(ii) of this section and a summary of the results of technical data submitted under paragraph (a)(15) of this section. Each such study summary must include a description of the objective of the study, a description of the experimental design of the study, a brief description of how the data were collected and analyzed, and a brief description of the results, whether positive, negative, or inconclusive. This section must also include the following:

(i) A summary of each nonclinical study submitted in the De Novo request;

(ii) A summary of each clinical investigation involving human subjects submitted in the De Novo request, including a discussion of investigation design, subject selection and exclusion criteria, investigation population, investigation period, safety and effectiveness data, adverse reactions and complications, subject discontinuation, subject complaints, device failures (including unexpected software events, if applicable) and replacements, results of statistical analyses of the clinical investigations, contraindications and precautions for use of the device, and other information from the clinical investigations as appropriate. Any investigation conducted under an investigational device exemption (IDE) under part 812 of this chapter must be identified as such.

(14) Benefit and risk considerations. A discussion demonstrating that:

(i) The data and information in the De Novo request constitute valid scientific evidence within the meaning of § 860.7(c) and

(ii) Pursuant to § 860.7, when subject to general controls, or general and special controls, the probable benefit to health from use of the device outweighs any probable injury or illness from such use.

(15) Technical sections. The following technical sections, which must contain data and information in sufficient detail to permit FDA to determine whether to grant or decline the De Novo request:

(i) A section containing the results of the nonclinical studies of the device, including, as appropriate, microbiological, toxicological, immunological, biocompatibility, stress, wear, shelf life, electrical safety, electromagnetic compatibility, and other laboratory or animal tests. Information on nonclinical studies must include protocols and complete test reports for each study. For those nonclinical studies subject to part 58 of this chapter, this section must include a statement that each such study was conducted in compliance with such regulations, or, if the study was not conducted in compliance with part 58 of this chapter, a brief statement of the reason for the noncompliance.

(ii) For all devices that incorporate software, a section containing all relevant software information and testing, including, but not limited to, appropriate device hazard analysis, hardware, and system information.

(iii) A section containing results of each clinical investigation of the device involving human subjects, including clinical protocols, number of investigators and subjects per investigator, investigation design, subject selection and exclusion criteria, investigation population, investigation period, safety and effectiveness data, adverse reactions and complications, subject discontinuation, subject complaints, device failures (including unexpected software events if applicable) and replacements, tabulations of data from all individual subject report forms and copies of such forms for each subject who died during a clinical investigation or who did not complete the investigation, results of statistical analyses of the results of the clinical investigations, contraindications, warnings, precautions, and other limiting statements relevant to the use of the device type, and any other appropriate information from the clinical investigations. Any investigation conducted under an IDE under part 812 of this chapter must be identified as such. Information on clinical investigations involving human subjects must include the following:

(A) For clinical investigations conducted in the United States, a statement with respect to each investigation that it either was conducted in compliance with the institutional review board regulations in part 56 of this chapter, or was not subject to the regulations under § 56.104 or § 56.105 of this chapter, and that it was conducted in compliance with the informed consent regulations in part 50 of this chapter; or if the investigation was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance. Failure or inability to comply with these requirements does not justify failure to provide information on a relevant clinical investigation.

(B) For clinical investigations conducted in the United States, a statement that each investigation was conducted in compliance with part 812 of this chapter concerning sponsors of clinical investigations and clinical investigators, or if the investigation was not conducted in compliance with those regulations, a brief statement of the reason for the noncompliance. Failure or inability to comply with these requirements does not justify failure to provide information on a relevant clinical investigation.

(C) For clinical investigations conducted outside the United States that are intended to support the De Novo request, the requirements under § 812.28 of this chapter apply. If any such investigation was not conducted in accordance with good clinical practice (GCP) as described in § 812.28(a) of this chapter, include either a waiver request in accordance with § 812.28(c) of this chapter or a brief statement of the reason for not conducting the investigation in accordance with GCP and a description of steps taken to ensure that the data and results are credible and accurate and that the rights, safety, and well-being of subjects have been adequately protected. Failure or inability to comply with these requirements does not justify failure to provide information on a relevant clinical investigation.

(D) A statement that each investigation has been completed per the protocol or a summary of any protocol deviations.

(E) A financial certification or disclosure statement or both as required by part 54 of this chapter.

(F) For a De Novo request that relies primarily on data from a single investigator at one investigation site, a justification showing that these data and other information are sufficient to reasonably demonstrate the safety and effectiveness of the device when subject to general controls or general and special controls, and to ensure that the results from a site are applicable to the intended population.

(G) A discussion of how the investigation data represent clinically significant results, pursuant to § 860.7(e).

(16) Other information. (i) A bibliography of all published reports not submitted under paragraph (a)(15) of this section, whether adverse or supportive, known to or that should reasonably be known to the requester and that concern the safety or effectiveness of the device.

(ii) An identification, discussion, and analysis of any other data, information, or report relevant to an evaluation of the safety and effectiveness of the device known to or that should reasonably be known to the requester from any source, foreign or domestic, including information derived from investigations other than those in the request and from commercial marketing experience.

(iii) Copies of such published reports or unpublished information in the possession of or reasonably obtainable by the requester, if requested by FDA.

(17) Samples. If requested by FDA, one or more samples of the device and its components. If it is impractical to submit a requested sample of the device, the requester must name the location at which FDA may examine and test one or more of the devices.

(18) Labeling and advertisements. Labels, labeling, and advertisements sufficient to describe the device, its intended use, and the directions for its use. Where applicable, photographs or engineering drawings must be supplied.

(19) Other information. Such other information as is necessary to determine whether general controls or general and special controls provide reasonable assurance of safety and effectiveness of the device.

(b) Pertinent information in FDA files specifically referred to by a requester may be incorporated into a De Novo request by reference. Information submitted to FDA by a person other than the requester will not be considered part of a De Novo request unless such reference is authorized in writing by the person who submitted the information.

(c) If the requester believes that certain information required under paragraph (a) of this section to be in a De Novo request is not applicable to the device that is the subject of the De Novo request, and omits any such information from the De Novo request, the requester must submit a statement that specifies the omitted information and justifies the omission. The statement must be submitted as a separate section in the De Novo request and listed in the table of contents. If the justification for the omission is not accepted by FDA, FDA will so notify the requester.

(d) The requester must update the pending De Novo request with new safety and effectiveness information learned about the device from ongoing or completed studies and investigations that may reasonably affect an evaluation of the safety or effectiveness of the device as such information becomes available.