(a) The purpose of this part is to establish an efficient, transparent, and thorough process to facilitate De Novo classification into class I or class II for devices for which there is no legally marketed device on which to base a review of substantial equivalence and which meet the definition of class I or class II as described in section 513(a)(1) of the Federal Food, Drug, and Cosmetic Act and § 860.3.

(b) De Novo requests can be submitted for a single device type:

(1) After receiving a not substantially equivalent determination in response to a premarket notification (510(k)), or

(2) If a person determines there is no legally marketed device upon which to base a determination of substantial equivalence.

(a) Each De Novo request or information related to a De Novo request pursuant to this part must be formatted in accordance with this section. Each De Novo request must be provided as a single version in electronic format. These materials must:

(1)(i) For devices regulated by the Center for Devices and Radiological Health, be sent to the current address displayed on the website https://www.fda.gov/cdrhsubmissionaddress.

(ii) For devices regulated by the Center for Biologics Evaluation and Research, be sent to the current address displayed on the website https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/regulatory-submissions-electronic-and-paper.

(2) Be signed by the requester or an authorized representative.

(3) Be designated “De Novo Request” in the cover letter.

(4) Have all content used to support the request written in, or translated into, English.

(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.

(a) The acceptance of a De Novo request means that FDA has made a threshold determination that the De Novo request contains the information necessary to permit a substantive review. Within 15 days after a De Novo request is received by FDA, FDA will notify the requester whether the De Novo request has been accepted.

(b) If FDA does not find that any of the reasons in paragraph (c)(1) of this section for refusing to accept the De Novo request apply or FDA fails to complete the acceptance review within 15 days, FDA will accept the De Novo request for review and will notify the requester. The notice will include the De Novo request reference number and the date FDA accepted the De Novo request. The date of acceptance is the date that an accepted De Novo request was received by FDA.

(c)(1) FDA may refuse to accept a De Novo request if any of the following applies:

(i) The requester has an open or pending premarket submission or reclassification petition for the device;

(ii) The De Novo request is incomplete because it does not on its face contain all the information required under section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act or does not contain each of the items required under this part, or a justification for omission of any item;

(iii) The De Novo request is not formatted as required under § 860.210;

(iv) The De Novo request is for multiple devices and those devices are of more than one type; or

(v) The requester has not responded to, or has failed to provide a rationale for not responding to, deficiencies identified by FDA in previous submissions for the same device, including those submissions described in § 860.220(a)(3).

(2) If FDA refuses to accept a De Novo request, FDA will notify the requester of the reasons for the refusal. The notice will identify the deficiencies in the De Novo request that prevent accepting and will include the De Novo request reference number.

(3) If FDA refuses to accept a De Novo request, the requester may submit the additional information necessary to comply with the requirements of section 513(f)(2) of the Federal Food, Drug, and Cosmetic Act and this part. The additional information must include the De Novo request reference number of the original submission. If the De Novo request is subsequently accepted, the date of acceptance is the date FDA receives the additional information.

(a) FDA will begin substantive review of a De Novo request after the De Novo request is accepted under § 860.230. Within 120 days after receipt of a De Novo request or receipt of additional information that results in the De Novo request being accepted under § 860.230, FDA will review the De Novo request and send the requester an order granting the De Novo request under § 860.260(a) or an order declining the De Novo request under 860.260(b).

(b) A requester may supplement or amend a pending De Novo request to revise existing information or provide additional information.

(1) FDA may require additional information regarding the device that is necessary for FDA to complete the review of the De Novo request.

(2) Additional information submitted to FDA must include the reference number assigned to the original De Novo request and, if submitted on the requester's own initiative, the reason for submitting the additional information.

(c) Prior to granting or declining a De Novo request, FDA may inspect relevant facilities to help determine:

(1) That clinical or nonclinical data were collected in a manner that ensures that the data accurately represents the benefits and risks of the device; or

(2) That implementation of Quality System Regulation (part 820 of this chapter) requirements, in addition to other general controls and any specified special controls, provide adequate assurance that critical and/or novel manufacturing processes produce devices that meet specifications necessary to ensure reasonable assurance of safety and effectiveness.

(a) FDA considers a De Novo request to have been withdrawn if:

(1) The requester fails to provide a complete response to a request for additional information pursuant to § 860.240(b)(1) within 180 days after the date FDA issues such request;

(2) The requester fails to provide a complete response to the deficiencies identified by FDA pursuant to § 860.230(c)(2) within 180 days of the date notification was issued by FDA;

(3) The requester does not permit an authorized FDA employee an opportunity to inspect the facilities, pursuant to § 860.240(c), at a reasonable time and in a reasonable manner, and to have access to copy and verify all records pertinent to the De Novo request; or

(4) The requester submits a written notice to FDA that the De Novo request has been withdrawn.

(b) If a De Novo request is withdrawn, the Agency will notify the requester. The notice will include the De Novo request reference number and the date FDA considered the De Novo request withdrawn.

(a)(1) FDA will issue to the requester an order granting a De Novo request if none of the reasons in paragraph (c) of this section for declining the De Novo request applies.

(2) If FDA grants a De Novo request, within 30 days after the issuance of an order granting the De Novo request, FDA will publish in the Federal Register a notice of the classification order, including any special controls.

(b) If FDA declines a De Novo request, FDA will issue a written order to the requester.

(c) FDA may decline a De Novo request if the requester fails to follow the requirements of this part or if, upon the basis of the information submitted in the De Novo request or any other information before FDA, FDA determines:

(1) The device does not meet the criteria under section 513(a)(1) of the Federal Food, Drug, and Cosmetic Act and § 860.3 for classification into class I or II;

(2) The De Novo request contains a false statement of material fact or there is a material omission;

(3) The device's labeling does not comply with the requirements in parts 801 and 809 of this chapter, as applicable;

(4) The product described in the De Novo request does not meet the definition of a device under section 201(h) of the Federal Food, Drug, and Cosmetic Act and is not a combination product as defined at § 3.2(e) of this chapter;

(5) The device is of a type which has already been approved in existing applications for premarket approval (PMAs) submitted under part 814 of this chapter;

(6) The device is of a type that has already been classified into class I, class II, or class III;

(7) An inspection of a relevant facility under § 860.240(c) results in a determination that general or general and special controls would not provide reasonable assurance of safety and effectiveness;

(8) A nonclinical study subject to part 58 of this chapter that is described in the De Novo request, and that is essential to show there is reasonable assurance of safety, was not conducted in compliance with part 58 of this chapter and no reason for the noncompliance is provided or, if a reason is provided, the practices used in conducting the study do not support the validity of the study;

(9) A clinical investigation described in the De Novo request involving human subjects that is subject to the institutional review board regulations in part 56 of this chapter, informed consent regulations in part 50 of this chapter, or GCP described in § 812.28(a) of this chapter, was not conducted in compliance with those regulations such that the rights or safety of human subjects were not adequately protected or the supporting data were determined to be otherwise unreliable;

(10) A clinical or nonclinical study necessary to demonstrate that general controls or general and special controls provide reasonable assurance of safety and effectiveness:

(i) Has not been completed per the study protocol, or

(ii) Deficiencies related to the investigation and identified in any request for additional information under § 860.240(b)(1) have not been adequately addressed; or

(11) After a De Novo request is accepted for review under § 860.230(b), the requester makes significant unsolicited changes to the device's:

(i) Indications for use; or

(ii) Technological characteristics.

(d) An order declining a De Novo request will inform the requester of the deficiencies in the De Novo request, including each applicable ground for declining the De Novo request.

(e) FDA will use the criteria specified in § 860.7 to determine the safety and effectiveness of a device in deciding whether to grant or decline a De Novo request. FDA may use information other than that submitted by the requester in making such determination.