On September 9, 2019, the Food and Drug Administration released a final guidance document, Acceptance Review for De Novo Classification Requests, to clarify the content that companies need to include in de novo requests to meet a minimum threshold of acceptability for substantive review. The guidance is meant to create a more efficient product review process by encouraging better submissions. The guidance also provides FDA staff with a consistent approach for making an “Accept” or “Refuse to Accept” determination on a de novo request. The guidance includes both an Acceptance Checklist and a Recommended Content Checklist, both of which will be explained in further detail below.
This Bulletin will provide a high-level overview of the checklists and FDA’s guidance document. It is not an exhaustive overview of the acceptance review process. For background purposes, the de novo process is a regulatory pathway meant to classify new medical devices for which there is no legally marketed predicate device. Devices for which there are no existing predicate devices are presumptively Class III medical devices required to obtain premarket approval. A manufacturer, however, may submit a de novo classification request to have the devices classified into either Class I or Class II based on a risk-based assessment. If the medical device is classified into Class I or Class II, the device may be marketed and used as a predicate device for future premarket notification submissions.
Acceptance Checklist – Preliminary Questions
FDA staff will use the Acceptance Checklist contained in the Appendix to the guidance document to ensure that the de novo request is administratively complete. For a request to be accepted, all administrative elements that are considered acceptance items are required to be included (or the reasoning offered for why the acceptance items cannot be provided). The agency recommends that requestors complete and submit the checklist with the de novo requests and identify the location of supporting information for each acceptance element. Requestors must also include the required user fee and include a validated eCopy for a request to be considered complete.
The following questions are included on the first page of the Acceptance Checklist and should be answered by the lead FDA reviewer as an initial screening of the de novo request:
- Is the product a “device” (as defined in the Federal Food, Drug, and Cosmetic Act) or a combination product (as defined in 21 C.F.R. § 3.2(e)) with a device constituent part subject to review in a de novo request?
- Is the de novo request with the appropriate FDA Center?
- If a Request for Designation (RFD) was submitted for the device or combination product with a device constituent part and assigned to the appropriate Center, identify the RFD number and confirm the following:
- Is the device or combination product the same (e.g., design, formulation) as that presented in the RFD submission?
- Are the indications for use for the device or combination product identified in the de novo request the same as those identified in the RFD submission?
- Is the de novo request for a combination product that contains as a constituent part a drug that has the same active moiety as an approved drug with exclusivity as described in the FD&C Act?
- Is this device type eligible for de novo classification?
- Is there a pending premarket notification (510(k)) or premarket approval (PMA) application for the same device with the same indications for use?
- Is the requester subject to the Application Integrity Policy?
Acceptance Checklist – Organizational Elements
The Acceptance Checklist also contains a number of organizational elements, but notes that failure to include the organizational element items should not result in a “Refuse to Accept” designation. The organizational elements include: (1) the table of contents; (2) specified labeled sections; and (3) numbered pages of the de novo request so that information can be referenced by page number.
Acceptance Checklist – Elements of a Complete De Novo Request
For the following items, FDA has discretion to make a “Refuse to Accept” determination if the item is not included in the de novo Request:
- Administrative Information
- The request must contain a description of the device’s intended use, with prescription or over-the-counter use designated
- Combination Product Provisions, if applicable
- Device Description
- A description of the technology (features, materials, and principles of operation) for achieving the intended effect
- A description of proposed conditions of use; surgical technique for implants; anatomical location of use; user interface; how the device interacts with other devices; and how the device interacts with the patient
- A list and description of the components, parts, and accessories to be marketed with the device
- If the device is an In Vitro Diagnostic, the de novo request should provide the following descriptions as appropriate:
- Sensitivity (detection limits, Limit of Blank), Limit of Detection, Limit of Quantitation where relevant for the device type)
- Analytical specificity
- Classification Information and Supporting Data, including information on the following topics:
- Description of why general controls or general and special controls provide reasonable assurance of safety and effectiveness
- If Class II is recommended, identify proposed special controls and how they provide a reasonable assurance of safety and effectiveness
- Reprocessing and Sterilization information
- Shelf life data or support
- Biocompatibility information
- Software, including level of concern and rationale for the software level of concern
- Information on electrical safety and electromagnetic compatibility
- For animal studies, a statement that the study complies with the Good Laboratory Practice for Nonclinical Laboratory Studies regulation, or if noncompliance with the GLP regulation, explain why the noncompliance would not impact the validity of the study data
- A statement of Compliance for Clinical Investigations
- Overview of literature relied upon in the de novo request and how the literature is applicable in supporting the request
- Benefit-Risk assessment from use of the device and probable risks from such use
- Financial Disclosure Information
- As required by 21 C.F.R. Part 54, the requester must either provide:
- A signed and dated Certification Form (Form FDA 3454); or
- A signed and dated Disclosure Form (Form FDA 3455).
Recommended Content Checklist
FDA recommends including the Content Checklist with a de novo request. The Content Checklist serves as a tool to ensure that the following items are included in the de novo request:
- Administrative Information
- Device Description
- Alternative Practices and Procedures , i.e., existing alternative practices or procedures used in diagnosing, treating, preventing, curing, or mitigating the disease or condition for which the device is intended or which similarly affect the structure and function of the body
- Classification Summary explaining why the subject device is eligible for de novo classification
- Classification Information and Supporting Data
- Labeling that describes the device, its intended use, and the directions for its use
- Statements, Certifications, and Declarations of Conformity
The agency will complete acceptance review within 15 calendar days of receipt of the request. If FDA does not complete the review within 15 calendar days, it will notify the requester electronically that it has not completed the review.
- The guidance document is intended to provide guidance for the submission of an acceptable de novo request for substantive review. It does not change the process by which devices are classified according to such a request once accepted for substantive review.
- To ensure a timely review process, we recommend using the guidance document and checklists to enhance the quality of the request.
For questions, please contact Alan Minsk.