Seven Mistakes that can Delay Your FDA 510(k) Clearance
Based on data provided by the US Food and Drug Administration as well as Emergo consultants’ experience with medical device manufacturing clients seeking US marketing approval, seven major issues have been identified as the most common perennial causes for delayed premarket notification applications.
Manufacturers whose 510(k) applications contain any one of the following deficiencies will likely face delayed clearance for their devices by the FDA.
- Inadequate device description: Every 510(k) submission must include a description of what the device is intended to do. Without an adequate device description, FDA reviewers cannot determine whether the device has been evaluated properly by the applicant or sponsor. In other words, if a reviewer cannot tell from the submission what the device does, that reviewer cannot determine if the documentation included in the 510(k) submission supports the device’s intended use. It is therefore crucial that applicants provide thorough and clear descriptions of their devices. Without an adequate device description, a substantive review of a 510(k) submission cannot be performed.
- Discrepancies throughout submission: Discrepancies in device descriptions or indications for use can have a substantial impact on device reviews because under the 510(k) pathway, intended use and technological characteristics of a new device are compared to those of a predicate device. When an indications for use statement is inconsistent in different parts of a 510(k) submission—cover letter, indications for use form, 510(k) summary, labeling—FDA reviewers cannot determine if a device has the same indications for use as its predicate, or if any differences change the intended therapeutic or diagnostic effect of the new device when compared to the predicate. Discrepancies preclude substantive review of a submission and require clarification.
- Problems with indications for use: Substantial equivalence requires an applicant’s device to either have the same intended use as a predicate device, and preferably the same or very similar Indications for Use as the predicate. If any differences between the indications for use of the applicant’s device and that of its predicate do exist, those differences must not alter the intended use—that is, the device’s intended therapeutic or diagnostic effect. Furthermore, the type of performance data needed to assess substantial equivalence depends upon the indications sought. A clear indications for use statement is therefore necessary to determine whether methods used to accurately evaluate the device reflect its intended use. Common examples of this problem include lack of identification of a predicate device for the applicant’s device indications; indications that actually require Premarket Approval (PMA); and, in cases of combination device-drug products, inconsistencies between indications for use statements of device and drug components.
- Failure to follow or address current guidance or recognized standards: The FDA frequently issues guidance documents and maintains a list of officially recognized national and international standards in order to help manufacturers determine what information to include in their 510(k) applications. If a manufacturer fails to follow up-to-date guidance for a specific device type or recognized standard without any explanation for doing so, FDA reviewers would issue that manufacturer an Additional Information (AI) letter quoting current guidance in order to obtain that missing information.
- Inadequate or missing performance or clinical data: Performance testing data is required for all traditional 510(k) submissions. In addition, for some device types the FDA requires clinical performance data to demonstrate substantial equivalence. Without adequate performance testing information, FDA reviewers cannot evaluate whether a device’s performance is substantially equivalent to that of its predicate device.
- Comparison to predicate is missing or inadequate: A successful 510(k) submission requires applicants to clearly demonstrate substantial equivalence of their devices to predicate devices already marketed in the US. The FDA expects not only a comparison of similarities, but also a discussion of why differences don't raise new questions of safety and effectiveness. Failure to provide thorough information supporting a selected predicate device—or not providing it at all—will clearly stall an applicant’s 510(k) submission until such information is included.
- Other testing data is missing or inadequate: Testing data unrelated to clinical or performance testing, such as sterilization, software validation and biocompatibility, may also be required in 510(k) submissions for some device types. Premarket notification submissions with incomplete or missing required testing data can thus delay FDA review until applicants provide adequate information.
In-depth Emergo analysis of FDA data on 510(k) review timeframes and related issues can be found here.