FDA Issues Draft Guidance, “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device”July 26, 2011
On July 27, 2011, the Center for Devices and Radiological Health ("CDRH") announced the issuance of a Draft Guidance titled “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device.” When finalized, this guidance document will replace that of the same name issued in January 1997.
At first glance, the 2011 Draft Guidance does not appear to be too different from its 1997 predecessor. For instance, both claim to focus on the meaning of whether a modification may “significantly affect” the safety or effectiveness of the device; both pose questions, categorized by modification category, that are to be analyzed for each change individually as well as collectively since the last 510(k) clearance; and both emphasize that, when determining whether the modifications may significantly affect safety or effectiveness, the modified device may only be compared to the most recently cleared device, not to another device made by the manufacturer or another manufacturer.
But don’t get too comfortable too soon. While much of the Draft Guidance is not too drastically different from the 1997 version, some of the changes that the Draft Guidance does include make fairly substantive changes to existing policy and practice. Most importantly, these changes all flow in one direction: more 510(k)s. Changes that, in the past, may have been addressed via a letter to file may now require a new 510(k). There do not appear to be any situations in which a change that previously required a 510(k) may now be addressed via a letter to file.
Labeling Changes. Let’s start with labeling. In the 1997 guidance, the labeling section notes that the threshold for whether a new 510(k) will be required is whether the modification affects the indications for use. The 2011 Draft Guidance, however, does not appear to be so limiting. Of particular interest is that the Draft Guidance notes that “it is important to keep in mind that the term ‘labeling’ includes more than just the instructions for use,” and may include things such as promotional materials. Presumably, this means that when a manufacturer changes its promotional materials, it will need to go through the labeling analysis in the Draft Guidance and determine whether that change necessitates a new 510(k). If a manufacturer determines no new 510(k) is needed, it will need to document that decision.
In addition to including promotional materials in the types of labeling covered by the Draft Guidance, the labeling section states that CDRH will now require a new 510(k) for changes that were specifically called out as not requiring a new submission in 1997. For instance, the 1997 guidance notes generally that if a device is cleared for three indications and the manufacturer decides to market the device only for two of those indications, no new 510(k) is needed. The Draft Guidance, however, modifies this condition in a manner sure to create confusion, stating that no new 510(k) would be needed in that situation only if the indication was removed “due strictly to marketing reasons” (emphasis in original). In other words, if the market demand changed, resulting in a decision by the manufacturer to pull one of the indications, no new 510(k) would be needed. However, “if a firm decides to market the devices for only two of those [three] indications due to other reasons, for example, changes that have been made to the device that affect the removed indication or because of complaints or corrective actions, FDA would generally consider the removal of the indications for use to be a ‘major change’ that requires a new 510(k).” Yes, you read that right. If the manufacturer makes a modification to a device that affects a use no longer claimed in the labeling, it may still need to submit a 510(k) for that modification unless the deletion was for marketing reasons.
The Draft Guidance also changes CDRH’s position regarding clinical versus home use. CDRH has become increasingly focused on home-use products recently, so this change may not be a complete surprise. Nevertheless, it does revise the 1997 position. In 1997, the guidance stated: “Many prescription devices are used in the home with increasing frequency and the Agency believes that 510(k)s are not necessary to add home-use labeling.” This belief is no more. The 2011 Draft Guidance states: “[C]hanges from prescription use in a clinical setting to prescription use in a home setting” require a 510(k).
Manufacturing Process Changes. One other area of particular import is that the Draft Guidance discusses manufacturing changes, a section not contained in the 1997 guidance. Some of the questions asked in the manufacturing section (related to packing or expiration dating and changes to sterilization) were present in the 1997 guidance in a different section. The primary difference is that the Draft Guidance now asks the manufacturer to consider whether manufacturing processes were part of the original 510(k). If not, you’re in luck—the Draft Guidance says if manufacturing process changes were not part of the original 510(k), chances are any changes to the manufacturing process won’t necessitate a 510(k). But if they were part of the original 510(k), “changes to manufacturing processes that could affect device specifications will likely require submission of a new 510(k).”
Technology, Engineering, and Performance Changes. As expected (or, perhaps, hoped), the Draft Guidance also addresses more types of technology used by medical devices than does the 1997 version. With regard to nanotechnology, the Draft Guidance notes that FDA has not adopted nanotechnology-specific criteria to assist manufacturers in determining when changes require a new 510(k), so instead CDRH asks manufacturers to consult it regarding any nanotechnology-related changes.
Many of the technology-related updates in the Draft Guidance conclude that a new 510(k) would be required for most technology-related changes. For instance, the Draft Guidance concludes that “all changes in fundamental scientific technology could significantly affect safety or effectiveness,” and therefore all such changes require the submission of a new 510(k). The Draft Guidance also more specifically addresses whether the change has the potential to alter performance characteristics or specifications, and concludes that such changes directly impact the performance, and potentially the safety and effectiveness, of the device, “and a new 510(k) with comparative testing should be provided for such modifications, whether the performance characteristics are improved or worsened.” Another area with a sweeping requirement for a new 510(k) is changes that affect how the device receives, transmits, or displays electrical signals or data. The Draft Guidance does not contain much discussion of this topic, but nevertheless concludes that most changes of this nature have the potential to significantly impact safety or effectiveness by altering data communication quality, and therefore require a new 510(k). An example provided includes a case of diagnostic software that typically displays images on a monitor in a clinical setting that is being modified to output the image to a portable hand-held device that can be used to view the images from any location. The Draft Guidance states that this change “could result in new risks, such as the inability to discern certain data due to a smaller hand-held screen, lower picture resolution, or loss of data during transmission, that could significantly affect the safety and effectiveness of the software.”
Finally, the Draft Guidance includes an area into which FDA generally at least attempts to tread lightly: the practice of medicine. One of the questions posed in the Draft Guidance is whether the change will affect how the device is likely to be used in practice. What is particularly interesting about this question is that it cites a little-used statutory provision related to FDA’s ability to consider potential off-label uses of products under review. According to this provision, if FDA concludes there is a “reasonable likelihood that the device will be used for an intended use not identified in the proposed labeling” and that “such use could cause harm,” FDA may require the submitter to include a statement in the labeling providing “appropriate information regarding” the off-label use of the product. According to the Draft Guidance, if a manufacturer makes a change to the product that may result in off-label use that could cause harm, even if the manufacturer does not intend to change the labeling, a 510(k) may be needed “to enable FDA to evaluate whether ‘appropriate information’ in the labeling about a use not currently identified in the labeling is necessary.”
It’s hard to say whether industry will find the Draft Guidance provides the clarity missing from the 1997 guidance, or whether the proposal only increases the areas of ambiguity. The only thing that appears certain is that CDRH believes many more modifications necessitate a new 510(k) than had been the case. There are no changes where 510(k)s that were needed are no longer required, but there are many changes for which companies would have used a letter to file that would now need a 510(k).