Auld Acquaintance; 2017 Guidances and 2018 Enforcement

2017 is now a part of the past, and everyone has their own idea as to which were the most crucial developments of the year. Following is a nomination for two FDA guidances that are at least strong candidates for the title of the most important guidances of 2017, along with developments in two ongoing dramas that could prove pivotal in this new year.

What’s Old is New (yet) Again

The FDA’s Center for Devices and Radiological Health had little to offer in the way of guidances in the first half of 2017, but the center made up for that in a big way in the latter part of the year. CDRH issued 19 draft and final guidances in the last three months of the year, but the month of September was a busy one, too.

Still, the most important guidances might not have been the most widely discussed. The October final guidance for 510(k) changes and the companion software 510(k) changes final guidance might not have the splash value of the agency’s moves in the digital health realm, but it’s easy to forget how long the 510(k) changes controversy has strained relations between the FDA and industry.

Thinking back to the legacy K97 guidance of 1997, this discussion has been the subject of formal regulatory interest for only 20 years despite that the Medical Device Amendments were added to the statute more than 40 years ago. The agency took a stab at rewriting K97 in 2011, but that attempt proved futile thanks to the opposition it triggered.

Traditionally, the estimates of the number of 510(k) clearances each year is somewhere between 3,500 and 4,000, a much greater number than the volume of original PMAs, which hasn’t hit 100 in recent memory, if ever. Are digital health guidances “hotter” in terms of novelty and hence media coverage?

Apparently, but make no mistake: The 510(k) program and the agency’s overarching administration thereof is easily the most important regulatory development in calendar year 2017, particularly given that the new med tech regulations in Europe could drive a lot of traffic back to American shores.

2018: Commercial Speech Comes of Age?

2017 was a regulatory banner year for med tech, thanks to the 21st Century Cures Act and the provisions of the fourth device user fee agreement, so it’s difficult to see how 2018 can measure up. Still, this new year has at least one blockbuster story in store if recent remarks by FDA commissioner Scott Gottlieb are any indication.

Gottlieb said the agency needs “a legally enforceable set of rules” where commercial speech is concerned, a nod to recent court losses, such as Caronia. Hence, Gottlieb’s said the FDA “can’t be operating from a platform where our regulations might be perpetually in conflict with the courts.”

The agency’s January 2017 draft guidance for payer communications is still in draft form, but that’s to be expected with the change in the commissioner’s office, particularly a commissioner with Gottlieb’s views on the commercial speech question. Another consideration is that a payer communication framework might be the lowest hanging of the several commercial speech questions, and there was little indication at the time that the FDA had adopted a less restrictive approach to off-label communications to physicians.

Gottlieb’s comments from September 2017 suggest he wants the agency to provide industry with some rules of the road for the entirety of the commercial speech problem, but the agency’s chief counsel, Rebecca Wood, avoided the subject in her prepared remarks to a gathering of the Food and Drug Law Institute in early December 2017. The net effect is something of a black box inside which the regulatory version of Schrödinger’s cat awaits our collective scrutiny, but Gottlieb seems determined to settle this matter by one means or another, even if there is some understandable skepticism as to the durability of any resolution. This is a matter worth watching as we move into 2018.

Yates Memo; Up for Grabs?

On the other hand, those who are concerned about a hangover from the Yates memo might be encouraged by the fact that FDA’s Woods conceded that it is time for the FDA to revisit the question of vicarious criminal liability in Park doctrine cases. The question here is whether the agency and the Department of Justice are on the same page, given that these two parties have not necessarily agreed on these issues in the past.

The corporate liability question seems ripe for review if only because Sally Quillian Yates is no longer at the Department of Justice, but deputy attorney general Rod Rosenstein acknowledged that the Yates memo is under review in a speech to the Heritage Foundation in September 2017. Although he offered no details other than to affirm that prosecution of individuals is still seen as important as a deterrent, he stated, “I do anticipate that we may in the near future make an announcement about what changes we are going to make to corporate fraud principles.”

Rosenstein confirmed in an October 2017 speech to New York University that the memo is still in play, explaining that any changes “will reflect our resolve to hold individuals accountable for corporate wrongdoing.” However, Rosenstein also said federal attorneys will not be permitted to “use criminal authority unfairly to extract civil payments.”

While there are few tea leaves to work with, the statement about the use of criminal authority to extract civil payments is at the very least some indicator as to where DoJ may be headed. On the other hand, there are those who worry that the prison sentences handed down in the case of Jack De Coster and Peter De Coster could be part of an emerging pattern despite that the De Costers’ egg businesses routinely and egregiously ran afoul of the law over a period of decades. The corporate prosecution story is clearly another story worth tracking as we work through this new year.

Digital Desires; the FDA’s December Guidance Trove

The end of the year is a time for reflection and maybe even gratitude, but as we can all testify, holiday shopping can be an irritating experience. The FDA got an early start on its holiday shopping list in the first week of December with the publication of several guidances as part of the overhaul of its approach to digital health. As might be expected, though, the experience is a decidedly mixed bag of items, one of which seems likely to be returned for exchange.

SaMD Final: A Leaner, Nicer Approach

On the positive side, the final guidance for software as a medical device (SaMD), the draft of which was written by the International Medical Device Regulators Forum, eliminates some of the seemingly compulsory tone of the draft. Nonetheless, the FDA went to some lengths to emphasize in the final that industry should not read too much into the use of words such as “requirements,” explaining that related provisions fall into the category of recommendations. Given the recent congressional emphasis on the least burdensome standard, the agency perhaps had little choice but to make such a conciliatory gesture.

The final SaMD guidance is 15 pages leaner than the draft (30 pages rather than 45), and large portions of the draft have either slimmed down or disappeared entirely. Definitions have become less descriptive, thus lending an unmistakable air of flexibility to the document. Whereas the draft commits page after page to discussions of generating evidence for scientific and analytical validity, the final guidance offers mere paragraphs for considerations such as analytical and technical validation.

The net effect is that of a high-level document that avoids the quagmire associated with the fine details of product development and testing. Whether this is the last word for some time on SaMD is difficult to forecast, but the reader will note that the agency took the unusual step of announcing the final guidance in the Federal Register, complete with the associated docket number.

The Risk of Saying Nothing About Risk

Conversely, the draft guidance for clinical decision support (CDS) systems presents the reader with a decidedly different dilemma, although it offers some useful content. The draft includes a section spelling out instances in which a CDS would not fall under FDA regulations, such as software that provides recommendations as to the use of a drug within the labeled indication. This document also provides a number of examples of uses of a CDS that would qualify the item as a device, but Bradley Merrill Thompson of Epstein Becker Green had a few choice words regarding the draft.

Thompson, who serves as the general counsel for the CDS Coalition, said the CDS draft lacks clarity on the point of how a vendor might determine how the risks associated with that product’s use might push the CDS into the agency’s regulatory territory. Thompson said this is particularly problematic given the recent and coming advances in artificial intelligence, although others indicated some relief that patient use of CDS was written into the document.

One way of looking at the risk question in this guidance – or more properly, the failure of the draft to directly address the risk question – is that the agency believes it might be a more economical use of its time to draw feedback from stakeholders before committing anything to ink. The docket is open for only sixty days, however, and it seems fairly plausible that the Feb. 6, 2018 deadline for comment will be extended if indeed the FDA intends to provide at least some discussion of risk. After all, the agency’s device center has expended a considerable amount of effort to talk about benefits and risks, including the final guidance on how the FDA will handle the hazards of dealing with problematic devices that may or may not warrant withdrawal.

The last of the three guidances released by the FDA on Dec. 7 was the draft guidance dealing with policy changes to four existing guidances, including the guidance for medical device data systems (MDDS). The agency’s proposal to regulate such software in 2011 sparked a lot of pushback from stakeholders with a lot of bandwidth on Capitol Hill, and the agency walked back from several major features of its early proposals several years ago. This guidance will be substantially revamped, although in its current form it is apparently not operational, as the saying goes.

The general wellness app guidance is also scheduled for a thorough rewrite, as are the guidances for mobile medical applications and off-the-shelf software used in medical devices. Device makers have the 21st Century Cures Act to thank for much of this, but the agency’s latest commissioner, Scott Gottlieb, might have pushed for many of these changes even without the help of the Cures Act. All in all, Dec. 7 was not a bad start to the holiday season, even if one or two items will eventually be re-gifted to the giver.

FDA Issues New Guidance on 3D Printing of Medical Devices

Jordan Lipp, Esq. | Partner, Davis Graham & Stubbs

Today, the FDA issued new guidance for the industry on 3D printing of medical devices, entitled “Technical Considerations for Additive Manufactured Medical Devices.”  Considering the recent advances in 3D printing technology, especially with anatomically-matched devices that are built for individual patients, FDA guidance on this issue is welcome.  The guidance provides the FDA’s current thinking on the myriad of issues from material controls, process validation, and device testing, to cybersecurity.

This guidance also provides information on labeling considerations involving 3D printed medical devices.  With regards to patient-matched device, the FDA recommends that additional labeling be provided with:

  • patient identifier,
  • use (e.g., left distal femoral surgical guide), and
  • final design iteration or version used to produce the device.

Also, with regards to labeling, the FDA recommends both reviewing whether the expiration date is the same as the typical shelf life for a non-patient-matched device and including a precaution that the patient should be surveyed for potential anatomical changes prior to the procedure.

The newly issued guidance is just a stepping stone.  As the FDA noted in its press release, “our recommendations are likely to evolve as the technology develops in unexpected ways.”  And, of course, as this is a guidance document, so it is nonbinding.

New Guidance from FDA: When to Submit a 510(k) for a Change to a Cleared Medical Device

Courtney A. Stevens, Esq. |Senior Attorney, Medmarc Loss Control

FDA’s newest guidance for medical device manufacturers, Deciding When to Submit a 510(k) for a Change to an Existing Device, issued August 8, addresses a question manufacturers commonly face,—when a 510(k) is necessary for a change to an already cleared device. Manufacturers’ failures to submit 510(k)s are frequently cited in warning letters as rendering a device adulterated. As such, it’s an issue medical device companies can’t be too careful in scrutinizing. Thankfully, this guidance does provide such much-needed clarity on exactly when a 510(k) is necessary, and when processing the change in accordance with Quality System (QS) requirements (e.g., documentation of changes and approvals in the master record, verification and revalidation, etc.) is sufficient.

The confusion over whether a 510(k) is necessary is largely due to the subjective, relative language in the regulations, requiring device-makers to submit a 510(k) when a change “could significantly affect the safety or effectiveness of the device.” (21 CFR 807.81 (a)(3)). The Agency tried to clarify its interpretation of that language in its first guidance document on this issue, published in 1997, but clearly, as evidenced by the frequency with which the manufacturers’ determination of “significant” changes differed from the Agency’s, greater clarity was needed still. (Once finalized, this draft guidance will supersede the 1997 Guidance on the subject.)

This guidance document improves upon its predecessor by providing a number of exacting flow chart-decision trees to guide manufacturers through the determination of a 510(k)s’ necessity with regard to different types of changes.

It begins by setting out the guidance principles to be first considered in determining the propriety of a 510(k), which I briefly summarize here:

  • Modifications made with intent to significantly affect safety or effectiveness of a device. This is the same language as is found in the regulations, and its meaning is fleshed out in the remainder of the document.
  • Could “significantly affect” evaluation and the role of testing. In order to determine significance of the effect, manufacturers must conduct risk-based assessments.
  • Unintended consequences of changes. One component deemed to make up a “significant effect” is if the change would result in unintended consequences or effects. The draft guidance provides sterilization as an example which may affect device materials, thereby affecting performance of the device.
  • Use of risk management. Here, the draft refers to ISO 147981: Medical devices – Application of risk management to medical devices, and instructs manufacturers to utilize an assessment combining the probability of occurrence of harm and the severity of that harm in determining “significant effect.”
  • Evaluating simultaneous changes. Even though changes may occur simultaneously, each change should be assessed individually and in combination.
  • Appropriate comparative device and cumulative effect of changes. In making the determination of a 510(k)’s propriety, manufacturers need to consider (1) how different a change makes the device from its initial or most recent iteration as described in their most recently cleared 510(k); and (2) the cumulative effect of all changes since the last 510(k) cleared for this device. That is, though previous changes did not require a 510(k) when made in isolation, does the cumulative effect of this change with those previously made nor warrant a 510(k), even if it, by itself, would not?
  • Documentation required. Even if a manufacturer determines a 510(k) is appropriate for a particular change, this does not alleviate them from compliance with all existing QS requirements, including all documentation, verification, and validation duties.
  • 510(k) submission for modified devices. When a 510(k) is submitted for a device with multiple modifications since its last cleared 510(k), the 510(k) should describe not only the most recent change that warranted the 510(k), but also all previous modifications even though they did not merit the submission of 510(k)s in and of themselves.
  • Substantial equivalence determination. Manufacturers need understand that submission of a 510(k) for a change pursuant to everything outlined in the regulation and this guidance document does not assure that a substantial equivalence determination will be provided.

 

With these considerations in mind, manufacturers may proceed to the different parts of the guidance instructing them on decision-making for different kinds of changes—labeling, control mechanisms, operating principles, etc. In each of these, manufactures will find the aforementioned decision trees to guide them through submission criteria.

An example of the flow charts included in this draft guidance:

8.16 - guidance flowchart

In addition to charts guiding decision making, the guidance also provides examples of documenting changes and written regulatory change assessments.

This should go a long way in facilitating manufacturers’ understanding of when 510(k)s for changes are necessary, and reduce the number of warning letters for companies’ failure to submit them, accordingly.