FDA Releases Final Guidance on Interoperable Devices

Courtney S. Young, Esq. |Senior Attorney, Medmarc Risk Management

Last week, the FDA released its final guidance on “Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices.” The draft of this document was issued on January 26, 2016.

The document begins with FDA’s acknowledgment of the increasing prevalence of interconnected medical devices and a statement that “FDA intends to promote the development and availability of safe and effective interoperable medical devices.” It then defines interoperability in this context as “the ability of two or more products, technologies, or systems to exchange information and to use the information that has been exchanged. It relies on § 201(h) of the FD&C Act for the definition of interoperable medical device.

Regarding potential harms associated with errors in interoperability, the guidance provides the example of “transmission of weight in kilograms [by one device] when the receiving medical device assumes the measurement is in pounds” and states that such an error “could lead to patient harm and even death.”

Design Considerations for Interoperable Devices

The guidance highlights the following considerations as appropriately tailored “to the selected interface technology, and the intended use and use environments for the medical device.” I will provide some of the elements the guidance lists under each consideration.

  1. Purpose of electronic interface
  • Types of devices that it is meant to connect to
  • Need for time synchronization
  • What the user should or should not do with the electronic interface including contraindications, warnings, and precautions on the use of the exchanged information
  • Functional and performance requirements of the device as a result of the exchanged information
  • The transmission of metadata (UDI, software version, configuration, settings).
  1. The anticipated user (and what information each user group needs to know)
  • Users, operators, and clinicians need to know the clinical uses and potential risks relevant to the use environment and the clinical task at hand;
  • Equipment maintenance personnel and hospital clinical engineers need to know what actions to take to verify correct configuration
  • Patients may need specific instruction son how to use their device in a home environment
  1. Risk management considerations
  • Whether implementation and use of the interface degrades the basic safety or risk controls of the device
  • Whether appropriate security features are included in the design
  1. Verification and validation

A manufacturer should:

  • Verify and validate that when data is corrupted is can be detected and appropriately managed;
  • Perform testing to assure that the device continues to operate safely when data is received in a manner outside of the bounds of the parameters specified.
  • Verify only authorized users (individuals, devices, systems) are allowed to exchange information with the interoperable device
  • Assure that reasonably foreseeable interactions do not cause incorrect operation of other networked systems
  1. Labeling considerations
  • The manufacturer should determine the appropriate way to provide the information based upon the anticipated users and the risk analysis.
  1. Use of consensus standards
  • FDA recognizes the benefits of relying on published consensus standards in the design of medical devices, in general, and in the development of interoperable medical devices, in particular.

Recommendations for Contents of Pre-Market Submissions

The last part of the guidance focuses on what manufacturers of interoperable devices should include in their pre-market solutions. The guidance elaborates on each of these elements: device description, risk analysis, verification and validation, and labeling.



Life Sciences News Roundup, 6/22

Courtney S. Young, Esq. | Senior Attorney, Medmarc Risk Management

MedPAC Calls for Action to Reduce Number of PODs 

On June 15, the Medicare Payment Advisory Commission (MedPAC) issued its annual report, which enumerated problems with PODs and outlined actions that could be taken to reduce their prevalence. You can read more here.

FDA Seeks Comment on Two New Drug Promotion Studies

The FDA published two notices in the Federal Register on Monday articulating its plans to undertake new studies on drug promotion: (1) Experimental Study on Risk Information Amount and Location in Direct-to-Consumer Print Ads; and (2) Disclosures of Descriptive Presentations in Professional Oncology Prescription Drug Promotion.


FDA Back in the News Sans Guidances

After a drought in terms of guidances and other regulatory documents, the FDA is back in the news in a big way in the week of May 8, although there are no guidances or other regulatory documents at play. It’s tempting to try to read a lot of things into some of these developments, but other developments seem to hint at a need for more investment for not necessarily more return.

Gottlieb; same old thing or something different?

Former FDAer Scott Gottlieb is the back at the FDA, this time in the commissioner’s chair, thanks to his successful navigation of the Senate minefield. The opposition to Gottlieb included allegations that he will run roughshod over the drug and device review processes, and that he is “a doctor with ties to the drug industry.” Of course, Robert Califf was also a doctor with ties to the drug industry, but try finding a doctor who doesn’t have those ties. FDA advisory committees wrestle madly trying to find such a unicorn so they don’t have to go through the irksome vetting process.

On the other hand, there are those who hail Gottlieb as a breath of fresh air and a much-needed source of level-headedness at the agency. The trade associations issue the usual bland statements such as “we look forward to working with” Gottlieb, but they are not publicly predicting any radical changes at the agency under him, and they shouldn’t.

Anyone who hopes Gottlieb will effect an immediate transformation of the agency’s outlook on product reviews or on commercial speech would do well to remember how much difficulty the agency’s managers have had with the rank-and-file in times gone by. We might recall the letters from device reviewers to the Obama administration and a couple of members of Congress back in 2009, which stirred the political pot quite vigorously. However, the accompanying allegations of regulatory misconduct never quite stuck, and those letters – replete as they were with trade secrets – cost more than one FDA employee their job.

Nonetheless, it took quite some time for the agency to root out those problems, so there are many reasons to be skeptical about an impending change of “culture.” Jeff Shuren, director of the FDA device center, pointed to this cultural difficulty in a recent hearing regarding the user fee agreement, and he should know. He took over the directorship of the Center for Devices and Radiological Health shortly after the FDA renegades started stirring up controversy eight years ago, and despite industry’s misgivings about him in the first couple of years, Shuren was in no mood for the misadventures of these malcontents. Still, it took some time before he was able to give anyone the heave-ho.

User fee bills passed

The Senate HELP Committee put the user fee legislation in a nice, tidy bundle for consideration of the full Senate thanks to a May 11 markup, but there is one provision therein that might have some interesting effects on clinical trials in the years to come.

Sen. Orrin Hatch of Utah proposed an amendment that would require that the FDA mandate that clinical studies both offer greater access to several demographics, including infants and children, while also stipulating that clinical study enrollment more accurately reflect the population that would receive the treatment in question. This amendment, which passed on a voice vote, will also streamline IRB review of individual petitions for access to an investigational product.

It might be argued that there’s a tension of sorts between broader access and ensuring that enrollees reflect real-world usage, but either way you cut it, enrollment in clinical studies seems certain to increase. Needless to say, this could substantially increase the cost of a clinical study, which in the case of some medical devices can easily exceed $50,000 per enrollee.

It’s not clear how this pays off for industry, however, given that the additional enrollment required by the FDA might be of patient subgroups that exhibit a differential response. Supposing this subgroup experiences a lower therapeutic effect than the patient population as a whole, but that the sponsor cannot enroll enough members of this sub-group to allow for a separate analysis?

As for access by individuals, one has to wonder whether IRBs will be swamped with individuals applying to take part in a study for which they might not be a natural fit. Patients aren’t exactly bashful these days, after all, and it does not stretch the imagination to think that IRBs end up with a lot more work to do. Will the additional workload interfere with an IRB’s review of a drug or device study proposal?

Liability in EU Market Promises to Grow

Device makers doing business in the U.S. don’t always care for the current state of tort law, but at least they know what to expect. The legal environment in other markets is undergoing some changes that promise to up the ante where financial liability is concerned.

The European Parliament recently voted on the overhaul of device regulations for the European Union, bringing to a close an effort of several years’ duration. As has been previously described at this blog, the notified bodies have their own recent issues with liability in the EU nations, but one of the less conspicuous features of the new Medical Device Regulations is that device makers will have to ensure they can make compensation to all patients who have been harmed by defective medical devices.

The version of the new regulatory framework adopted by the EP includes a requirement that device makers develop “a robust financial mechanism” that will compensate patients who “receive defective products.” There are several factors that go into the calculation of that “robust” mechanism, including the class of the device and the associated risk, but the legislation also points to the size of the manufacturer as a factor. The legislation further stipulates that device makers put themselves in a position to “rapidly and effectively” compensate patients, even when the company has gone out of business.

It requires no reading of tea leaves to realize this provision was sparked at least in part by the silicone gel breast implant scandal, which gained momentum in 2009 when implant rupture rates began to spike. The manufacturer, Poly Implant Prothèse, went bankrupt the following year. The metal-on-metal hip implant problem might also have figured into this provision.

The summary for this legislation is not specific about the nature of this financial mechanism, so it would appear that liability policies will serve in the stead of cash reserves. Whether a manufacturer opts to self-insure or cover this requirement by other means, one thing companies cannot do is leave themselves open to a raft of lawsuits without some sort of plan in place to deal with any claims.

Company beats shareholder suit despite CIA

Minnesota-based Cardiovascular Systems, Inc., persuaded a federal judge to toss out a class-action shareholder lawsuit based on alleged illegal sales tactics, but the suit may be refiled. District Court judge Donovan Frank dismissed the suit (Shoemaker v. Cardiovascular Systems) due to the absence of information specific enough to support the allegations, but Frank left the door open to a reopening of the suit. Cardiovascular had already settled a qui tam lawsuit with the federal government in the amount of $8 million, but the company is also working under a five-year corporate integrity agreement with the Office of Inspector General at the Department of Health and Human Services, which went into effect in June 2016.

PTO to revisit controversial AIA program

Holders of patents who have grown fatigued with the inter partes review process at the U.S. Patent and Trademark Office may be relieved to know the PTO is undertaking a retrospective review of this and other procedures handled by the agency’s Patent Trial and Appeals Board (PTAB). The inter partes review, one of several functions added to the PTO’s to-do list via the America Invents Act (AIA) of 2012, has been widely blasted as doing little to slow down the stream of cases landing at the Court of Appeals for the Federal Circuit, but also for allowing parties with no direct interest in a patent to damage or destroy the patent.

Hedge fund billionaire Kyle Bass has not been uniformly successful with the inter partes process, losing a challenge to the patent for Shire’s Lialda (mesalimine) late in 2016, but Bass has managed to invalidate a number of important patents via the process. PTO director Michelle Lee has instructed PTO staffers to review issues such as multiple petitions, motions to amend, and claims construction. The PTO announcement did not identify a date by which the review would be complete, however.

FDA’s Interesting Off-Label Memo


The FDA recently posted a memorandum spelling out the agency’s views regarding off-label promotions, a document chock full of interesting observations. This discussion is now taking place in a somewhat different political backdrop, however, particularly in light of the dismissal of a high-ranking and well-known member of the Department of Justice. The picture in aggregate is highly fluid – which may or may not portend change – but which nonetheless is almost certainly unsettling to those at the FDA who prefer the status quo where off-label promotion is concerned.

When a solution is not a solution

The January 2017 FDA off-label memo offers the expected rationale for the agency’s current views on commercial speech, including that the requirement to conduct studies of a drug or device for a specific indication does a lot to provide assurance that the therapeutic in question will do more good than harm.

The memo takes a turn for the peculiar, however, when the FDA takes credit for things such as patent protection, which most would say redounds to the credit of the statute and the Patent and Trademark Office. Subsequently, the memo offers alternatives to the current state of affairs, such as a ban on off-label use of drugs and devices, and the application of a higher level of taxation on off-label use.

The problem with these and a couple of others of the FDA’s alternative commercial speech universes is that they are entirely outside the agency’s jurisdiction. For instance, it is quite well known that off-label use is within a physician’s discretion, and doctors are not regulated by the FDA. Not yet, anyway. As for tax policy, there’s no need to explain why this is outside the agency’s statutory authority.

There are several items of interest where context is concerned, not the least of which is that Robert Califf has resigned from the FDA commissioner’s chair, leaving the Trump administration with a very interesting job to fill. A number of names have been floated for that opening, including that of Scott Gottlieb, whose curriculum vitae includes a stint as one of the FDA’s deputy commissioners. Gottlieb has voiced reservations about the agency’s standards regarding off-label speech, but other candidates of record, including venture capitalist Balaji Srinivasan, are unknowns where the off-label discussion is concerned.

All in all, attorneys at the FDA have to assume the commercial speech question is likely to weigh against the agency in the months and years ahead, even if nothing in the way of legislation surfaces.

More than one new face at DoJ

One interesting bit of context here is the dismissal of Sally Quillian Yates, she of the famed Yates memo, which some believe comes up only a little short of the extortive tenor of the Thompson memo. President Trump gave Yates the axe for announcing that DoJ would not mount a legal defense of the administration’s executive order on immigration from six nations said to harbor terrorists. Whatever one believes about that executive order – and it should be noted that recent developments do not necessarily portend a revisitation of the memo that bears Yates’ name – her dismissal sends an unmistakable signal that employees of the federal government can press their luck only so far.

Clearly it’s too early to anticipate what will become of the off-label discussion, but this issue has occupied a tremendous amount of time and effort at the FDA, and these developments can’t help but embolden adversaries of the agency’s current stance on the commercial speech/First Amendment question. Change may or may not be in the offing, but it needn’t start with the executive branch of the federal government. It may come in the courts, and whomever the Trump administration appoints to the job of solicitor general may have some very interesting things to say, indeed, if the matter ever reaches the Supreme Court.

Compliance Benefit-Risk Final Retains ‘Industry-Wide’ Language

The FDA managed to wrap up the guidance for benefit-risk determinations for compliance action in six months, a much shorter turn-around than seen in a number of recent medical device guidances. The agency unveiled the final version just in time for the holiday season, but device makers should be aware that this guidance states that one company’s problem can quickly become a problem for other device makers.

Alignment with ISO 14971 spotty

The agency stated in the June 2016 draft that the intent was to “provide clarity” for the agency and device makers on the factors to be considered regarding compliance and enforcement activities for devices that seem to be emitting problematic safety signals in the postmarket realm. Among the factors taken into consideration is the prospect that a withdrawal would create a shortage of essential medical devices, and the FDA indicated from the outset that both short- and long-term considerations must be taken into account when examining whether the benefit-risk profile of a device seems to suggest a need for compliance and/or enforcement activity.

The final guidance did nothing to align more tightly with ISO 14971 than the draft, a consideration cited by several trade associations as a significant problem with the draft. In both versions of the guidance, the FDA acknowledged the roles of both ISO 14971 and 21 CFR Part 820 in terms of total life cycle management, but the final guidance has little more to say about this other than to concede that alignment of the Quality Systems Regulations with the ISO standard is limited.

Device makers had argued through their trade associations that the failure to provide more specific information on this score makes it difficult at best to anticipate how compliance with the ISO standard would satisfy the agency when using 14971 in determining how to address a problematic or potentially problematic device, all to no apparent avail.

Why your problem becomes my problem

Perhaps of greater interest to device makers, however, was the section appearing in both versions stating that any hazards associated with a specific device could be extrapolated to other devices made by that manufacturer, and to any similar devices made by other manufacturers. The FDA did not specifically state that any compliance and enforcement activities mandated by the agency would necessarily extend to similar devices made by other companies, but those in the life science industries are all too aware that bad news announced by a federal agency can quickly become a contagion in the court of public opinion. In some circumstances, the FDA may feel pressured to act on an individual company’s offerings even in the absence of a clear safety signal specific to that company’s device.

It might be pertinent to point out that members of the Senate and the House of Representatives occasionally dive into the med tech regulation pool, such as when Sen. Patty Murray (D-Washington) introduced the Preventing Superbugs and Protecting Patients Act of 2016 despite that the agency had mandated postmarket surveillance studies of duodenoscopes in late 2015. The savvy device manufacturer might consider the possibility that the FDA would prefer to undertake more vigorous – and potentially more sweeping – enforcement action rather than deal with further congressional meddling when adverse events reports begin to spike for a competitor’s offerings.

Legal Standing Aside, FDA Inks Emerging Signals Final Guidance

The FDA needed a year to move a draft guidance for emerging medical device safety signals to final form, assuring industry along the way that such disclosures would be handled deftly. At least one trade association raised the question of whether the agency enjoys the statutory authority to issue such advisories in the first place, but as a physician might say, the best medicine for this kind of issue is still prevention.

Statutory authority question gains no traction

The Center for Devices and Radiological Health published the draft “emerging signals” guidance in December 2015 with the acknowledgement that such advisories could lead to a problematic degree of under-utilization. The agency’s argument was that the benefits of such a disclosure would outweigh the risks, perhaps a nod to the benefit-risk draft guidance for regulatory action, which the agency may believe is a necessary companion piece to the emerging signals guidance.

One of the device associations that commented to the docket for the draft guidance argued that the Medical Device amendments do not authorize the disclosure of potential device safety information in the same manner as is found in the provisions governing drug regulation. Another device association asserted that any such announcements by the FDA would be arbitrary and capricious – which by precedent would seem to invite a lawsuit – or at the very least that such a move on the FDA’s part is more appropriately handled via comment and rulemaking rather than by guidance development.


A significant change made for the final guidance is the explicit promise that the FDA would not act on any information it deemed unreliable, unconfirmed, or not backed by sufficient strength of evidence. Industry may find itself flashing back to the drop in utilization of drug-eluting stents seen in 2006 and 2007 after disclosures regarding late-stent thrombosis at a medical society meeting in Barcelona, but the power morcellation question might be seen as a more obvious example of regulatory overreach with or without the help of physician input.

A second difference between the draft and final versions of the emerging signals guidance is that the latter discusses the formation of a group of subject-matter and regulatory experts charged with arriving at some understanding of the meaning of the initial signal. One of the options the agency could exercise is to require that the sponsor conduct additional postmarket studies of the device, while another option would be to suggest the manufacturer make a change to the device label. The exercise of this second option would presumably come up short of a removal of an indication for use, if only because a preliminary signal is not generally accorded sufficient weight to trigger a rescission of a 510(k) or a withdrawal of a PMA or PMA supplement.

More data, more need for compliance

An obvious subtext to the emerging signals guidance is the ongoing stand-up of the National Evaluation System for health Technology, known as NEST, which will take several years and several hundred million dollars to erect. The NEST system would presumably generate large volumes of data about device performance, but such a system might carry the signal-to-noise problem often seen in “big data” concepts. It is impossible for the FDA to guarantee it will not over-interpret a signal, particularly as it will undoubtedly be bombarded with allegations that the 21st Century Cures program will turn the FDA premarket programs into a series of rubber-stamp processes.

Perhaps now more than ever, device makers would do well to toe the line on the recent medical device reporting final guidance, if only to avoid pinging any patella tendons inside and outside the agency. Corrective and preventive action is still a big theme in warning letters, too, and any device maker that is seen as dropping the ball here will curry no favor with the FDA.

There is no guarantee the FDA will not overreact to an “emerging signal,” but companies can do a lot to keep investors and FDAers on their side – and to fend off would-be litigants – by running a tight regulatory ship.