Staking Claims: PTO Saving Patents, FDA Saving Lives

The world suffers no shortage of hyperbole, and sometimes those in the U.S. government get in on the act, too. Following are two stories of goverment agencies taking action in the month of May, with one agency easing up on a purportedly lethal administrative mechanism while the other asserts that its regulatory proposal would be quite the opposite of lethal.

PTO Revisits ‘Broadest Reasonable’ Standard

Those who saw the inter partes review process as an illegitimate shortcut to destruction of legitimate patents may have been cheered to see the U.S. Patent and Trademark Office declare that it would revisit its standard for interpreting claims that are the subject of an IPR, a welcome piece of news for patent holders.

Much of the criticism of the IPR process revolves around the notion that the process is a highly efficient patent-killing machine, and the use of broadest reasonable standard for interpreting the claims contested in an IPR was part of the problem. The difficulty for litigants was that matters appearing in an IPR or other PTO procedures might also be at play in the courts, thus setting up the prospect for differential outcomes due to PTO’s use of the broadest reasonable interpretation (BRI) standard.

Andrei Iancu, director of the PTO, said in remarks to a patent policy conference in April that the agency was taking a close look at various patent-related proceedings and the standards employed throughout those proceedings. The overall objective would be to increase the predictability of “appropriately scoped claims,” Iancu said, explaining that one of the agency’s tasks will be to close the gap between the prior art uncovered during the original patent examination and the prior art unearthed in litigation.

The PTO notice acknowledges that the BRI standard differs from the standards used in federal district courts and the International Trade Commission, and that nearly 87 percent of the patents caught up in proceedings instituted by the America Invents Act were also in play in the courts. This high rate of overlap, the agency said, suggests a need to use the same standard for claims interpretation. PTO also pointed to the outcome in the 2005 en banc hearing at the Federal Circuit for Phillips v. AWH Corp. as a stimulus to take a closer look at the viability of the BRI standard.

The agency said its views of the matter have also been shaped by a rethinking of the relative merits of extrinsic and intrinsic evidence. This portion of the PTO’s notice of proposed rulemaking states that the need to comport with Phillips means that the verbiage found in a claim will be interpreted by the “ordinary and customary meaning” of the words found in those claims. The PTO states that extrinsic evidence, such as expert testimony, may be useful, but not moreso than intrinsic evidence, and that the proposed rule would apply not only to IPR proceedings, but also to post-grant reviews and to proceedings for covered business method patents.

FDA Floats Life-Saving Combo Appeal process

The FDA has proposed to revise the process for appealing a determination regarding a combination product application, but the net effect of the proposed rule is anything but certain. One of the provisions of the proposed rule would eliminate what the agency characterized as a redundancy from the appeals process, but there are other feature of the proposed rule that invite closer scrutiny, such as the argument that one of the values of the rule is that it may save lives.

Up to now, the Part 3 appeals process for combination products has allowed a sponsor to appeal to the Office of Combination Products when the sponsor is unhappy with the OCP’s initial determination as to whether the product is primarily a drug, a device or a biologic. The FDA said it would delete section 3.8 from Part 3 altogether simply because appeals to the OCP cannot include information that was not part of the initial filing, and thus the outcome is likely to be unchanged. The notice also says that this part of the process led to some confusion regarding whether the sponsor can take the matter over the OCP’s head in the event of an adverse determination.

While the draft rule makes several claims on the subject of a net savings to industry after the first year, one of the more interesting observations on the part of the FDA is that if adopted, the rule would provide a public health benefit in the form of “illnesses and deaths avoided as a result of finalizing the proposed rule,” a curious observation to say the least. Conversely, one clear-cut benefit of the proposed rule is that it makes explicit that a sponsor need not contact the OCP if the product’s primary mode of action is clear.

One of the interesting parts of the rule in procedural terms is that only a sponsor would be allowed to file a request for designation for a particular combination of drug and device products. This would seem to foreclose any prospect of an industry collaboration, but another question in this context is whether the confidentiality of premarket submissions would disallow the disclosure of the status of a particular combination upon approval of that application.

Another proposed change to the regulation, yet another response to Section 3038 of the 21st Century Cures Act, is that the FDA would review a combination product under a single application when appropriate, although the Cures Act did not foreclose the possibility of a component-by-component review. As currently written, the regulation states that the agency can require that an application’s components be reviewed separately, but the FDA said it may simply delete this language from the regulation “to avoid confusion.”

The difficulty for regulated industries is that the FDA would only belatedly issue guidance or rulemaking as the agency’s staff gain experience implementing the changes imposed by the Cures Act. It might be assumed that the combination of legislatively imposed changes, and the proposal to excise language not directly required by that legislation, will in the near term engender more confusion rather than less.

April Showers: SCOTUS, FDA Spring into Action

Temperatures in our nation’s capital are returning to some vague sense of normalcy, which may or may not have anything to do with the normal functions of the Supreme Court and the FDA. Either way, both these entities have delivered some important news in the month of April, although it will be May or later before the related effects will make themselves felt. In the spirit of the vernal renewal of life, we offer the following.

Inter Partes Review Survives Challenge at SCOTUS

One of the most significant developments in the area of intellectual property in recent weeks was the Supreme Court decision in the case of Oil States Energy Services LLC v. Greene’s Energy Group LLC, which challenged the constitutionality of the inter partes review process. Had the Court decided in favor of Oil States, the IPR process would have been declared unconstitutional, thus bringing an end to one of the more controversial aspects of the America Invents Act (AIA).

The 7-2 opinion penned by Justice Clarence Thomas said that trials and other procedures addressing patent validity need not take place in an Article III court, but also that an IPR hearing does not violate the Seventh Amendment right to a jury trial. Thomas pointed to the ex parte reexamination of patents as an example of administrative proceedings that do not take place in a courtroom, a procedure that has been part of routine practice at the Patent and Trademark Office since 1980. He also cited the existence of the inter partes reexamination, which was replaced by the IPR process via the AIA.

Justice Neil Gorsuch wrote the dissenting opinion with the concurrence of Chief Justice John Roberts, stating that no courts other than federal courts were empowered to invalidate a patent until 1980. Gorsuch said the outcome does not “represent a rout, but it at least signals a retreat from Article III’s guarantees,” going on to argue that enforcement of Article III is principally about “ensuring that people today and tomorrow enjoy no fewer rights against governmental intrusion than those who came before.”

Gorsuch wrote the majority opinion in another IP case delivered on April 24, SAS v. Iancu, which held that the Patent Trial and Appeal Board must make a determination on each of the claims challenged by a petitioner in an IPR. In contrast to Oil States, this case squeaked by in a 5-4 vote, but the newest Supreme Court justice is definitely making his mark on the Court’s handling of patent law despite a lack of certainty on his views when he was appointed last year.

Gilead Up, Nargol Down at SCOTUS

We previously reported that two cases pertaining to the False Claims Act were the subjects of petitions for cert at the Supreme Court, and not unexpectedly, the Court passed on a chance to hear Medical Device Business Services, Inc. v. United States ex rel. Nargol. The Court said Justice Alito had taken no part in deciding whether to hear the case, although no explanation for that was given. The Court’s interest in Gilead v. Campie seems to have quickened, however, given that the justices have asked the Solicitor General to file a brief.

It may be too soon to speculate as to how the Trump administration would advise the Court regarding Gilead, but the 8-0 outcome in the Supreme Court’s review of Escobar would suggest that Solicitor General Noel Francisco has a limited amount of wiggle room for suggesting that the standard for materiality in False Claims Act cases ought to be relaxed. Conversely, however, federal attorneys are loathe to give up any leverage where FCA cases are concerned, and it might be pertinent to recall that the Thompson memo arose from an administration that might have been presumed to be less unfriendly to business than the administrations that preceded and followed.

In the end, the Solicitor General has the option to opine on nothing more than whether the Court should hear the case. The reader will hopefully excuse the cliché that this case “bears watching” as the Court will at the very least provide some additional clarity regarding the current standard for materiality.

FDA Issues First Inspection Report under FDARA

The legislation for the most recent series of FDA user fee agreements stipulated that the agency publish data on inspections for drugs and devices needed to approve that drug or device, and while the data are interesting, they are perhaps most useful as a baseline for evaluating the agency’s performance in this area over the next few years.

The report, which fulfills Section 902 of the Food and Drug Administration Reauthorization Act of 2017 (FDARA), covers calendar year 2017 only, not an unexpected limitation given the novelty of the requirement. The report states that for new drug and abbreviated new drug applications, the median elapsed time between the agency’s internal request for an inspection and the date of the inspection was 102 calendar days. Drug makers may be accustomed to such delays, but might not be happy with them all the same.

The median elapsed time for issuance of forms 483 for inspections with compliance issues was seven calendar days from the start of the inspection, and the agency pointed out that 483s are typically issued upon the close of the inspection. Perhaps more problematic is that 191 days on average passed between the date of the 483 and the date of any related warning letter, while any regulatory meetings to review the inspections on average took place 169 days later.

Ergo, the numbers suggest that a drug maker could end up waiting 300 days from the date of an internal FDA request for inspection to see a warning letter for that inspection, which sounds like a significant problem when trying to get a new drug to market. The report does not cover inspections related to biologics license applications, but does include data on inspections for supplemental drug filings.

The report states that FDA used the complete response (CR) letter to deny 94 new drug applications and supplemental filings for chemistry, manufacturing and controls in calendar 2017, a relatively small denominator in comparison to the more than 2,460 CR letters issued last year. However, the agency said it had issues another 194 facility-related CRs for a total of 288 facility-related CR letters in 2017, although there is little information on what sort of facility-related issues drove those additional 194 CRs. In any case, these numbers are likely to shift at least somewhat thanks to the concept-of-operations paradigm now in force at the Center for Drugs.

The dust-up between the FDA and device makers regarding inspection delays is well known – and the total number of original PMAs in any given year is presumably still fewer than 50 – so it’s no surprise that the numbers for device inspections differ significantly from those for drugs. The agency needed only a median of 35 days between the request for the inspection and the first day of that inspection, and the average time to issuance of a 483 was five days. As was the case for the drug inspection numbers, data pertaining to supplemental filings were included.

At first glance, it seems odd that Congress had included pre-clearance inspections for 510(k) applications in Section 902 if one takes the FDA at its word when it states that clearance of a device “does not require a pre-clearance inspection.” While the statement is sufficiently generic to be more or less defensible, it seems somewhat contradicted by the March 25, 2014, draft device classification rule, in which the agency acknowledged that it had conducted pre-clearance inspections for 510(k) applications, although it had done so only on “rare occasions.”

Three for 2018; New Year Off to a Fast Start

Those in the life science industries know better than to sleep on the courts and the FDA, and the first quarter of 2018 serves to nicely reinforce this lesson. Following are three stories of interest to drug and device makers, but while its clear that the outcomes of these developments are of tremendous importance, it is not at all clear where these three stories will land in the end.

Gilead Moves Closer to Cert 

One of the more notorious cases relating to the Federal Rules of Civil Procedure is Campie v. Gilead, but the Supreme Court will have at least two such cases to choose from thanks to a petition Medical Device Business Services, Inc. v. United States ex rel. Nargol. The problem for this latter case is that it seems to overlap with Gilead, and Gilead has been distributed for conference for April 13, suggesting that Nargol will for now stand as decided at the Court of Appeals for the First Circuit.

Gilead had petitioned for cert on Dec. 26, 2017, while Medical Device Business Services, once known as Nargol v. DePuy Orthopaedics Inc., completed its petition for cert Feb. 5 after requesting an extension in the first half of December 2017. MDBS v. Nargol takes up the issue of the Federal Rule of Civil Procedure 9(b), a dispute triggered by the fact that the two relators in this False Claims Act case never filed a billing claim for the purportedly violative device, and apparently do not even practice medicine in the U.S. The relators, who served as expert witnesses in a case against MDBS, built their claims largely around an extrapolation of one medical claim to all the billings for the company’s Pinnacle hip device, and the petitioner points to a split among the circuit courts as justification for a hearing at the Supreme Court.

Gilead Sciences Inc. petitioned for cert after the Ninth Circuit reversed a lower court’s dismissal of the case, which revolves around the use of an unapproved supplier of an active pharmaceutical ingredient. The company eventually cleared the new API source with the FDA, but not until two years after Gilead started doing business with the supplier. In this instance, the relators are former employers, and Gilead cites the Supreme Court decision Universal Health Services v. Escobar as a precedent, which MDBS does not. All in all, it seems likely that the Supreme Court will take Gilead if it takes either of these cases.

Intended Use Rule Back on Back Burner

The FDA’s intended use problem continues seemingly unabated with the announcement that the agency would suspend the intended use rule indefinitely pending a closer look at some of the underlying issues. The tobacco-related portions of the January 2017 final rule are unaffected, but the portions of the rule dealing with drugs and devices are once again in regulatory limbo. The agency said it has in the meantime reverted to the previous understanding of the question of intended use.

The Federal Register notice regarding this indefinite suspension states that some had criticized the inclusion of the totality-of-evidence standard seen in the January 2017 final rule, principally because that standard had not appeared in the 2015 draft and thus its introduction in the final rule violated the Administrative Procedures Act. While there are a number of other issues raised by stakeholders, the totality-of-evidence standards was perhaps the most contentious, and if anything can be said about the FDA’s current predicament, it’s that the agency cannot afford to sit on this issue indefinitely because some states are moving ahead with their own laws pertaining to commercial speech, federal preemption notwithstanding. Those in the life science industries will want to stay tuned.

Least Burdensome Draft Draws Fire

The docket for the latest draft guidance for the FDA’s least burdensome standard has closed, but a number of observers are quite skeptical as to whether the agency means what it says about the principle of least burdensome.

The FDA’s Center for Devices and Radiological Health released the latest draft guidance at the end of 2017, acknowledging at the outset that the standard was encoded in the statute in 1997 via the Food and Drug Administration Modernization Act. Two subsequent pieces of legislation, including the 21st Century Cures Act, also applied pressure on the agency to formalize the least burdensome standard. Nonetheless, Jeffrey Gibbs of Hyman, Phelps & McNamara said in comments to the docket that the agency has engaged in “boilerplate recitation” of the standard without actually following through.

Gibbs charged that experience has repeatedly shown that the agency has inconsistently, at best, applied the least burdensome standard in a range premarket filings, including 510(k) and PMA submissions. He argued that the agency’s reviewers have routinely failed to explain the need for data beyond that used to clear a predicate device in the case of 510(k) submissions, and similar devices in the context of PMA applications.

Gibbs urged the agency to offer applicants a conference call within five days of the issuance of a request for additional information for premarket filings, a proposal he said builds off a pilot program that offers applicants “a short teleconference” within 10 days of the request. He said this pilot offers only about 15 minutes of teleconference time with the application’s reviewers, an amount of time he suggested is inadequate.

The Medical Imaging & Technology Alliance said the draft invoked the question of medical necessity when the agency has to consider what sort of least burdensome enforcement action is needed to deal with violative devices. MITA’s executive director, Patrick Hope, countered that medical necessity is a standard for payers to determine, and that the association is “concerned about the potential for scope creep” should the medical necessity question play a role in the agency’s decisions.

FDA’s Intended Use Rule Back in Play

A number of regulatory and enforcement items have been up for grabs at the FDA over the past year, but few carry the weight of the agency’s review of the intended use rule. The FDA announced recently that it is suspending the implementation date for the rule, and is separating the tobacco-related portions of the rule from those governing drugs and devices. It’s a welcome step and one that is long overdue, but it is not clear yet where the agency will land on this matter.

Dexcom Warning Letter Pulled

To recap, this problem dates back to at least 2011, when Par Pharmaceutical Inc. sued the agency over the latter’s attempts to suppress Par’s on-label discussion of the company’s appetite stimulant, Megace ES, in a setting in which the drug was likely to be used off-label. Par agreed to pay a $45 million fine two years later, and the five-year corporate integrity agreement is finally set to expire later this year.

Glucose monitor maker Dexcom subsequently received an FDA warning letter alleging the device maker was aware that its devices had been sold for uses that fell outside the labeled indication, but the agency has since deleted that document from the warning letter database. The agency took an explicit approach to the issue in a Federal Register announcement in September 2015, a peculiar attempt to devise a rule that would cover tobacco products along with drugs, devices and biologics. The FDA said its intent was to clarify some of the related issues, but the 10-page draft included the curious observation that a lack of clarity might lead consumers to use tobacco products “in place of FDA-approved medical products.”

The final rule appeared in early 2017 and retained the plus-tobacco features of the proposed rule, but the document grew to 25 pages and included a more or less lengthy discussion of the Central Hudson test and other issues that came up in comments to the docket. However, the agency then delayed implementation of the final rule to March 21, 2017, and then to March 19, 2018, and FDA commissioner Scott Gottlieb said in the agency’s Jan. 12 statement that the final rule will be suspended yet again “until further notice.”

A Procession of Concessions Fails

The 2015 proposed rule rattled observers by stating that the agency’s determination of a product’s intended use “is not bound by” explicit claims made by the manufacturer, but can instead be inferred by “objective evidence,” including the circumstances “surrounding the distribution of the product or the context in which it is sold.” The FDA tried to assuage industry’s concerns by vowing that it would not act on distribution of a product “based solely on a firm’s knowledge” of off-label use, but this concession did little to mollify industry.

The agency took a somewhat different approach in the final rule, stating that “a totality of the evidence” would be employed to determine an intent to knowingly distribute a drug or device for off-label uses. However, the Advanced Medical Technology Association argued that an approach based on the totality of the evidence is “more outcome determinative than prescriptive,” and thus manufacturers would have little choice but to “curb important product-related communications.”

The intended use rule does not entirely capture the regulated speech problem, but it is a significant hazard, particularly since whistleblowers and the Department of Justice can readily avail themselves of fodder for prosecution. It is pertinent to note that the Par Pharma case involved multiple relators, who had netted more than $4 million when all was said and done.

States Moving Ahead

There are several questions looming for the FDA, but whether the agency is in a position to stand pat is not one of those questions. The State of Arizona passed a law last year that takes up the off-label communication issue, and there are indications that other states may soon follow suit. Gottlieb has already noted that the FDA must come to grips with recent jurisprudence on the off-label issue, and the agency can scarcely afford to be swamped by a pixelated map of state policymaking where commercial speech is concerned.

The easy answer to all this is that Gottlieb will scuttle the totality-of-evidence standard, but little beyond that is especially obvious. The FDA said it will take comment through Feb. 5 on this latest iteration of the intended use scrum, so there is still time to weigh in. Given that the docket for this issue already features nearly 2,000 comments, it’s clear that significant change is in the works.

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.

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.

Changes; Azar at Senate HELP and the 510(k) Dilemma

Change is constant, but some changes are easier to manage than others. The change at the office of Secretary of Health and Human Services has been a while in coming, but promises to spark partisanship on Capitol Hill. The FDA approach to changes to 510(k) medical devices, however, seem likely to provoke less anxiety than has been the case in times gone by.

Hearing Foreshadows Road Ahead for Azar

Alex Azar, the Trump administration’s nominee for the Secretary of Health and Human Services, went through the usual hazing at a hearing of the Senate Health, Education, Labor and Pensions Committee on Nov. 29, but this was a non-voting hearing. Still, the hearing gave some indication of what is likely to follow in the days ahead as the former drug company executive goes through the Senate vetting process.

Azar had served at HHS during the second Bush administration, but then was the president of a division of Eli Lilly that was involved in a doubling of the list price for Humalog, an insulin analogue. That issue arose during the hearing, but Azar said the system allows for that kind of gaming while vowing to put an end to such practices. Democrats on the panel were not persuaded, but Republicans were not critical of Azar’s past, highlighting partisan tensions that are sure to persist.

The next stop for Azar is the Senate Finance Committee, which will hold a vote at some point on Azar, but there is a substantial amount of overlap in the HELP and Finance Committee’s memberships. The fireworks are sure to increase, and this is almost certain to go down to a party-line vote in both the Finance Committee and the Senate floor.

510(k) Changes Guidances Tweaked from Drafts

The FDA’s device center finalized the guidances dealing with changes to class II devices and changes to software devices, and while the tenor of the final guidances is similar to that found in the drafts, there are a few important differences in each. One might recall, though, that the 2011 effort to rewrite the legacy K97 guidance was possessed of a much different animus, so much so that Congress forced the FDA to withdraw that attempt.

The agency held a webinar in November for these two guidances, during which members of the FDA staff said that changes to a 510(k) draft’s user interface might not require a new filing, even if that alteration merits a fresh human factors engineering examination. The final 510(k) changes guidance offers considerably more detail where labeling changes are concerned, most of which is found in a flowchart that poses questions as to the nature of the change. The additional detail should go a long way toward allowing a device maker to establish whether a labeling change will call for a new filing.

However, anyone who was looking for a shift in the discussion regarding changes to materials or to technology and performance may be disappointed to see that the final nearly replicates the language found in the draft. Still, the draft version made a concession that carries over into the final in that the withdrawal of an indication for use will not automatically call for a new regulatory filing.

Where the software 510(k) guidance is concerned, FDAers said a change of operating systems would not likely force a new filing so long as that change is within the same family of operating systems. Migrating the software device from one platform to another, however, is likely to introduce sufficient questions about the attendant functional hazards to require a new 510(k) demonstrating that the sponsor has those hazards well controlled.

One seemingly important difference between the software draft and the final is that the latter suggests that a new filing will be needed if a change to the software requires the use of new risk controls, even in instances in which those controls address an existing and known hazard.

Those who are looking for additional clarity surrounding the meaning of the term “significant risk” in connection with changes are likely to be disappointed. The significant risk dilemma is present in both guidances, but FDA staff on the conference call indicated that the agency believes that some flexibility on its part – which comes across to sponsors as uncertainty – is called for in dealing with its regulatory oversight of these devices.