PTO Seeking Comment on AI as Patent Owner, Inventor

The U.S. Patent and Trademark Office still has its hands full over the question of the Supreme Court’s views on life science patents, but the agency must now begin to grapple with an entirely new set of dilemmas. PTO recently announced it is seeking feedback on the status of artificial intelligence (AI) as an inventor and as a patent owner, two questions that may defy answer in the near term.

U.K. Researchers Argue for Change

Researchers at the University of Surrey in Surrey, U.K., announced at the beginning of August that they had filed for patent protection for two inventions autonomously created by an algorithm known as DABUS. The inventions are for relatively simple products – one is a beverage container with a design based on fractal geometry, while the other is a device for attracting the attention of would-be rescuers – but the team at Surrey has applied for patents for these items in the patent offices for the U.K., the U.S., and the European Union.

According to the statement, the U.K. Intellectual Property Office has already concluded that the inventions pass the preliminary test for inventiveness, although the agency has not yet taken up the question of whether non-human entities can be cited as an inventor. So far, this is as much as the researchers at Surrey are asking the agency to consider.

Ryan Abbott of the University of Surrey School of Law said in the statement, “there would be no question the AI was the only inventor if it was a natural person,” and argued that DABUS should be listed as an inventor. Abbott said developers of an algorithm should be designated the assignee or owner of any patents produced by that algorithm, arguing that such an outcome would reward innovation and “keep the patent system focused on promoting invention by encouraging the development of inventive AI, rather than on creating obstacles.”

The question is not an entirely novel one as indicated by a discussion of the question in a law journal last year, but the difficulty for patent offices is that the statutes under which these agencies work seem to leave them with little leeway. The statute in the U.S. states that a patent can be awarded to “whoever” invents something useful, while the law in the U.K. make reference to “persons” as inventors. Thus much of the debate is likely to center on a need for legislation.

PTO Broaches Ownership Question

The American patent office announced Aug. 27 that it seeks feedback on whether further guidance from the agency is needed to “promote the reliability and predictability” of patent applications filed on behalf of AI. PTO also poses the question of whether new forms of patent protection are needed, adding that some of the issues surrounding software inventions are relevant for the discussion of AI patents.

There is a need for clarity regarding terminology as the PTO noted that the term “AI inventions” is used to denote both inventions that utilize AI and those that are developed by AI. PTO also is inquiring into the circumstances in which humans might be designated co-inventor with the algorithm, as well as whether the laws and regulations are in need of revision to address the question of inventorship.

However, PTO went further, asking whether an algorithm can and should be allowed to be designated the owner of the invention. As intractable as such a problem may be, some of the more prosaic questions are likely to prove challenging as well, such as whether a change is needed in the written description requirement regarding the level of detail provided about the algorithm. PTO noted that this question could prove difficult to answer, given that some deep learning systems may have layers of functions that are obscured, and that some functions may evolve without human assistance or intervention. PTO is taking comment through Oct. 11, but it seems likely that the debate over AI inventorship and ownership has only just begun.

Controversies in Limbo: Paclitaxel and the Lab Rate Reset

Occupants of the med tech industry are all too aware that the issues that affect their livelihoods often take quite a while to play out, a fact of life that can permanently damage a manufacturer’s fortunes. Following are two such episodes, one involving the paclitaxel problem for devices used in the femoropopliteal arteries and the other a scrum arising from a congressionally mandated reset of the Medicare clinical lab fee schedule.

Uncertainty Persists After Latest FDA Update on Paclitaxel

The controversy over the use of paclitaxel in drug-eluting balloons and drug-eluting stents for the lower limbs seems no closer to a resolution after the FDA posted a new update on the matter. The emphasis now is on consent and labeling, the agency said, but the question of whether the presumed mortality signal related to these devices is little closer, if any, to resolution than it was at the beginning of the year.

The FDA’s Jan. 17, 2019, letter to physicians made reference to the medical journal article alleging that a higher mortality rate was seen in DCB and DES devices using paclitaxel as an antiproliferative, an association that began to emerge in some data sets at about two years. The agency held a two-day advisory hearing on the question during which several prominent cardiologists said the purported connection between paclitaxel and mortality compared to uncoated balloons and stents was poorly backed by the evidence. One clinician, Renu Virmani of the CVPath Institute in Gaithersburg, Md., said she had conducted more than 100 autopsies of patients who had been treated with paclitaxel-bearing devices in the coronary arteries and that none of those deaths were due to the antiproliferative. Virmani, whose remarks can be seen in the FDA transcript for the second day of the hearing, said those fatalities were instead caused by the patient’s underlying coronary artery disease.

The agency’s latest update, posted Aug. 7, is aimed at health care professionals, but the agency stated it is working with device makers and researchers on adding to the evidence base. At present, that evidence includes three randomized trials which enrolled slightly fewer than 1,100 patients, and the agency said the crude mortality rate at five years for these studies was nearly 20 percent for paclitaxel-coated devices and 12.7 percent with uncoated devices. This translates into a 57 percent increase in mortality risk, but the FDA also noted that a meta-analysis performed by Vascular InterVentional Advances Physicians on patient-level data arrived at a hazard ratio of 1.38. This analysis, the FDA said, was based on data provided by manufacturers.

The effect on device makers has been noticeable, with one device maker stating on an investor conference call that sales of their DCB device were cut by 50 percent, while another company lost out on a Medicare new technology add-on payment because of the association between paclitaxel and mortality. Despite the impact on utilization and thus sales, the FDA has acknowledged that there is no apparent connection between dose and mortality, and that there is as yet no demonstrated mechanism of causation.

The FDA announcement advised clinicians that the benefits of these devices may outweigh the risks for patients at “particularly high risk” of restenosis and repeat procedures to deal with the underlying disease. Sponsors of ongoing studies will likely have to amend their informed consent documents, which along with the media coverage could hamper trial enrollment and completion.

Appeals Court Sides with ACLA in Lab Rate Lawsuit

The Protecting Access to Medicare Act of 2014 called on the Centers for Medicare & Medicaid Services to reset the rates paid for lab tests by surveying labs for the rates paid by private payers, but the agency’s efforts to comply with that mandate were mired in controversy nearly from the outset. The American Clinical Laboratory Association filed a lawsuit against the agency in the U.S. District Court for the District of Columbia, but lost in that suit, although an appeals court recently overturned that dismissal.

The D.C. District Court dismissed the lawsuit in September 2018 due to a purported lack of subject matter jurisdiction, but the U.S. Court of Appeals for the District of Columbia reversed that finding in part. The appeals court said that while the rates provided by Medicare under the clinical lab fee schedule are not subject to judicial review, PAMA did not clearly provide that insulation from legal challenge to the methods used by CMS to collect the private payer data.

There is legislation in the House of Representatives that would suspend the rate reset effort another year, and would require that the National Academy of Medicine advise CMS on the question of sampling. The Laboratory Access for Beneficiaries Act of 2019 (H.R. 3584) was introduced to the House Ways and Means and Energy and Commerce Committees in June, but has the support of only 13 sponsors as of Aug. 11. There does not appear to be a companion bill in the Senate, either, according to the bill’s listing at Congress.gov. ACLA said in a July 30 statement that the D.C. District Court should “act quickly” to respond to the appeals court decision, but also that Congress should “immediately halt the data reporting process.”

Supreme Court, DOJ Revisit False Claims Act

The False Claims Act might be the most widely known tool in the Department of Justice’s enforcement toolkit, and the FCA was in the news twice in the month of May. As the saying goes, there is some good news and some bad news, but these are both developments to which those in the life sciences should pay close attention.

Statute of Limitations Expanded

Starting with the bad news, the U.S. Supreme Court handed down a 9-0 decision in Cochise Consultancy Inc. v. United States, ex rel. Hunt, the net effect of which was to give relators an additional three years to file a qui tam action before the statute of limitations closes the door. Cochise revolved around a contract with the U.S. Department of Defense, and the interpretation of the statute of limitations had varied among the U.S. circuit courts, thus the Supreme Court’s interest in the case.

The statute was generally interpreted as giving relators six years to file a whistleblower lawsuit, or within three years of the time that a federal government official knew or should have known about the alleged wrongdoing. That additional three-year window for relators was widely assumed to be predicated on the federal government’s intervention in the case, however. A district court dismissed the relator’s case, but the Eleventh Circuit reversed the lower court’s findings. The relator, Billy Joe Hunt, filed his action more than six years after the alleged wrongdoing, but within three years of his disclosure of the events in question to the FBI, although the U.S. federal government never intervened.

The U.S. Solicitor General supported the relator with an amicus brief stating that the text of the statute makes no distinction between qui tam suits in which the federal government does or does not intervene, a view affirmed by Justice Clarence Thomas, who penned the May 13 opinion. There are some potentially far-reaching implications for the life sciences, given that some FCA actions involve recurring claims filed with Medicare. A question Justice Thomas did not answer hinges on the statute’s language pointing to the scope of the FCA, which cites federal officials who are “charged with responsibility to act in the circumstances.” This would seem to be a pertinent question for Cochise, given that the relator in this case, Billy Joe Hunt, had discussed his findings with the FBI, not the Department of Defense, which presumably would have had oversight of defense contracts. These and other questions have been left for another day.

New DOJ policy Overwrites Yates Memo

Earlier in the month of May, DOJ announced a new policy regarding credit for cooperation for corporate defendants in FCA cases, a question that has been very topical for the department at least since 2003, the year of the Thompson memo. The tone of this latest announcement is much less stringent than might have been issued in connection with the now-famed Yates memo, but one of the more interesting passages suggests the department might be willing to eliminate a relator lawsuit in order to clear out an FCA case.

The new policy, credited to assistant attorney general Jody Hunt, provides corporate defendants with partial credit for any of three actions, including the implementation of remedial measures designed to prevent illicit conduct in the future. Hunt also said defendants can earn cooperation credit by preserving relevant documents beyond that which would be required by conventional business practices or legal requirements, which suggests companies in the life sciences may already be revisiting their record retention policies.

Beyond all this, the DOJ statement indicates that cooperation credit will “most frequently” be expressed as reduction in civil penalties and damages multipliers. However, the most interesting part of this development is seen only in the amended version of the Justice Manual, which now includes the statement that cooperation credit might avail the defendant of the DOJ’s assistance “in resolving qui tam litigation with a relator or relators.”

As is widely known, the Granston memo suggested the DOJ would be more likely to dismiss relator litigation when that litigation would interfere with other federal agencies’ efforts to fulfill their policies, but this change to the Justice Manual seems to take the Granston memo a step further in an effort to reward certain behaviors. How frequently the department would see fit to dismiss a qui tam in order to create inducements for other defendants to be more forthcoming is impossible to predict, but the frequency with which the FCA is invoked suggests observers might not have to wait very long at all to see this policy in action.

Paclitaxel Focus of Device Controversy

The technology behind percutaneous treatment for the coronary arteries has advanced much more rapidly than for the peripheral vasculature, but the use of paclitaxel, a chemotherapeutic agent, as a go-to antiproliferative for any part of the anatomy could be near an end. The FDA published a letter to physicians in January stating that a medical journal article suggested that paclitaxel-bearing drug-eluting stents (DESs) and drug-coated balloons (DCBs) for the peripheral arteries had demonstrated an unexpectedly high long-term mortality rate compared to bare-metal stents and non-coated balloons. However, the conclusions drawn in that medical journal are the subject of a dispute that may determine whether paclitaxel has any future at all in the circulatory system.

The article in the Journal of the American Heart Association describes a meta-analysis covering more than two dozen randomized, controlled trials for both DES and DCB devices, all coated with paclitaxel. The authors stated that all-cause death at both two and five years for paclitaxel devices was significantly higher than for their non-eluting counterparts when used in the arteries of the lower extremities, but that more study is warranted, in part because only two of those studies ran for a full five years. The authors hypothesize that the crystalline form of paclitaxel, which has a longer half-life than other formulations, may be the culprit.

Medtronic, the Dublin-based manufacturer of the In.Pact Admiral DCB, took issue with the JAHA authors in an article in the Journal of the American College of Cardiology, stating that there is no statistically significant difference in mortality between DCBs and plain angioplasty balloons at five years. As is the case with the JAHA analysis, there are a number of moving parts in the Medtronic summary, including that the data are drawn from patients in a variety of nations that exhibit different patterns of post-procedural care, not to mention differences in the use of dual anti-platelet therapy (DAPT). The company argued that much of the difference in mortality outcomes could hinge on the more aggressive use of DAPT in patients treated with bare-metal stents and plain angioplasty balloons.

Whether any of this clinical data will translate into regulatory action is impossible to forecast, but the FDA advised that it still sees the benefit of these devices as outweighing the risks. If Medtronic’s view – that the mortality rates at five years out, at least in statistical terms – wins the day, device makers might be on the hook for nothing more than a somewhat greater post-market surveillance liability. Makers of DCBs might already be on that track, as the Centers for Medicare & Medicaid Services (CMS) declared it will pay what clinicians and device makers see as a sub-optimal rate for these devices, unless and until CMS sees some compelling data that the difference in cost between DCBs and plain balloons is justified by outcomes.

E.U. Regulators Tackle Big Data, Definitions

Data may save lots of lives over the course of the 21st century, but the volume of data has created a number of headaches for regulators and life science companies alike. In response, two European regulatory entities have teamed up to take on these vital questions, and their report suggests it was no trivial matter just deciding upon a definition of the term “big data.”

The European Medicines Authority (EMA) and the Heads of Medicines Agency (HMA), the latter of which is a group of E.U. competent authorities, posted the report on the activities of the HMA/EMA Joint Big Data Task Force. The group formed six working groups to consider the data derived from a number of sources, such as genomics and clinical trial data, and set certain standards for regulatory acceptability of those data. Data standardization is a matter of some interest, as is the ages-old problem of data sharing.

The report states that there is an emphasis on providing some linkage between genomic data and clinical outcomes, but the authors say this will create pressure to provide timely updates of clinically relevant genomic information in medicinal product labels. There is also a keen interest, however, in defining performance standards for companion diagnostics, an ever-more pressing consideration as highly expensive cancer therapies continue to find their way to market.

The report includes information from a survey of stakeholders regarding their familiarity with big data, and it appears a number of the competent authorities in the survey enjoy “very limited expertise” on the subject. This lack of expertise is due to a perception that there is little need for it at present, but this dynamic is changing. Eight of the 24 competent authorities surveyed said they have no in-house expertise in biostatistics, but indicated they see a need for such expertise arising within the next five years; the study authors pointed out that such assets are already a necessity.

A total of 37 life sciences companies responded to the survey, with the group nearly evenly split between companies with more than 250 employees and those with 250 or fewer. This dividing line yielded quite different sets of considerations, with the larger companies expecting that big data will have the most significant impact on target identification and patient stratification, while their smaller counterparts emphasize outcome identification and patient-reported outcomes.

The two groups also had different concerns regarding data validity and the challenges associated with the use of big data, but shared concerns regarding regulatory harmonization and a need for regulatory guidance. The report concludes that the ability to manage big data will, in the future, be critical for the advance of regulatory science, but the authors also pointed to a need for a “systemic, coordinated, and integrated European approach” to such questions. While good intentions will prove vital to any such effort, the authors say that there is still a need to prioritize the various tasks of learning to manage and use big data, and that the current effort is moving along “in the right direction but not in a consistent and consolidated way.” The authors stated, “[W]e therefore need to guard against reverting to the status quo.” Comments on the joint task force report are due April 15.

BIO, PhRMA Not Opposed to AKS Proposal

Makers of drugs and biotech therapeutics might have been expected to resist the Trump administration’s proposal regarding the anti-kickback statute, but that proves not to be the case. Two leading trade associations have voiced their support for the proposal, although they each indicated they would take a closer look at the proposal before lending it their full-throated support.

It has been argued on more than one occasion that rebates paid to pharmaceutical benefits managers are rebates rather than kickbacks, a point made by at least one observer. There have been instances in which drug makers paid fines to deal with allegations they used rebates to gain exclusive listings in PBM formularies, but that is not the usual run of business where these rebates to PBMs are concerned.

The latest proposal by the Department of Health and Human Services includes a removal of the safe harbor for rebates paid to several entities, including PBMs, although PBM service fees would enjoy a safe harbor along with rebates provided directly to beneficiaries enrolled in federal government health programs. HHS Secretary Alex Azar said in a statement the proposal is “a major departure from a broken status quo that serves special interests,” and which “moves toward a new system that puts American patients first.” The proposal would further provide more transparency about such transactions, and Azar seemed to taunt Congress on this point, stating that members of both parties who have sought to lower prescription drug costs “have criticized this opaque system for years, and they could pass our proposal into law immediately.”

Despite the seeming promise of disruption of the existing system, both the Biotechnology Innovation Organization and the Pharmaceutical Research and Manufacturers of America issued statements that were generally supportive of the proposal. BIO President/CEO Jim Greenwood said in a Jan. 31 statement that the association “strongly supports the goal” of the proposal, but advised that BIO is taking a close look at the proposal. Greenwood said the current system creates some perverse incentives that feed the drug pricing problem, urging HHS to adopt a system that provides affordable access.

PhRMA emphasized a need to ensure that the $150 billion in annual rebates and discounts are used to lower costs for patients at the pharmacy. PhRMA President/CEO Steve Ubl stated that the existing approach favors products with high list prices, but he also pointed to the pressing problem of price hikes associated with drug products used for diabetes, which has been a significant flashpoint in recent months. Despite the supportive tone, Ubl said PhRMA would also take a close look at the proposal before offering specific comments.

FDA Rewrites Title of Abbreviated 510(k) Draft

The FDA’s device center managed to wrap up a 2018 draft guidance dealing with abbreviated 510(k) applications, but ended up renaming the document in the process. The net effect is seemingly to put another nail in the substantial equivalence coffin, which some might argue has been a policy priority for the Center for Devices and Radiological Health dating back to 2011.

The 2018 draft guidance bore a title that explicitly mentioned the abbreviated 510(k) program and suggested that a determination of substantial equivalence would be more easily obtained by demonstrating conformance with performance criteria. The final guidance is dubbed the Safety and Performance-Based Pathway, which advises that third party reviewers can be invoked for these devices, which was not acknowledged in the draft.

One of the more notable differences between the draft and the final is that the latter suggests that the performance criteria requirements for Declarations of Conformity might be more explicitly product-specific than perhaps was understood upon the emergence of the draft. The final guidance says a DoC ought to suffice to support a finding of substantial equivalence “unless noted otherwise in the relevant Safety and Performance Based Pathway guidance.” While there is a seemingly related provision in the draft – which states that the FDA may “establish performance criteria through guidance and/or special controls” – the revision appearing in the final seems to lend more teeth to the notion that at least some procodes will be the subjects of product-specific performance criteria.

Precisely when the agency might promulgate such guidance is not explained, but the implications of this and other recent policy changes at CDRH include that the historical understanding of the role of substantial equivalence is no longer in vogue at the Office of Device Evaluation. Only time will tell whether reviewers at ODE can resist the urge to use performance criteria as a means of imposing more regulatory hurdles for class II devices

A Look Ahead to 2019

2018 was anything but a slow year for regulatory developments in the world of medical technology, but there is still plenty to look forward to for 2019. Following are several key developments that will do much to shape the prospects for industry going forward.

Rules of Civil Procedure Revised

This first item is not an FDA regulatory matter, but refers to something that took place in early December 2018, although the real impact is unlikely to be felt until 2019 starts to unwind. The Advisory Committee on Civil Rules had amended several of the Federal Rules of Civil Procedure earlier in the year, and those changes, including those applied to Rule 23, went into force Dec. 1.

One of the changes to Rule 23 allows the use of one or more electronic methods of contacting members of a class action regarding settlements, but a more significant change is in the method for dealing with bad objectors. Up to Dec. 1, a court had to approve the withdrawal of each individual objection to a settlement, but that requirement is no longer in force. Those whose objections are seen as an impediment to a reasonable settlement can simply withdraw their objections without forcing the court through a time-consuming review of the objection. While there are other issues related to the Federal Rules of Civil Procedure that are in need of redress, these latest changes should at least expedite the process considerably.

Device Tax Again Topical

Despite that it is not scheduled to resume until after 2019, the 2.3 percent tax on medical devices is again in the news thanks to the prospect that it might be pushed back an additional five years. That is the stated intent in connection with legislation that would provide some fixes for the tax overhaul signed into law at the end of 2017.

That legislation, which arose from the House Ways and Means Committee, seems to have been pushed aside by the latest budget impasse, however, although the fact that the tax does not resume for another year should give industry some comfort. Device makers will argue that their budgeting for activities such as research and development require more than a 12-month window, but it is not at all clear whether House Democrats are interested in H.R. 88 as currently written, if at all. Consequently, it seems at least somewhat likely that the device tax suspension will once again come down to the 11th hour.

As an aside, the budget problem involves the FDA budget, and one line of thinking is that the stand-off between the White House and Capitol Hill has better odds of resolution once the 116th Congress is sworn in on Jan. 3. In the meantime, user fees are funding much of the agency’s work, but routine manufacturing facility inspections may be held up in the meantime.

FDA’s Clinical Lab Regulation

This issue has been percolating for several years now, and includes an FDA discussion paper published in early 2017. That effort has been supplanted by a “technical assistance” provided to Congress in August 2018.

The original impetus for the FDA’s technical assistance was to help Congress refine the Diagnostic Accuracy and Innovation Act, but that bill has given way to the Verifying Accurate Leading-edge IVCT Development Act of 2018. Both bills were primarily sponsored by Reps. Diana DeGette (D-Colo.) and Larry Bucshon (R-Ind.) although the VALID Act is still in the form of a discussion draft, according to DeGette’s congressional webpage.

The bill makes reference to a precertification concept similar to that seen in digital health, which would be applied to moderate-risk tests, while high-risk tests would still be subject to the more traditional premarket review processes. Other interested parties include Sen. Orrin Hatch (R-Utah), who said in a statement that supporters will push the bill in the 116th Congress, suggesting that 2019 might finally be the year that the agency’s clunky approach to diagnostics regulation will receive a much-needed overhaul.

Guidance Agenda for 2019

The FDA’s device center is always busily compiling a new round of guidances, but one of the priority guidances of interest as announced in the device guidance agenda is a draft for demonstrating substantial equivalence through the use of performance criteria. This draft will pertain to abbreviated 510(k)s, according to the CDRH guidance agenda, but this draft might be as important as any that will emerge in this new year, thanks in part to what some observers are likely to see as an end run around the statute. The agency announced it would revisit the 510(k) program in an November announcement which also evinced some hostility toward the substantial equivalence standard.

There are a number of existing guidances that may be up for review as well, including the 1999 guidance for surgical mesh 510(k)s. That document is on the agenda for the obvious reason, including that the agency has up-classified these meshes for at least one indication, not to mention the ongoing patient concerns about mesh implants that have gone bad.

Barrage of Adverse Event Coverage Hits Device Industry

The International Consortium of Investigative Journalists has taken aim at the medical device industry with a series of articles on device recalls and adverse events, a series that has not gone unnoticed among device makers. The initial question for device makers is whether these reports will affect how regulatory authorities review devices, but it appears that at least one regulatory entity has acted on the report with a call for tighter premarket scrutiny.

The ICIJ, a 200-plus member watchdog group founded in 1997 by the Center for Public Integrity, has previously published on tax havens in the 2015 report titled the Panama Papers. The latest set of reports, the Implant Files, focuses principally on medium- and high-risk implanted medical devices, taking on subjects such as breast implants and transcatheter aortic valves, but the organization also picked out Dublin-based Medtronic for a report on alleged abuses.

Yet another report takes on the device regulatory picture in the European Union, which is still implementing the Medical Device Regulations that will not be fully in force for another two years for non-diagnostic medical devices. One of the difficulties of the data unearthed by the ICIJ is that there is no denominator for the increase in the total number of medical devices in use over the past few years, but the reports also suffer from the long-standing problem of the absence of information that clarifies whether the adverse event was principally or entirely the fault of a malfunctioning device.

Health Canada Among the First to React

Despite the concerns regarding the difficulty of interpreting raw adverse event data, the reaction among regulators has been fairly swift. Health Canada posted a Nov. 29 statement from Ginette Petitpas Taylor, Canada’s Minister of Health, who said she was “deeply concerned” by the Implant Files coverage, although she said that Canada “has one of the best regulatory systems in the world for medical devices.”

Nonetheless, Taylor said she had directed Health Canada to draft a plan that would, among other things, amend the premarket review process to require more clinical data for medical devices. Health Canada will also increase its capacity for medical device inspections and bolster its postmarket surveillance capacity, while greater transparency for medium-high and high-risk devices is also on the agenda. Taylor said the agency will publish its response “in the coming weeks.”

The reaction in Western Europe has come from a number of sources and includes a claim on the ICIJ website that the health ministers for Denmark and Italy have vowed to take action despite that the MDR overhaul is still in the works. Stakeholders in several nations have reacted to the news with calls for tighter government scrutiny, including the U.K. Royal College of Surgeons, which urged the Medicines and Health Care Products Regulatory Agency to implement an exhaustive registry for all implanted devices. MHRA has not declared how it will deal with regulations after the Brexit, which itself is not scheduled to go into force until early 2019.

For its part, the FDA has responded to media inquiries by stating that it is limited in its ability to rapidly access data for adverse events, a predicament that the National Evaluation System for health Technology (NEST) is designed to resolve. However, the FDA also announced several moves in conjunction with its medical device safety initiative earlier this year.

In its latest announcement, the agency said it is considering a ban on the use of predicates older than 10 years in 510(k) filings, along with measures that would more or less put an end to the use of the substantial equivalence paradigm. All this is drawing fire from the regulatory bar, some members of which have voiced the view that these proposals might require more than mere consultation with Congress. The agency is not stating whether these latest proposals were prompted by the ICIJ report, but the timing is difficult to ignore, particularly given the seeming improbability that it will be able to implement some of the more far-reaching of those proposals.

Supreme Court Cases to Watch This Term

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

This term (which began last month), the Supreme Court will hear a number of cases that may affect the life sciences industry. Here are a few we will be watching.

Air and Liquid Systems Corp. v. DeVries

The issue in this case is whether defendants in a products liability case can be held liable under maritime law for injuries caused by products they did not make, sell, or distribute. The Court heard argument in this case on October 10. The case involves equipment sold by various manufacturers and installed several years ago on Navy ships. To function properly, the equipment required asbestos insulation, which was installed shortly after equipment. The plaintiffs are a group of individuals who worked on the ships at the time and were allegedly injured by the asbestos.

Merck Sharp & Dohme Corp. v. Albrecht

This is another preemption case, and an important one for makers of drugs and, potentially, PMA devices. The issue here is whether a plaintiff’s state-law-based failure-to-warn claim is preempted if the FDA rejected the drug manufacturer’s proposal to warn about the specific risk the state-law claim alleges should have been warned about. Argument has not been scheduled in this case yet.

Senators Inquire into FDA Digital Precert

The FDA precertification program for digital health has raised eyebrows across the industrial spectrum on several points, but the program has now caught the attention of three members of the U.S. Senate. An Oct. 10 letter from the trio, a document spanning a dozen pages, pokes at the agency on a number of issues, including the question of whether the agency has the statutory authority to conduct a premarket review process that bears no apparent resemblance to anything found in the Food, Drug and Cosmetic Act.

The FDA precert program was the target of criticism from early on regarding whether the organizational certification process was equivalent to a premarket review of each application, but the agency has a compelling argument that its traditional review mechanisms are too clunky for the fast-moving digital space. Nonetheless, Senators Patty Murray, Elizabeth Warren and Tina Smith posed the question of whether the FDA believes the law provides the agency with the authorities to conduct the precert pilot, let alone stand up a full-blown precert program.

The letter also raises the question of whether high-risk devices would be allowed to make use of the precert model, and whether the National Evaluation System for Health Technology will be serviceable as a medical device registry in time to sustain the precert program’s momentum.

On the compliance side, the senators state that there is no evidence the FDA has issued an inspectional form 483 to any companies regarding software products, but they also raise the prospect that the precert program’s mechanism for bypassing premarket reviews for individual products could diminish the volume of user fees collected over the course of the existing user fee agreement.

One of the interesting things to consider is the matter of the senators’ home states. Murray is from Washington, not exactly known as a hotbed of med-tech innovation, but Warren’s and Smith’s home states – Massachusetts and Minnesota, respectively – are indeed medical device hubs for traditional hardware medical devices. That does not necessarily mean that the old guard among device makers is pushing back against what they might see as either favoritism to digital or a high-risk enterprise by the FDA that could damage the reputations of all device makers, but that possibility cannot be ruled out, either.

The Unfinished Business of Myriad

The patent law case of AMP v. Myriad handily brought an end to patent subject matter eligibility for DNA, but the Supreme Court’s June 2013 decision in the case left a few moving parts in play for the life sciences. A case recently emerging from the Court of Appeals for the Federal Circuit suggests that while the outcome in Myriad left complementary DNA in a good place where Section 101 tests are concerned, the use of oligonucleotide primers may now be an appropriate topic for another look if the remarks by one of the judges at the Federal Circuit are any indication.

The Federal Circuit decreed in Roche v. Cepheid that the contested Roche patents, which Cepheid was alleged to have infringed, were not patent eligible, principally because of the test’s reliance on amplified DNA. However, the test also makes use of a number of oligonucleotide primers, which is where the three-judge panel was split.

Judge Kathleen O’Malley made the point that there was nothing in the Supreme Court record for Myriad that spoke directly to the question of subject matter eligibility for these primers, and she said there was some confusion at the Federal Circuit on that point as well. Strictly speaking, O’Malley’s opinion is a concurrence, but she clearly believes the Federal Circuit botched a chance to clarify an issue that is pertinent to a number of diagnostics that make use of primers during the amplification process.

O’Malley said the mere fact that the primers replicate the DNA in question does not necessarily mean the primers are entirely identical to the DNA of interest, but it is not clear yet how Roche intends to respond. The case drew the attention of several patent blogs, but by no means all of them, so this is as yet a niche legal issue. That could change quickly, however, if the question arises again, which seems nearly certain given the widespread use of polymerase chain reaction technologies for in vitro diagnostics.