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’ September Surprises

The October surprise may be the stuff of electoral legerdemain, but drug and device makers are seeing a few interesting legal twists inside and outside the courtroom in the month of September. In one instance, PMA preemption is back in the news, while another story involves what seems a very generous sale of intellectual property assets forced by multiple patent challenges.

Lassoed Again by the Riata

Despite best intentions, sometimes an old drug or device comes back to haunt its maker. This would appear to be the case with the Riata and Riata ST series of electrophysiology leads made by St. Jude Medical, now a subsidiary of Abbott. While this seems a fairly typical preemption case, Connelly v. St. Jude Medical seems to revive the issue of a litigant’s access to confidential commercial information.

According to documents from the U.S. District Court for the Northern District of California, Richard Connelly received a total of three Riata leads between 2003 and 2015. Connelly’s attorneys argued liability on the basis of manufacturing defects, failure to warn, negligence and negligence per se, and Abbott responded that the first three claims are explicitly preempted while the last is truncated by implied preemption.

Judge Edward Davila rejected the failure to warn claim, albeit with a possible amendment of the claim, the same determination he came to regarding the negligence per se claim. Avila gave the plaintiff until Sept. 8 to amend those claims, which apparently his counsel has done.

However, Avila affirmed the manufacturing defect claim partly because the plaintiff’s attorneys had no access to the entirety of the documentation for the regulatory filing. The basis of the manufacturing defect argument commenced with three pieces of evidence; an FDA inspectional form, the recalls of the Riata series of devices, and an internal root cause analysis undertaken to examine the lead insulation problems.

Avila wrote that California state law does indeed run parallel to federal law on the manufacturing defect issue because the plaintiff had demonstrated “a plausible connection between the alleged manufacturing defect and his injuries.” He based this conclusion in part on a 2014 case in the U.S. District Court for the Northern District of New York, Rosen v. St. Jude, but not much else.

Avila conceded that the Court of Appeals for the Ninth Circuit “has not directly addressed this issue,” but states that a plaintiff’s inability to access confidential commercial information at the time complaint was filed – coupled with factual evidence presumed to be sufficient to demonstrate a causal connection – are all that is needed to sidestep federal preemption and satisfy the requirements of Twombly.

The negligence claim survived on essentially the same set of facts, and the court determined that Abbott is not liable in this instance because its acquisition of St. Jude was not completed until after Connelly was injured. Avila indicated that the plaintiff can amend the complaint on this point as well, however. It seems fairly plausible that this case will end up in Ninth Appeals, regardless of the outcome in this venue.

Allergan’s IP End Run

Most methods for dealing with patent challenges run to the tried and true, but Allergan’s move to insulate its patents for Restasis may have left some members of the patent bar a bit dewy-eyed for not having thought of it themselves.

Allergan has declared it will transfer all patent rights for the treatment for dry eye to the St. Regis Mohawk Tribe, which will confer sovereign immunity on the related patents. This would seem to fend off ongoing challenges via the inter partes review process at the Patent and Trademark Office, but there are suggestions that Allergan has progressively less to lose. While sales of the product exceeded $350 million in the third quarter of 2016, the FDA has yet to decide whether generic versions will have to go through clinical trials in a debate between the agency and the manufacturer that is now in its fourth year.

The company is also fending off a patent challenge in the patent rocket docket in Marshall, Texas, over the production of generics, which some believe will hit the market as early as 2019. The problem for Allergan in this lawsuit, at least in terms of optics, is that the company has already settled with Famy Care Ltd., which will be able to market its generic version no later than 2024 (when the patent expires), and possibly substantially earlier.

Under the terms of the licensing agreement, the St. Regis Mohawk Tribe seems to be doing quite well, indeed, explaining in a Sept. 8 statement that it will receive more than $13 million from Allergan to take ownership of the patents in addition to an expected annual sum of $15 million in royalties.

Cardiaq Sustains Narrow Win Over Neovasc

The patent scrum between Cardiaq Valve Technologies and Neovasc Inc., made it all the way to the Court of Appeals for the Federal Circuit, which has affirmed a district court decision awarding the plaintiff more than $110 million. In Cardiaq Valve Technologies v. Neovasc, Inc., the plaintiff alleged that Neovasc had breached a contract the two companies had signed as part of a development program by Cardiaq toward a transcatheter mitral valve technology, which Neovasc purportedly violated by using some of the intellectual property in an effort to develop its own mitral valve device.

In addition to the initial jury damages of $70 million, Neovasc will have to pay roughly $20 million each for interest and enhanced damages, although neither the district court nor the Federal Circuit agreed to enjoin Neovasc’s development program. While Cardiaq won’t enjoy the kind of exclusivity typically afforded by a patent, it was acquired by Edwards Lifesciences, which has a degree of credibility with cardiologists that Neovasc cannot possibly match in the near term. Thus, while the patent fight seems uncomfortably close to a draw for plaintiff, the physician adoption curve is nearly certain to favor Cardiaq by a wide margin.

Of Pens, Delays, and Balloons

Some stories in the life sciences are years in the making while others take a more swift course to resolution. Below are three stories of varying degrees of persistence, but it may be that we have not heard the last of any of them just yet.

EpiPen Settlement a Sore Spot for Some

The EpiPen settlement between Mylan and the Department of Justice is finally in the books, but there were several interesting developments involved in this action, which has spanned at least the better part of a decade. The company has agreed to pay $465 million to settle these allegations, but there are indications that this matter is not finished.

To recap, the EpiPen controversy was already the subject of federal government interest in 2009, when the Office of Inspector General at HHS cited the Epipen as a product of interest in a report on the accuracy of drug prices for Medicaid rebates. The Aug. 17 DoJ statement announcing the settlement said Mylan had “violated the False Claims Act by knowingly misclassifying EpiPen as a generic drug to avoid paying rebates,” but the DoJ nonetheless stated that the claims “settled by this agreement are allegations only, and there has been no determination of liability.”

The department’s announcement lists only one relator in this qui tam action, Sanofi-Aventis, but Ven-a-Care of Key West, Fla., was also on board. Ven-a-Care is purportedly a pharmacy, but some see the company as more of a bounty hunter, given the frequency with which its owners avail themselves of large sums for similar cases. Thus, the Mylan case was driven by two relators rather than the more typical single relator, suggesting the data provided by Ven-a-Care and Sanofi were substantially different.

Another interesting facet of this case is that non-governmental 340B drug programs will enjoy rebates from the action, which is not ordinarily the case. In any event, this settlement might not be the last word on the controversy as Sens. Chuck Grassley (R-Iowa) and Richard Blumenthal (D-Conn) have criticized the amount of the damages as grossly inadequate.

The drug pricing controversy is providing plenty of whiplash for Valeant as well. Recently, Valeant investor Lord Abbett & Co. filed suit in New Jersey with the argument that Valeant’s actions violate that state’s Racketeer Influenced and Corrupt Organizations law. Should a judge accept that argument, Valeant could face treble damages.

340B Final Rule Delayed Again

In spite of all the consternation about drug prices, the Department of Health and Human Services has announced that it will once again delay a rule that would have dinged drugmakers for overcharging several types of institutions, including safety net hospitals.

The related provisions of the Affordable Care Act had expanded the types of institutions eligible for participation in the 340B program to include children’s hospitals and free-standing cancer centers, but the latest 340B final rule would have hit drugmakers with a $5,000 fine for each instance in which the charge for a drug exceeded the ceiling price. This is the third time the implementation date of this final rule has been pushed back, which is now suspended until at least July 2018. The move was blasted by a number of affected entities, but there are rumblings that the 340B reporting portal administered by the Health Resources and Services Administration is not fully operational.

Rates for Drug-Coated Balloons may Crater

A Medicare advisory board will recommend that the Centers for Medicare & Medicaid Services allow reimbursement for drug-coated balloons (DCBs) to lapse to the rates paid for standard angioplasty of the lower limbs. The decision flew in the face of clinician input, but whether CMS will go along with the advisory panel’s recommendation is not yet clear.

The Medicare advisory board for the outpatient prospective payment system said the rates paid for DCBs – such as Medtronic’s Admiral InPact and the Lutonix by C.R. Bard – should be allowed to fall to the rates paid for standard angioplasty balloons used in the femoral and popliteal arteries. DCBs enjoyed a higher reimbursement rate under the Medicare new technology pass-through program, but these devices have used up their eligibility for the program. This predicament leaves Bard and Medtronic facing a rate as low as $4,999 in calendar year 2018, a rate that clinicians said would impede access and possibly trigger a spike in the amputations DCBs are credited with preventing.

Physicians have argued that the use of a DCB requires both pre- and post-dilatation of the target vessel with a plain balloon to achieve the desired effect on vessel patency, a necessity that boosts both procedure time and costs. An industry representative suggested a rate closer to $8,000 for DCBs, but the panel clearly was not amenable. The panel endorsed a proposal that CMS track costs and utilization of these devices in CY 2018 in order to evaluate whether a new ambulatory payment classification code is needed to account for the costs associated with DCBs, but that proposal leaves patients and physicians with a 12-month question mark.

In the meantime, hospitals and other institutions will have to decide whether to take the financial hit for these devices in an effort to avoid readmissions, which are squarely in CMS’s crosshairs via several well-known health care delivery reform programs.

Going Solo, and Who Needs Government Anyway?

Some days it seems the idea of interdependence is really gaining ground, but then there are days that seem to trash the idea completely. Below are a couple of stories of the latter variety, stories that might seem more pointed to the diversity ethic that is also very much in vogue in these early years of the 21st Century. First, however, we ask whether the FDA’s device center is losing its appetite for heavy-handed regulation.

FDA Going Soft on Software?

The Center for Devices and Radiological Health at the FDA was pretty quiet for the first half of the year, but is a little more active recently. For instance, CDRH published a digital health action plan in response to pressure from Congress, but the plan is also a tacit admission from the agency that its quality systems regulations (QSRs) don’t always work well where software is concerned.

The reader may remember the FDA’s interest in medical device data systems dating back to 2011. Hospital administrators were wary of the cost and hassle of standing up a QSR-compliant regime in the first place, but four years would pass before the agency renounced the idea, undoubtedly with the help of some arm-twisting from Capitol Hill.

The FDA’s digital health innovation action plan includes a precertification pilot that calls for a review of a publisher’s approach to software quality control rather than a full-blown premarket review of each product. The program is limited to items that qualify as software as a medical device (SaMD), however, and excludes items such as software integrated into devices.

The precertification pilot does include site visits, but the agency is willing to conduct virtual site visits in lieu of the real thing. Ergo, one can argue that this is QSR-lite at worst. Still, one has to wonder how much time will pass before an SaMD will start pushing the FDA’s safety and efficacy buttons despite FDA commissioner Scott Gottlieb’s assertion that the program is strictly for “certain lower-risk devices.” That lower-risk assurance seems odd, given that the sponsor will be on the hook for collecting post-market data for that product.

The day one of these calls for a de novo application might herald a time when the agency will scrutinize these SaMDs individually, but how long after that will a sponsor discover they have tripped the class III/PMA trigger? Only time will tell.

Disharmony from Asia

Some see global regulatory harmonization as a pipe dream, and India’s Central Drug Standards Control Organization has released a draft guidance dealing with standards for safety and performance of medical devices that would seem to support that view. This document, which supplements a novel regulatory framework specific to med tech in India, suggests that CDSCO will handle stand-alone software in the same manner as traditional medical devices despite the FDA’s hands-off approach.

CDSCO gave interested parties only three weeks to comment, hardly sufficient time to absorb the implications of such a document, particularly since the document is undated, other than to note the month of publication (July). The agency said it does not want to dictate how a device maker might demonstrate compliance, but the scope of the 27-page document encompasses a wide range of product categories, including combination products, a breadth of scope which might come across to some as lack of specificity disguised as flexibility.

In any case, the document also takes aim at devices “that incorporate software and stand-alone medical device software,” which is where it rubs up against the new approach at FDA in a disharmonious manner.

As noted above, the American regulator is steering an entirely novel tack for its regulation of SaMD, which had said last year would revolved around a guidance drafted by the International Medical Device Regulators Forum. India is not a participant in the IMDRF effort, although it is a member of the Asian Harmonization Working Party (AHWP), which is an IMDRF affiliate and which has inked its own SaMD proposal, said to be built around the IMDRF effort.

One way of looking at this is that the FDA is the outlier and that the disharmony is coming from Silver Spring, Md., and not from New Delhi, although it may be instructive to note that the latter has a very limited body of experience with med tech-specific regulations. Either way, publishers of SaMD will continue to face very different regulatory regimes if they want to do business in both the world’s richest market and its second most populous market.

No DOJ? No Problem

As is commonly known, the Department of Justice does not dive head first into every qui tam action that pops up, but government attorneys seem to be involved in nearly every whistleblower suit that costs the target company money. Celgene of Summit, N.J. offers the exception, getting stung with a $280 million hit in a False Claims Act case that asked the federal government to do nothing more than accept a nice, fat check from the company.

The company denied any culpability, and Celgene may have a case given that the Centers for Medicare & Medicaid Services is somewhat more lenient about off-label use of oncology drugs. However, court documents indicated that Celgene helped patients financially by contributing money to two patient-directed organizations, which were said to have “acted as conduits for Celgene” and thus had “eliminated any price sensitivity” for both patients and prescribing physicians.

The court also said “the United States did not intervene” without comment, although the court pointed to two other qui tam actions against the company, both of which were dismissed.

The biggest problem for Celgene might have been that the company purportedly persuaded physicians to influence guidelines published by the National Comprehensive Cancer Network, and was alleged to have “caus[ed] doctors to change ICD-9 diagnosis codes.” The lay person sitting in a jury box might find it difficult to hear of manipulation of codes used in Medicare billing without thinking the source of that manipulation was up to no good, particularly given how much very visible emphasis there is these days on Medicare fraud.

Status of Medical Device Reprocessor/Refurbisher Liability

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

Status of Reprocessor Liability

The recent pressures to drive down the cost of medical care have given way to a practice of using medical devices (even so-called “single-use devices”) a greater number of times, on a greater number of patients, before disposing of them. To accomplish this, hospitals are increasingly using reprocessors to sterilize and re-validate their devices between uses. Although device reprocessing is nothing new, the increase in demand has largely altered the general practice from one in which hospitals sent its devices to a reprocessor and got those exact units back after reprocessing, to one in which the reprocessor provides the hospital with the same model of devices that the hospital submitted but not necessarily the same specific units submitted. This allows for a faster turn-around time.  In this process, the reprocessor may often re-serialize the devices and alter the labels, warnings, or instructions for use, hopefully to account for any additional precautions medical personnel must need to take in light of the manner of reprocessing.

FDA Regulation

Medical device refurbishing is an interesting area right now as it has recently become a focus for FDA and a potential subject of new regulation. Last Spring, the FDA sought industry feedback on proposed definitions including repair, refurbish, remanufacture, recondition, and remarket. At the same time, the Agency also solicited answers to questions about the risks and failure modes introduced as a result of performing these activities on medical devices, and whether the risks were different depending on who performs the activities (hospitals, OEMs, third parties). Thus far, though over 200 comments were submitted in response to these questions, there has not been any further movement from the FDA in this area. Many have speculated that when the Agency does take action, it will likely be to bring refurbishers under the same oversight scheme as reprocessors of single-use devices.

Kapps v. Biosense Webster, Inc.

Although the presence of reprocessors in the chain of distribution presumably has products liability implications for the original-equipment manufacturers (OEMs), few cases have addressed the issue of strict products liability for manufacturers when a device malfunctions after it has been reprocessed or refurbished. The most recent case that really explored this issue was Kapps v. Biosence Webster, 813 F.Supp.2d 1128 (D.Minn. 2011), a case that came out of the Federal District Court of Minnesota in 2011. Though several years old now, the Court’s analysis provides some valuable insights into distinctions that may be important in deciphering products liability apportionment between OEMs and reprocessors. It’s easy to extrapolate that similar reasoning would apply to refurbishers.

In Kapps, the plaintiff was an atrial fibrillation patient that underwent a procedure in which doctors used a “lasso catheter” that had been reprocessed.  During the surgery, the lasso portion of the catheter separated and remained entangled in the plaintiff’s mitral valve. It was eventually able to be removed by the doctors, but the damage that was sustained to the plaintiff’s mitral valve in the process necessitated additional open-heart surgery and replacement of his damaged valve with a prosthesis.

The plaintiff brought the usual products liability claims—manufacturing defect, warning defect, design defect, breach of warranty, and negligence—against both the OEM and the reprocessor.

The Court held:

  1. Plaintiff cannot rely on res ipsa loquitor to establish the OEM’s liability for manufacturing defects.

Res ipsa loquitur is a doctrine used in negligence and products liability actions when the plaintiff has incurred some harm, but obvious difficulties may make too difficult for the plaintiff to prove the exact origin of the cause of harm. In order to utilize res ipsa, plaintiffs (generally) must first establish both that (1) the accident—here, the defect in the product—is the kind that would usually be caused by negligence; and (2) that the defendant had exclusive control over the instrumentality that caused the accident—here, the manufacture and composition of the device.  In disallowing the plaintiff to rely on res ipsa against the OEM, the Court relied on the fact that at the time of injury, the reprocessed device could not be said to have been in the same condition it was when it left the OEM’s control. In effect, the second prong was not satisfied as the OEM did not have exclusive control over the condition of the catheter once the reprocessor was used.

  1. Claims against the reprocessor are viable under theory of res ipsa loquitor.

In contrast, because the reprocessor did have exclusive control over the condition of the catheter as it was at the time of the injury, the Court held that res ipsa loquitur could be applied to the negligence claim against the reprocessor.

  1. An OEM that markets its device as single use will be immunized against the claim that it nonetheless should have foreseen and warned that a reprocessor might ignore the single-use instructions.

In Kapps, the OEM of the catheter has specifically labeled the device, and included in its instructions for use, that it was intended for single use only. Nonetheless, the plaintiff claimed that the OEM should have foreseen that the catheter would likely still be reprocessed despite such instructions, and warned accordingly of the dangers of reprocessing. The Court rejected this claim.

  1. Reprocessor carried a manufacturer’s duties to warn and to provide a defect-free product, because it acted (a) replaced the OEM’s instructions for use and product serial numbers with its own; (b) warranted the functionality of the reprocessed device; and (3) marketed the product as its own equivalent to the OEM’s.

The reprocessor responded to the warning-defect allegations of the plaintiff’s by asserting that the duty to warn should lie only with the OEM. The Court did not find this argument compelling, and instead held that the reprocessor in these circumstances indeed had the same duty to warn as an OEM has.

Kapps can provide helpful guidance for OEMs and reprocessors alike.  For OEMs, it may be reassuring that they may not be strictly liable for manufacturing defects after the their device has been reprocessed, but they must be careful to include warnings and instructions for reprocessing and its dangers if in fact their device is not designated for single use only. Reprocessors should be mindful of enlarging their own products liability when they mix, re-serialize, and alter the warnings and labels of an OEM’s devices.

State Statutes

In the years since Kapps, courts haven’t been asked to reconsider the issue of reprocessor/refurbishers liability hasn’t come before the courts again, so it’s the best indication we’ve got as to how courts are likely to treat reprocessor liability going forward. That said, several states aren’t waiting for the courts to decide, and some have enacted statutes specifically deeming reprocessors and refurbishers to have the same liability with respect to a defective device as original manufacturers. See, e.g., Utah’s statute, U.C.A. 1953 § 78B-4-505. Liability of reprocessor of single-use medical devices.

Conclusion

The safest course for reprocessors and refurbishers of medical devices is probably to assume that they may stand in the shoes of the OEM if something goes wrong with the device they process. In doing so, they should implement a quality management system and undertake the same robust risk management practices of which successful OEMs make use.

Boomerang: EMA Goes from Hunter to Hunted

Boomerang: EMA Goes from Hunter to Hunted

Regulatory agencies spend more time investigating others than being investigated by others, but the European Medicines Agency is now on the hot seat over what is purported to be a lack of transparency regarding premarket interactions between it and drug makers. This is quite a reversal of the typical dynamic, such as when the EMA orders drug makers to withdraw their products from the EU market, but companies in the life sciences might not think the agency’s new transparency problem is a good problem for industry.

EU Ombudsman Investigating Presubmission Meetings

Allegations that regulators are all to cozy with industry are typically leveled at the American FDA, but that problem seems to have migrated to the other side of the Atlantic Ocean. Former journalist Emily O’Reilly, who took the job of European Ombudsman in 2013, has advised the European Medicines Agency she intends to open a “strategic inquiry” into pre-submission activities between the European Medicines Agency and regulated entities.

O’Reilly is no stranger to controversy, having penned three books that struck a number of nerves, but she also took the government of Ireland to task for what she saw as a problem with transparency. The theme of transparency appears in her July 17 letter to EMA executive director Guido Rasi, which states that pre-submission interactions with EMA staff and industry “may pose some risks,” such as that reviewers at EMA may be influenced by applicants in these interactions. O’Reilly acknowledges that these pre-submission meetings are not necessarily problematic, but said there is risk that these meetings create “in the eyes of the public, at least some perception of bias,” a hazard she asserts “must be managed.”

This risk could be managed by more transparency, O’Reilly continues, stating also that “a preliminary assessment suggests that more could be done in this area” without offering any details related to that preliminary assessment.

O’Reilly inquired as to whether EMA publishes “detailed minutes of pre-submission meetings,” which may strike some in industry as incurring the hazard of loosing the lid on proprietary information. She asked EMA to provide details of such meetings dating back to 2012, and asked for a list of the 10 companies that “met most frequently” with EMA staff in pre-submission meetings.

The inquiry is certain to raise a few hackles, but it’s anyone’s guess as to how far this will go and whether EMA will find this sufficiently distractive to impede the agency’s handling of priority review applications, which are also referenced in O’Reilly’s letter. At the very least, this is a matter that bears watching.

EMA Hits Gadoliniums After FDA Stands Pat

The EMA is no stranger to imposing its will on others, as demonstrated by the fact that it has followed through on a threat to suspend the marketing authorization for three gadolinium-based MRI imaging agents, a move that was not paralleled in a similar FDA review. Among the products up for suspension is one route of administration for Magnevist, a linear gabapentin-based contrast agent (GBCA) manufactured by Bayer Schering Pharma, but the macrocyclic GBCAs escaped relatively unscathed in this review.

The FDA began its investigation into the effects of deposits of GBCAs in human tissues in 2015, but announced in May that it had no data on hand to suggest that retention of these agents in the brain is harmful for most patients. The agency affirmed the notion that linear GBCAs are more the more likely of the two types to be retained in the human body, and said the only known problem is nephrogenic systemic fibrosis, said to occur only in “a small subgroup of patients” who had been diagnosed with kidney failure. The FDA said it would continue to track these patients.

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) said earlier in July that it had confirmed “that there is convincing evidence of gadolinium deposition in brain tissues” with the use of gadolinium contrast agents, but while PRAC did not identify specific conditions in connection with deposits in the brain, the committee recommended that EMA suspend the use of Magnevist (gadopentic acid) and two other linear GBCAs, Omniscan (gadodiamide) and Optimark (gadoversetamide).

EMA’s July 21 announcement confirmed the suspension of marketing authorizations for the three linear agents cited by the PRAC, while stating that another linear GBCA, Multihance (gadobenic acid) should be restricted to use in scans of the liver. Another linear GBCA, Primovist (gadoxeticacid), was untouched by the EMA action, although it should be noted that the agency will allow Magnevist to stay on the market for intra-articular use despite the suspension of its use via intravenous administration.

Venue, Preemption Issues Dot Legal Landscape

The Supreme Court has been busy of late on several fronts of interest to those in the life sciences, and may be busier yet if it accepts a case dealing with preemption. The Court decided a case recently dealing with venue, but there is some disagreement as to how much that decision clarified the questions at hand.

Is Lohr back in play?

Those who find the PMA preemption discussion fascinating will enjoy the potential for a reexamination of preemption for class II devices if the U.S. Supreme Court grants cert for a case addressing surgical meshes. One of the more interesting aspects of this case is that any push for 510(k) preemption might be due to more stringent requirements for these applications imposed by the FDA over the past few years.

J&J subsidiary Ethicon requested cert for Ethicon v. Huskey, which takes up a synthetic surgical mesh applied for stress urinary incontinence. The jury trial returned an award of more than $3 million for the plaintiff, and Ethicon appealed the case on the grounds that the judge in the first trial disallowed evidence as to the company’s adherence to FDA premarket requirements, along with several other bits of regulatory information related to the device.

The appeals court sided with the district court, citing with the Federal Rule of Evidence 403 as justification for omitting the evidence in question, but the appeals court decision also argued that 510(k) filings only “tangentially” deal with safety and efficacy. The court cited Medtronic v. Lohr without comment in this section, which seems likely to provoke a discussion as to whether the FDA’s increasing demands from FDA for 510(k) filings begins to approach the threshold for specificity that is the foundation for PMA preemption. Or at least that’s the argument device makers are inclined to make.

Either way, Lohr dealt with the statute as it existed in 1982, when the FDA cleared the Model 4011 pacemaker, and thus changes imposed by Congress since then, including the Safe Medical Devices Act of 1990, were not considered. This legislation was driven almost entirely by concerns about the tracking of adverse events for class II devices, but the Supreme Court decision in Lohr claimed that a typical 510(k) review takes only 20 hours as opposed to the average of 1,200 hours needed to review a PMA filing.

Whether those times still hold is difficult to know, but the most recent FDA performance report for the soon-to-expire device user fee agreement suggests that overall PMA review times are down to 163 FDA days while the target for 510(k) review times is still 90 FDA days. The question one might ask oneself is: If it takes the FDA 90 days to get through 20 hours of review time for a 510(k), how can it take only 163 days to put 1,200 hours into a PMA?

Venue, vidi, vici

Those who see the question of forum shopping in a negative light might be encouraged by a recent decision in the Supreme Court that seems to put the clamps on this practice. The fact that the decision in Heartland v. Kraft was unanimous would seem to bring the venue question to a thunderous close, but there is some skepticism as to whether the question is fully answered.

Justice Clarence Thomas wrote the 8-0 decision in Heartland  – Justice Neil Gorsuch did not take part – and said that §1400 of Title 21 of the U.S. Code was unaffected by congressional modification of Title 21’s §1391. Thomas also pointed to Fourco Glass v. Transmirra Products, the 1957 case in which the Supreme Court declared that the word “resides” means the location of incorporation for a U.S. domestic company.

Former PTO director Todd Dickinson noted that the outcome leaves a few questions unanswered about cases that are already in process, but he also said that stand-alone legislation by Sen. Jeff Flake (R-Ariz.) directed toward venue might be futile. On the other hand, former Senate Judiciary Committee chairman Orrin Hatch said he will draft a bill to take up the vexatious venue problem, so there is clearly some interest on Capitol Hill.

There are those who believe that Heartland might influence whether patent litigants will resort to multidistrict litigation to go after infringers. The America Invents Act disallowed the use of joinder based merely on the charge that each of the named defendants infringed the same patent, and Heartland would seem to suggest that a patent holder will spend a lot more time on the road in pursuit of damages, although a lot of potential targets are located in Delaware thanks to that state’s status as the home of the limited liability corporation.

Multidistrict litigation might seem a handy way to pursue infringers in numerous jurisdictions, but MDLs are infrequently used for patent cases. Would the U.S. Judicial Panel on Multidistrict Litigation (JPML) be persuaded by an application to consolidate patent lawsuits when only half a dozen or so defendants are named? By some accounts, patent MDLs currently account for less than 5 percent of all MDLs, although this might reflect nothing more than underutilization.

Still, it seems plausible that a plaintiff will have to identify a very similar set of allegations for a given number of defendants in order to prod the JPML into action. A lack of sheer numbers presents one problem, but the combination of small numbers and dissimilar allegations could prove fatal to an effort to consolidate patent lawsuits via the JPML.