Industry: FDA Staffing a Key User Fee Issue

Negotiations are underway between the FDA and industry regarding MDUFA V, the fifth medical device user fee agreement, but there are still some issues with the current agreement. One of those, according to industry representatives, is that the agency still has not hired all the staff it had committed to under MDUFA IV, an omission they say must be corrected expeditiously.

According to the transcript for the Oct. 27, 2020, meeting for MDUFA V, Janet Trunzo, senior vice president for regulatory affairs at the Advanced Medical Technology Association (AdvaMed), said user fees promote rather than distract the FDA from fulfilling its mission of protecting public health. Trunzo also said user fees have allowed the FDA’s Center for Devices and Radiological Health to hire hundreds of scientists, engineers and medical officers, and that interactive reviews have enabled a faster, leaner resolution of issues encountered in premarket submissions.

Nonetheless, Trunzo recommended that the agency complete the hiring of all staff that were agreed to and funded by MDUFA IV “as soon as possible.”

That perspective was echoed by Mark Leahey, president and CEO of the Medical Device Manufacturers Association. Leahey expressed some concern about the ever-rising volumes of user fees with each agreement, but added that the agency has yet to make approximately 50 hires agreed upon under MUFA IV.

Leahey also questions the FDA’s method for calculating the cost of each full-time equivalent (FTE) employee. He said the agency’s practice is to divide the total device review budget by the number of FTEs to arrive at the cost per FTE. Device makers are waiting for some information from the agency about this calculation, Leahey said, adding that industry seeks to arrive at a more appropriate approach for making such calculations.

Fees Supplemental, not Primary Revenue Sources

MDMA’s Leahey said the primary responsibility for FDA’s funding sources is congressional appropriations, and that user fees were always seen as supplemental to appropriations. That perspective should be maintained as the negotiations grind on, he said.

The first device user fee program yielded $144 million and jumped to $312 million under MFUFA II. The volume of fees doubled in each of the following iterations and will amount to more than $1 billion under MDUFA IV when all is said and done. Leahey said user fees amounted to more than $200 million in fiscal year 2019 alone.

Peter Weems, senior director of policy and strategy at the Medical Imaging & Technology Alliance, did not specifically call out the dollar figure for the next user fee program, but did state that MITA does not anticipate any need for major new programmatic initiatives or major new commitments. The association’s position is that all programs assembled with the help of user fees should be revisited to determine which should be sustained going forward, and which should be halted if there is a determination that the need is no longer there.

FDA commissioner Stephen Hahn had no reservations about another expansion of total user fees. Hahn stated that the device user fee program and the associated resources “are only a fraction of the size of the programs for prescription and generic drug user fees.” This fact makes the success of the device user fee programs “all the more remarkable,” he stated.

Hahn said he is concerned about the long-term health of the device user fee program, given the pace of innovation in the device industry. The next user fee agreement will give stakeholders a chance “to see what investments we can make in human resources and programs” that enhance communication between sponsors and the agency, he said, a statement he applied to registries as well. Hahn more or less reiterated that view toward the end of his remarks, stating that the negotiations will also provide an opportunity “to consider how we can provide technological, programmatic and other resources to the device team,” including human resources.

EU releases IVD Risk Classification Framework

The medical device regulatory office for the European Commission (EC) finalized a guidance for risk categorization of in vitro diagnostics (IVDs), but concerns about the related implementation date persist. Despite the fact that the original implementation deadline was suspended for a year, many of the affected parties are arguing that industry needs at least another year to implement the new regulations because of the impact of the COVID-19 pandemic on the IVD ecosystem in Europe.

The Nov. 13, 2020, risk classification document by the EC’s Medical Devices Coordination Group (MCDG) employs a four-tier risk scheme, with class D the highest risk category per the manufacturer’s statement of intended use. Any software used with an IVD would necessarily fall into the same risk category as the device with which the software is used.

Despite that the implementation date for the overall IVD regulation has already been suspended for a year, MedTech Europe preemptively argued in July that a number of crucial elements in the regulatory ecosystem are not yet in place. Among the missing building blocks cited by MedTech Europe is a body of guidance documents that are up to the task of explaining the regulations, but the association also noted that there is an insufficient number of notified bodies to handle the impending volume of test recertifications.

Serge Bernasconi, CEO of MedTech Europe, stated that the diagnostics industry is still committed to assisting in the effort to recover from the COVID-19 pandemic, but said the impact of the pandemic on the IVDR implementation “has been considerable, and this must be neither underestimated nor ignored.” In an attached position paper, MedTech Europe called for a delay beyond the existing implementation date of May 26, 2022, but offers no specifics regarding the term of any additional delay.

Ambiguity in Intended Use a Possible Problem

The document is divided into seven rules for risk classification, such rule 2, which covers devices intended for use in blood grouping. Product labeling should clearly spell out the intended use of the diagnostic and the related risk classification, and any ambiguity on this point may lead to a higher risk classification than that proposed by the test maker. There is also some variability within tests for a specific biological agent. The guidelines state, for instance, that a screening test for syphilis would likely fall into class D, but a test to diagnose syphilis in the individual is more likely to be deemed a C risk device.

The guidelines are intended to apply uniformly across technologies, although two tests using the same specimen type may or may not be deemed to fall into the same risk classification. Tests and any associated devices, including software as a medical device, that are used to detect exposure to or the presence of a transmissible agent in the blood, blood components or other organs would be class D devices when those tissue products are intended for transplant, transfusion or administration of cells for therapeutic uses. However, a class D designation might not attach to the same test for such pathogens when conducted for other purposes.

Also among the rules listed in the guidelines are those for devices for self-testing and tests for sexually transmitted diseases. Companion diagnostic tests would fall under class C, as are tests to determine the stage of the disease. Conversely pregnancy tests and tests for fertility are slotted into class B. The guidelines provide classification for instruments, reagents and calibrators as well. Test developers will be liable for annual surveillance assessments for class C and D tests, but not for class A and B tests.

HHS Announces Delayed HIT Compliance Deadlines

The Department of Health and Human Services has responded to concerns about compliance dates for healthcare IT with an interim final rule that relaxes those deadlines by nearly half a year. According to the Oct. 29 HHS press release, vendors of health IT systems have until April 5, 2021, to comply with information blocking provisions of the 21st Century Cures Act, a delay some saw as critical due to the COVID-19 public health emergency.

The Office of the National Coordinator (ONC) had released the final rule March 9, 2020, which in addition to the information blocking provisions included certification requirements for application programming interfaces (APIs). ONC director Don Rucker emphasized that this latest delay does not eliminate the rules requiring greater patient access to their health information, but is intended to allow developers to focus on the pandemic.

In April 2020, the ONC exercised enforcement discretion by adding three months to several of the compliance deadlines included in the March final rule, making the Oct. 29 delay the second such announcement this year. In addition to the delay until April 2021 for the Cures Act’s information blocking provisions, the ONC will allow developers until Dec. 31, 2022, to demonstrate that their software complies with the updated requirements for API functionality.

The Healthcare Information and Management Systems Society Inc., (HIMSS) of Chicago, said the announcement allows the health care sector to focus on the pandemic while sustaining a path forward toward greater patient access to their own information. HIMSS stated that the scope of the information blocking provisions will expand in October 2022, prior to which developers will have to demonstrate only that they are providing access to a limited number of elements initially included in the U.S. Core Data for Interoperability. This will allow developers to become more accustomed to these requirements prior to the compliance date of Oct. 6, 2022, when the full scope of a patient’s electronic health information becomes mandatorily accessible to patients.

The American Health Information Management Association (AHIMA), also headquartered in Chicago, applauded the delay in an Oct. 29 statement. AHIMA CEO Wylecia Wiggs Harris, said the additional delay “is a prudent decision, as the reallocation of resources due to the COVID-19 pandemic has made it challenging for many health information professionals to ensure their institutions are sufficiently in compliance.” Harris thanked ONC “for being cognizant of the realities health information professionals are encountering during the COVID-19 pandemic.”

CMS Resets Two DME Policies

The Centers for Medicare & Medicaid Services released two policy changes, one each for competitive bidding for durable medical equipment (DME), and the other for how items are categorized under the Medicare Part B DME benefit. Of the two, the more immediate impact on patients may be created by the Oct. 27 CMS proposal to classify all continuous glucose monitors (CGMs) as DME, providing broader coverage of CGMs than has been available up to now. At present, Medicare covers these devices only when approved by the FDA for use in making treatment decisions for those with diabetes, such as changes to insulin dosage or to diet.

The policy change would provide coverage for CGMs for more routine considerations, such as potentially hazardous overnight glucose excursions. CMS also made note of the fact that one in every three Medicare beneficiaries suffers from diabetes. The proposed rule would also expand the DME classification of external infusion pumps to permit more in-home use.

The second CMS announcement regarding DME for the week ending Oct. 30 stated that the competitive bidding program would be delayed again for most items. Two items, off-the-shelf (OTS) knee and back braces, will be subject to bidding in 2021, and CMS indicated that the bidding process may save $600 million over the three years of the bidding program for these two items.

The 2021 round of bidding had originally included non-invasive ventilators, a category the agency removed because of the COVID-19 pandemic. OTS back and knee braces were not included in previous bidding programs, but bidding for the other 13 categories was dropped because previous bidding rounds failed to deliver on the anticipated savings.

The American Association for Homecare lent its support to the changes to the bidding program, stating that the program has established a price floor for the 13 devices that will be exempt from bidding year. The statement also recommended that bidding for these products be permanently ended.

CMS Floats Coverage Policy for Breakthrough Devices

The Centers for Medicare & Medicaid Services recently unveiled a new plan to offer four years of Medicare coverage for any medical devices cleared or approved through the FDA’s breakthrough devices program. The news won raves from medical device associations, but the offer comes with a postmarket study requirement that may exceed the demands usually imposed by the FDA for breakthrough devices.

The CMS announcement describes the terms of the Medicare Coverage of Innovative Technology (MCIT) pathway as providing coverage on the same date as the FDA marketing authorization. This coverage would last four years, an offer that assumes, but does not mandate, that the sponsor of the device continues to collect data in the postmarket realm.

Following the four years of MCIT coverage, that device would have to be covered by one of the conventional Medicare coverage mechanisms. In addition to national and local coverage determinations, the CMS press release cites claim-by-claim decisions as one of the post-MCIT alternatives. However, the agency advised that a coverage with evidence development outcome may follow the fourth year of MCIT coverage, adding that participants may be incentivized to gather postmarket data.

CMS said the MCIT program is available only to breakthrough devices that fit within an existing Medicare benefit category, while coverage is limited to on-label use. Device makers are encouraged to communicate with the CMS during the four-year coverage period, but the agency also suggested that sponsors of MCIT devices communicate their interest in an NCD or LCD before the four years are up.

‘Reasonable and Necessary’ Defined

CMS also offered a definition for the term “reasonable and necessary,” which would eventually be codified in the regulation. This definition would address all coverage decisions, rather than being limited to the scope of the MCIT program.

As described in the regulatory notification, the first prong of the three-part test for whether a device or service meets the definition of reasonable and necessary is whether the device is safe and effective. The second prong stipulates that the device must not be strictly experimental or under investigation for the use in question, but the third prong is more complex and asks whether the device or service is appropriate for Medicare patients.

The process for determining appropriateness can be fairly complicated, starting with determining whether the device’s use is consistent with accepted standards of medical practice. The device or service must also be “at least as beneficial as an existing and medically appropriate alternative,” and must not exceed the patient’s need.

However, CMS is offering an alternative mechanism by which appropriateness can be determined. This approach hinges on whether private payers are covering the item or service, although the sponsor would have to demonstrate that the commercially insured individuals are more or less clinically homogenous with Medicare beneficiaries. Sponsors could entirely eliminate the other standards for appropriateness if they can meet this requirement for commercial payer coverage.

The proposal was met with enthusiasm by the trade associations, including the Advanced Medical Technology Association (AdvaMed). Scott Whitaker, AdvaMed’s president/CEO, said in an Aug. 31 press release that the proposed rule would “help ensure the patients who need these innovative technologies have access to them.” Executives from several major device makers also lent their support in the AdvaMed statement, including Mike Mussallem, CEO of Edwards Lifesciences, and John Liddicoat, executive VP for the Americas for Medtronic.

Mark Leahey, president/CEO of the Medical Device Manufacturers Association (MDMA), also supported the proposed rule, something Leahey said MDMA “has long advocated.” He said the association would continue to work with the White House, Congress and other stakeholders to “narrow the gap between regulatory and reimbursement decisions that will bolster patient care.”

FDA Releases Final Guidance for Multiple Function Devices

After a wait of two years, the FDA has concluded the draft guidance for multiple function devices with a final version that makes several substantive changes. Among these is that the list of participating centers now includes the Center for Drug Evaluation and Research (CDER), which was excluded from the draft.

One of the clear indications that the FDA took to heart some of the recommended changes is that the draft covered 18 pages while the final version spans 27 pages. The draft explicitly stated that the scope includes device constituents of combination products, a factor that prompted at least one trade group to recommend that the final version include CDER.

Conversely, the draft and final guidances both state that the FDA will offer no insight as to which functions do and do not meet the definition of a device. Both versions apply the same approach regarding the device types for which the agency currently exercises enforcement discretion regarding compliance activities.

One of the more substantial changes to the policy appears in Section V., specifically the paragraphs for separation of the device and non-device functions in design and implementation. The draft guidance makes several overarching recommendations without providing much in the way of detail. However, the final guidance offers much more insight into the agency’s thinking, such as the suggestion that documentation of a risk analysis of the impact of the non-device function may aid the agency’s understanding of the device function under review.

The final guidance briefly discusses design architecture in the context of maximizing functional separation and segregation as a means of managing risk, content that is not seen in the draft. Also missing from the draft is a recommendation that the sponsor take cybersecurity issues under consideration when considering functional separation.

One of the major changes seen in the final guidance is the addition of a flowchart depicting assessments of the impact of non-device functions on the device function under review. One element of the flowchart states that any beneficial effect the non-device function might have on device performance should be included in the premarket filing, assuming the sponsor intends to include such information in product labeling.

In the absence of a determination that there will be any impact, positive or negative, the device maker should document the rationale for such a determination per the company’s standard operating procedures.

FDA Posts New Template for COVID-19 Testing

The FDA’s Center for Devices and Radiological Health has pressed forward with more policy changes to deal with the COVID-19 pandemic in the final days of July 2020, including publication of a template for non-clinical diagnostic testing in the home and other settings. FDA commissioner Stephen Hahn praised the publication of the template as a game changer, although limited supplies might continue to crimp the volume of testing.

The FDA’s July 29 statement explains that the new template will assist test developers in drafting their emergency use authorization applications for tests that can be performed outside a clinical lab setting, such as the home, the workplace, and in educational settings. This test would be available without a prescription, and Hahn said the objective is to ensure there are tests available that would be no more complicated to use than a pregnancy test.

“These types of tests will be a game changer in our fight against COVID-19, and will be crucial as the nation looks toward reopening,” Hahn said.

The Advanced Medical Technology Association said in a July 28 statement that the daily volume of molecular diagnostic tests for COVID-19 reached one million for the week ending July 24. That number is based on a report from a registry operated by AdvaMed and several diagnostics companies, which also states that 80 million total molecular tests have been shipped in the U.S. as of July 18.

Despite the increase in molecular testing, a number of stakeholders are pressing Congress for dedicated funding and clear coverage guidelines for testing. The letter was signed by several each of medical societies, trade associations and non-profit patient organizations, but the House and Senate are at a standstill over their respective economic relief bills, which include the much-needed taxpayer funding for testing.

PTO Eyes Prioritized Patents to Combat Covid-19

The FDA and other agencies at the U.S. Dept. of Health and Human Services have taken a number of measures to push back against the COVID-19 pandemic, but an agency at the Dept. of Commerce is also getting into the fight. The Patent and Trademark Office recently unveiled a prioritized patent examination pilot that will put COVID-fighting applications to the front of the queue, with a special emphasis on small and micro entities.

The May 8 PTO statement indicates that the agency will waive the fees ordinarily associated with priority patent applications, but also that these applications will be processed within six months, assuming the applicant responds to PTO queries promptly. PTO director Andrei Iancu said small businesses and independent inventors “are often the difference makers when it comes to cutting-edge technology,” but “are also in most need of assistance” as the pandemic wears on.

In the accompanying Federal Register notice, PTO said the scope of the program is limited to products that are subject to an FDA premarket review process, such as emergency use authorizations, premarket approvals and new drug applications. Biologics license applications are also within the scope of the program, but continuing original patent applications are apparently excluded. Filings must include no more than four independent claims and no more than 30 total claims. Multiple dependent claims are also out of consideration, and applicants that file for an extension for time to file a reply will lose their place in this expedited program.

FDA Resets Serology Test Policy for Pandemic

The FDA has maintained a steady pace of policy changes in connection with the COVID-19 pandemic, including a May 4 policy that calls on makers of some serological tests to file for an EUA for their tests. The change followed congressional criticism that many of these tests did not work as advertised, but also followed an extended period during which a large number of tests came to market and thus there was a less pressing need for a relaxed policy.

In an accompanying statement, the FDA said the original testing policy under the emergency use authorization program was borne of a need to provide sufficient regulatory flexibility to bring surveillance testing to the medical front lines. A number of serology tests have arrived with claims of FDA approval or authorization despite lacking such a regulatory acknowledgment, but other tests were shown to perform poorly despite otherwise avoiding the agency’s ire.

Consequently, commercial test developers have 10 days to file for authorization under the EUA program after notifying the agency of the results of test validation, or 10 days after the date of publication of the May 4 policy. High-complexity labs that develop their own tests must still forward validation data to the agency, although they are not required to seek authorization via the EUA program. The FDA recommends they do seek inclusion in the EUA listing, however.

The testing policy was updated again May 9 with the news that the first antigen test for the SARS-CoV-2 virus had gained a place in the EUA policy, and the FDA said more such tests will soon be thus authorized. The anticipation regarding antigen testing is that it will rapidly increase the total volume of tests made to the American public, a critical piece in the effort to bring the pandemic under control. However, the agency advised that antigen testing is even more prone to false negatives than molecular testing for viral RNA, and a negative result for an antigen test may have to be checked by a molecular test – usually a polymerase chain reaction (PCR) test – prior to any clinical decision-making.

Still, the FDA noted that antigen tests are less expensive to deploy than PCR tests and usually provide more rapid turn-around. Antigen tests may boost overall testing capacity by millions per day, but the FDA noted that these are intended as diagnostic tests even as the agency noted that they may also aid in the effort to “identify infection rates closer to real time.”

ONC, CMS Delay Compliance Dates for EHR Interoperability

The COVID-19 pandemic has incurred a number of regulatory casualties in recent weeks, and the final rules for electronic health records (EHRs) promulgated earlier this year are two of the latest among those. Not all aspects of these rules were on the same original compliance deadline, however, and vendors will have to delve into the details of these respective delays to keep them straight.

The Office of the National Coordinator and the Centers for Medicare & Medicaid Services posted a joint statement about the delayed implementation date. ONC director Don Rucker said his agency will offer three months of enforcement discretion to EHR vendors “at the end of … certain compliance dates,” a concession to the pandemic. In contrast, CMS administrator Seema Verma stated that hospitals will generally have an additional six months to implement the related requirements.

The ONC announcement was accompanied by a tabular presentation of revised compliance deadlines, many of which simply add three months onto the original six-month deadline. The roll-out of application programming interface (API) functionality was originally subject to a 24-month compliance date, but now enjoys 27 months of regulatory relief. Many other requirements, such as the information blocking requirement, were initially on a six-month delay from the date of the final rule, but this requirement will not be in force until the end of the year at the earliest. The ONC rule appears in the Federal Register with a date stamp of May 1 and an effective date of June 30.

The CMS stated that the requirements for the patient access API are now in force as of Jan. 1, 2021, the same date as the provider directory API. The CMS requirement for information blocking enjoys a less crisply defined compliance date of “late 2020,” while payer-to-payer data exchange functions must be up and running by Jan. 1, 2022.

FDA Posts AE Reporting Policy

Among the pandemic-related considerations undertaken by the FDA is a policy document spelling out the agency’s expectations regarding adverse event (AE) reporting. The terms of the policy apply to medical products and dietary supplements, and deals with the prospect that COVID-driven absenteeism might hamper a company’s AE reporting program.

The policy, which updates a 2012 guidance addressing influenza outbreaks, allows companies to focus their AE reporting efforts on products related to the COVID-19 pandemic. Affected companies are expected to develop a continuity of operations plan (COOP), which should spell out AE reporting and updates for any events that are stored during the pandemic. Companies should document the start and ending dates of their nations’ emergency declarations as well as the impact of absenteeism on AE reporting.

The FDA says it “does not plan to object” if a company is unable to file AE reports on time due to absenteeism caused by they pandemic, but the affect entities have to file those reports within six months of restoration of normal order of a company’s operations. Companies that can report at least some AEs in a timely fashion must do so, and firms that can file all required reports are expected to make timely reports. If the agency expresses concern about reports in connection with specific products or a particular set of circumstances, the FDA will offer no leniency on the standard reporting requirements, the guidance states.

FDA Reacts to Coronavirus as Stimulus Bill Passes

The FDA is scrambling to meet the demands imposed by the COVID-19 outbreak, including a series of guidances dealing with a variety of issues. However, the predicament has also prompted two pieces of legislation, one an economic stimulus package and the other a bill that would tie the FDA’s hands where regulation of lab-developed tests is concerned.

After considerable wrangling, the U.S. Senate and the House of Representatives sent the Coronavirus Aid, Relief, and Economic Security Act (CARES Act, or H.R. 748) to the Oval Office, which President Trump signed into law March 27. This was the latest – but perhaps not the last – of legislative packages to offset the damage done by the SARS-CoV-2 virus.

The FDA has ramped up a series of guidance documents to deal with the pandemic. One of the earliest policy documents was a Feb. 29 guidance by the FDA’s device center, which the agency updated March 16 to give the states more leeway to ramp up testing. The pandemic was widely seen as potentially crimping ongoing clinical trials, leading the FDA to post a guidance to deal with such concerns. In a March 18 statement, the agency acknowledged that protocol deviations may be unavoidable, and that study protocols may thus have to be amended. One of the related changes the FDA will allow is the use of telemedicine for some patient follow-up appointments.

Another piece of the regulatory puzzle for coronavirus in the U.S. is the FDA’s enforcement policy for ventilators and other respiratory devices. This policy guidance spells out the conditions under which product labels and device functionality of ventilators and other respiratory devices would not be subject to the usual enforcement standards. The emphasis here, the agency said, is to allow manufacturers to add production lines to existing sites and to allow manufacturing at alternate sites. Among the 13 product codes listed within the scope of the document are those for oxygen conservers and anesthesia gas machines.

The agency’s device center has routinely updated a coronavirus FAQ for diagnostic testing, including updates on swabbing procedures and sites that would be acceptable for testing. In a March 23 statement, the FDA made note of a concern that the SARS-CoV-2 virus could be passed along during fecal microbiota transplantation procedures. There is also some concern that cancer patients may be at greater risk of contracting COVID-19 due to compromise of their immune systems.

The FDA also took action on respirator masks in a March 27 statement to the CDC, which authorizes the use of all disposable filtering facepiece respirators that have been approved by the National Institute for Occupational Safety and Health. The scope of this policy includes NIOSH-approved respirators that have passed product expiry, assuming these items are not damaged and have been stored in the appropriate conditions. Two days earlier, the FDA dropped an enforcement policy document for the use of face and respirator masks, which includes some conditions for reprocessing of these items.

Bill Would Ban FDA Regulation of LDTs

Sen. Rand Paul (R-Ky.) has drafted a bill that would disallow FDA regulation of lab-developed tests, at least in part a reaction to the agency’s laggardly response to the SARS-CoV-2 virus. Paul said in a March 18 statement that S. 3512 would remove “unnecessary government barriers that have drastically slowed the response to the COVID-19 outbreak. The Verified Innovative Testing in American Laboratories (VITAL) Act of 2020 would affirm that the Public Health Service Act “governs all aspects” of lab-developed testing procedures, according to the associated fact sheet.

The bill states that “all aspects of a laboratory-developed testing procedures shall be regulated” under Section 353 of the Public Health Service Act, and that “no aspects of laboratory-developed testing procedures shall be regulated under the Federal Food, Drug, and Cosmetic Act.” This would apply during public health emergencies as well as during periods of normal activity.

Paul’s bill comes shortly after two members of the House of Representatives resurrected the Verifying Accurate, Leading-edge IVCT Development (VALID) Act, which has been modified from previous iterations to address the COVID-19 outbreak. Reps. Diana DeGette (D-Colo.) and Larry Bucshon (R-Ind.) said their legislation would create a new product category for diagnostic and lab tests, but they also point to the need to allow labs to respond quickly to public health crises. The bill would allow developers to electronically file their tests for FDA review.

There is a companion bill for the VALID Act in the Senate, but there is also some question as to whether either of these bills will pick up any traction this year, given the impact of the coronavirus on congressional schedules. It might be noted that discussions regarding the fiscal 2021 budget have been displaced by the COVID-19 outbreak at least for the time being, and that the upcoming election is likely to bring a halt to routine legislative activity by the end of August.

Coronavirus Prompting Reaction in Washington

The newest mutation to the coronavirus has had a massive impact in China and has prompted a reaction from the World Health Organization (WHO). The impact on makers of devices and diagnostics has been minimal so far, but the signs are that this could change quickly if the virus continues to proliferate.

The 2019-nCoV virus has prompted two press briefings by a U.S. federal government task force led by HHS Secretary Alex Azar, developments that followed a Jan. 31 declaration of emergency by WHO. Much of the concern about the virus is that it can be transmitted even from those who are asymptomatic, but the test for the virus developed by the U.S. Centers for Disease Control and Prevention has proven less than fully reliable.

Robert Redfield, director of the CDC, said in a Jan. 31 press briefing that the CDC test will return both positive and negative results on a patient who has been confirmed to carry the pathogen. The U.S. government response has been questioned, given that influenza is still proving more lethal, but Anthony Fauci of the National Institute of Allergy and Infectious Diseases said influenzas predictably fade as winter gives way to spring, whereas the trajectory of the new coronavirus is unknown.

The FDA recently issued an emergency use authorization for the CDC test, a reverse-transcriptase polymerase chain reaction test to be used with swabs from the upper and lower respiratory tracts. The CDC posted a press release two days later in which the agency said the test will initially be shipped to roughly 200 domestic sites and another 200 sites located in other nations. The test provides results within four hours, CDC said.

The Department of Health and Human Services posted a Feb. 6 announcement stating that HHS is taking submissions for diagnostics that would receive federal funding under the Biomedical Advanced Research and Development Authority (BARDA) program. This program requires that the test in question would have to be available on a platform already cleared by the FDA, and that the test would be ready for live use within 12 weeks of receipt of the award.

Congress Prods FDA for Assurances

Capitol Hill has demonstrated some concern about the impact of the coronavirus outbreak on the availability of medical products from China. Two members of the Senate, Florida Republican Marco Rubio and Connecticut Democrat Chris Murphy said in a Feb. 6 statement that they have a series of questions they would like answered by Feb. 18. Among the questions is whether the FDA has the resources to determine whether the impact of the coronavirus in China will affect the availability of drugs and devices for U.S. patients.

Murphy and Rubio noted that China is the source of the majority of active pharmaceutical ingredients used to produce drugs in the U.S., and that 10% of devices used in the U.S. are also imported from China. FDA commissioner Stephen Hahn said in the Feb. 7 press briefing that there was no evidence of any slowdown in the supply chain of the various products in question at that point in time, but he noted that the situation “is fluid” and that this could change in short order.

Perhaps as disturbing as any other recent event associated with the coronavirus is the discovery that more than four in 10 coronavirus patients in a hospital in China had contracted the virus while at the hospital. The majority of the patients presumed to have contracted the virus at the hospital site were employees of the hospital, although this single-site study might not reflect the broader experience in China. Nonetheless, the authors say that as many as 10 health care workers had presumably been infected by a single patient.

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.