EMA Proposes Delay of MDR Implementation

As the world grapples with the newest version of the coronavirus, regulatory agencies across the globe are reacting with a number of moves, mostly to relax existing regulatory requirements. In contrast, the European Medicines Agency is considering a delay in the implementation date of the as-yet unimplemented Medical Device Regulations, a change that would ease device makers’ concerns on several fronts.

MedTech Europe had posted a plea for a delay from the implementation date, originally set for May 26, 2020, citing the need to address the COVID-19 pandemic. However, device makers were already wary of the practicalities of that original implementation date, largely because of the difficulty in enlisting a sufficient number of notified bodies. The association’s plea was seconded by a range of members of the European Parliament, who made the case that the priority should be device availability until the pandemic becomes manageable.

The proposal to delay implementation for a year was announced March 25, with the acknowledgement that the notion would have to clear the European Parliament. MedTech Europe lent the development its full-throated support, stating March 25 that this change would allow industry to maintain the pressure on the pandemic. Nonetheless, MedTech Europe made the argument that a similar delay is called for in connection with the In Vitro Diagnostic Regulation as well, given the demands of the pandemic on the testing capacity in the EU member states.

Congress Pressing FDA on Serological Testing

The FDA has granted emergency use authorization to a number of diagnostics for the SARS-CoV-2 virus, but until recently, those have all been molecular tests conducted with polymerase chain reaction methods. That approach has drawn the interest of at least one member of Congress, who is urging the FDA to take a more active role in ensuring that serological testing becomes more widely available.

Rep. Diana DeGette (D-Colo.), who is a member of several subcommittees of the House Energy and Commerce Committee, said in an April 10 statement that she had previously made known her views on serological testing to several senior Trump administration officials. She said serological testing for antibodies will prove crucial in returning the country to more routine economic activity, and urged FDA commissioner Stephen Hahn to press the case for serological testing with President Trump. Specifically, DeGette recommended that Hahn suggest the use of the Defense Production Act to boost production of the equipment and supplies needed for serological testing, which would allow those who have already been exposed and have recovered to return to work without incurring any undue hazard.

DeGette may or may not be concerned about the FDA’s stance on the question of false positives associated with serological testing, but the agency said in an April 7 statement that it has been in contact with more than 70 test developers about serological tests. The statement, attributed to Hahn, acknowledges the role that serological tests will play in the months ahead, but also points to concerns about false claims regarding FDA approval or emergency authorization.

Whether the FDA has sufficient data to back the use of serological testing as a population-level surveillance strategy is not entirely clear, but it has an ally in that effort in the form of the National Institutes of Health. NIH said in an April 10 statement that it will commence with a study of the presence of antibodies for SARS-CoV-2 in those who have had no prior confirmed diagnosis, but there is a question of how quickly these data will become available.

According to the NIH, the study will enroll as many as 10,000 subjects who will be consented via telephone, although enrollment is limited to those aged 18 years and older. The study will tests for two immunoglobulins via enzyme-linked immunosorbent assay, and enrollees can handle the blood draw via a home collection kit. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the study should shed light on the “true magnitude of the COVID-19 pandemic” by characterizing the rate of non-diagnosed illness.

The registration of this study at clinicaltrials.gov indicates that enrollment may be completed with as few as 1,000 patients despite the ten-fold higher number noted in the NIH press release. Whether the final enrollment volume will be closer to the lower or upper stated enrollment targets will not be clear for some time, as the estimated primary completion date is March 31, 2022, the same date as the projected full study completion date.

FY 2021 Budget Proposal Hits NIH, Mostly Flat for FDA

The Trump administration’s budget proposal for fiscal 2021 in large part reflected the administration’s past proposals for various agencies at the Department of Health and Human Services. While the proposal largely flat-funds the FDA, the cuts to the NIH budget would be significant, but are likely to be overridden by Congress once again.

The OMB budget proposal for NIH for fiscal 2020 had encoded a cut of 12 percent over the previous fiscal year, but Congress reversed that, adding 6 percent to the tally for a total of $41.5 billion. The emphasis on increased NIH budgets was to some extent justified by the notion that increased funding is critical to sustain the U.S. lead in the life sciences, but the need to provide American patients with the latest therapies and diagnostics per the 21st Century Cures Act also fed the emphasis on larger NIH budgets.

In keeping with past budget proposals, the White House has floated an NIH budget of $38.7 billion, which tallies to a cut of roughly seven percent. That news was greeted with a letter of petition to Congress to override the budget proposal and increase the NIH budget to nearly $45 billion. This would represent a boost of $3 billion over the allocation for the current fiscal year and would allow for “meaningful growth above inflation.”

The Ad Hoc Group for Medical Research counts a number of medical professional societies among its membership, such as the American Colleges of Cardiology and Radiology, but also the American Cancer Society and a long list of academic research centers. In all, the letter enjoyed the support of more than 330 organizations.

One possible source of upward pressure on the NIH budget is an update to the 21st Century Cures Act, dubbed Cures 2.0. Rep. Fred Upton (R-Mich.) posted a discussion paper stating that Cures 2.0 is intended to modernize Medicare coverage of and access to the latest therapies, but Upton and Rep. Diana DeGette (D-Colo.) also emphasized digital health. While this document does not explicitly call out NIH funding, the first Cures bill carried a mandate to increase such funding, a mandate that will be difficult to resist, given the bipartisan appeal of greater funding for NIH.

That emphasis on digital health is likely to be used to push more funding for the FDA as well, which is still struggling with regulation of digital health. It might be noted as well that HHS Secretary Alex Azar lent the administration’s support to the latest drug pricing bill by Sens. Chuck Grassley (R-Iowa) and Ron Wyden (D-Ore.)

Analysis Sees Slight Increase for CDRH

The Alliance for a Stronger FDA posted a review of the likely impact of the budget proposal on the FDA, which indicates that the budget authorizations for the Center for Drugs and the Center for Biologics would both be level with FY 2020. The Center for Devices and Radiological Health would see an increase of $21 million under this proposal, up to $416 million, although the National Center for Toxicological Research would lose $1 million for a budget authority of $66 million.

Per the statutory authorities, the funding for 21st Century Cures activity at the FDA would drop from $75 million in FY 2020 to $70 million in the coming fiscal year. The Alliance based its assessment on one of the several documents posted by OMB, which indicates the FDA will receive $2.7 billion in user fees in FY 2021.

One significant change the budget proposal would impose upon the FDA would be to eliminate oversight of tobacco and related products. That proposal drew considerable blowback from a number of sectors, and would require that the Senate confirm the administrator of such an agency. Whether such a change would enhance federal government oversight of these products is unknown, but the American Heart Association was only one of several organizations that blasted the move. The AHA statement recommended that the Trump administration focus more on youth tobacco use and nicotine addiction, and on ensuring the FDA “exercises the authority it has been granted to protect public health.”

Breathing Room but Hefty Fines: NIH’s Final Rule for Study Registration

The National Institutes of Health has finalized the rule for registration of drug and device trials at clinicaltrials.gov, one of the most commercially important documents the agency has published in decades. While the NIH did relent on a couple of points essential to industry, it appears that the requirements will be retroactive, thus exposing device makers to a fine of $10,000 per day per violation for any studies that are not up to date regardless of when those studies first appeared at the clinical studies website.

The NIH notice of proposed rulemaking (NPRM) came to light in 2014, and the docket for this proposal drew more than 900 comments, some of which was reflective of a considerable amount of consternation by those in the life science industries. Among the concerns expressed by industry early on was that the draft rule would have forced the disclosure of confidential information that could compromise a drug or device maker’s competitive position. However, industry was not the only target of the rule. By some accounts, most of the failures to register a study are accounted for by researchers working on studies not sponsored by industry. In any case, members of the NIH team said in an article in the New England Journal of Medicine that only about 10% of the studies registered at clinicaltrials.gov include results data from the registered study.

The retroactive nature of the mandate suggests the FDA will be on the look-out for violations of the final rule by drug and device makers. There does seem to be a split on the question of Section 522 post-market surveillance studies, however. The NIH flowchart regarding clinical trial compliance under the Food and Drug Administration Amendments Act of 2007 – the law that gave rise to the NIH rule – suggests that Section 522 studies are only required to register at the NIH site if those studies are of devices in pediatric populations

Nonetheless, any laggardly performance in these non-pediatric Section 522 studies might show up on the FDA radar screen if the agency starts hearing from the public, or from Capitol Hill, about clinical trial compliance generally.

Makers of combination drug-device products were none too happy to see that the NIH draft had stated that trials of combination products would be treated as pharmaceutical agents for the purposes of trial registration. The NIH heard from a number of entities that the final rule ought to reflect the designation applied to the product by the FDA’s Office of Combination Products, which itself has come under a barrage of criticism of late. The final NIH rule conceded the point

On the point of disclosure of trade information, the NIH opted to give sponsors of clinical studies of unapproved drugs and devices a year after the study’s primary completion date to register the results of the study, although sponsors can avail themselves of an additional two years if they certify that they intend to continue development of the product in question. Disclosure of dead-end studies would be required upon the sponsor’s notification of abandonment of the study.

As for timelines, the NIH said the final rule goes into effect on Jan. 18, 2017, and that compliance will turn into enforcement three months later, on April 18, 2017. That leaves sponsors less than six months to determine which of their studies are subject to the final rule and get those studies’ data updated. After all, $10,000 per violation per day can add up quickly.