Potential False Results with Roche Molecular Systems’ SARS-CoV-2 Assay

Potential False Results with Roche Molecular Systems’ SARS-CoV-2 Assay

By Richard A. Lewis, Senior Regulatory Device & Biologics Expert

On Friday, March 12th FDA posted a letter to healthcare providers about performance concerns regarding the Roche Molecular Systems, Inc. cobas SARS-CoV-2 & Influenza Test for use on cobas Liat System.  This public letter appears to be the culmination of a dialogue between Roche and FDA.  Roche’s root cause analysis investigation has identified two potential causes for the false positives:

  • Roche identified that the assay tubes may sporadically leak, causing an obstructed optical path in the Liat analyzer, producing abnormal PCR growth curves. This could lead to invalid or erroneous positive results, particularly for the Flu B test. If a tube leak occurs, later testing runs may have an increased likelihood of false positive Flu B results.
  • Roche determined that abnormal PCR cycling in the reaction tubes may also produce abnormal PCR growth curves, leading to erroneous results. The issue is sporadic and may be caused by multiple factors happening at the same time, such as hardware positioning, volume movement, and curve interpretation. This issue may cause false positive results for multiple analytes (Influenza A, Influenza B and/or SARS-CoV-2) in a single testing run.

In response, FDA recommended three actions by users:

  1. Monitor for unexpected clusters of positive Flu B results, as this may indicate the cobas Liat System has experienced a tube leak.
  2. Repeat tests when two or three analytes are positive. Different results on the repeat test may indicate abnormal PCR cycling.
  3. Stop using the cobas Liat System and contact Roche if you suspect either of these two issues has occurred.

This letter is not the first FDA has posted for Clinical Laboratory and Point-of-Care staff.  It is actually the fourth one since October 2020 and the eighth such notice flagging in‑vitro diagnostic performance issues or concerns during the pandemic.

These notices have hit each of the three major classes of in-vitro diagnostic products used for the nation’s pandemic response, PCR, Serology, and Antigen Tests.  Here are three relatively recent examples:




The full list of FDA’s “Letters to Health Care Providers” can be found here.

As we proceed through this pandemic, it is becoming more critical that manufacturers be as vigilant as ever with post-market surveillance to flag performance issues early in order to be able to investigate and identify potential root causes.  Prompt investigation and correction is always preferable to pulling a test that works out of the marketplace.  It is in no one’s best interest to lose testing capacity and we hope that FDA is affording companies of all sizes the same opportunity that Roche has been given to investigate and correct rather than be forced to pull an assay from distribution.

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The Biden Admin Announces Expansion of COVID Testing with New Funding – “Living in a Material World”

The Biden Admin Announces Expansion of COVID Testing with New Funding – “Living in a Material World”

By Richard A. Lewis, Senior Regulatory Device & Biologics Expert

On February 17th, 2021 the Biden Administration announced an expansion of the Federal strategy to test the population for SARS-CoV-2 with a three pronged approach:

  1. Expand COVID-19 testing for schools and underserved populations ($650 Million);
  2. Ramp up the domestic manufacturing of testing supplies and raw materials ($815 Million); and
  3. Increase genomic sequencing of the virus to better prepare for the threat of variants ($200 Million).

Each of these goals requires significant and targeted investment at all levels of the diagnostics supply chain from testing locations to finished device manufacturers to the suppliers of raw materials.

The administration has set aside a total of $1.665 billion dollars across all three initiatives. The $650 million dollar investment into new testing is intended to translate into 25 million new tests delivered monthly to regional hubs across the US that are under the auspices of DoD and HHS.  It is not clear from the administration’s announcement what the total number of tests that are expected to be realized by this investment, but the news is still overwhelmingly positive for manufacturers still working their way through the EUA process. This initiative puts an emphasis on targeted testing of the population that will occur outside the traditional laboratory setting. This is consistent with a shift in FDA’s focus for diagnostic tests from CLIA Lab runs assays to non-laboratory sites such as Point-of-Care and Home Use. HPM recently released a blog post on FDA’s changing priorities (“Beware EUA Deprioritization”)

The lion’s share of the monies ($815 million) is slated for domestic manufacturing of testing materials.  Specifically, filtered pipette tips, nitrocellulose, and injection molded reagent container closures. This additional investment is heartening news as many manufacturers have experienced delays in device development over the last 12 months that are directly traceable to the ability to source samples, reagents, controls, and basic testing supplies.  The infusion of federal money toward domestic manufacturing may favor EUAs that bolster the domestic supply chain.

The final pool of monies ($200 million) is slated to address an ever-increasing concern for the pandemic which is the mutation of the SARS-CoV-2 virus and the rise in new mutant strains that may impede our march toward herd immunity and a return to normalcy. This increased funding for virus sequencing may aid in the rapid identification of new variants and allow for the development of multi-valent vaccines or boosters to maintain the efficacy of the vaccination program.  This money will likely not impact the EUA work that the Center for Devices and Radiological Health is doing in the review of new diagnostic EUAs.

This announcement comes amidst a series of public notices and statements from FDA regarding their concern with genetic mutations of the virus impeding the performance of diagnostic tests. On February 4th 2021, FDA provided a “Coronavirus (COVID-19) Update” where the agency stated:

For diagnostics, we have been monitoring for new mutations, identifying and working with developers of tests whose performance may be adversely impacted by them, and communicating with the public when helpful information becomes available. At this time, we believe the risk that the currently known mutations will impact overall testing accuracy of molecular tests is low. Moving forward, we are considering expanding the role of in silico monitoring by sponsors prior to and following authorization to assess for mutations that impact the performance of the test, test designs to minimize the impact of new mutations and ways to label authorized products to be transparent about what we know the test can detect.

This update was followed-up later in the month on February 22nd, 2021 with a new policy “Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests.”  With issuance of this policy statement, FDA is putting industry on notice that due to the rise of mutations, post-authorization monitoring of assay performance will be a key consideration for an EUA. In this policy FDA states:

During FDA’s review of an EUA request for a COVID-19 test, FDA intends to consider the performance of the test across all known variants, as well as the developer’s plans for post authorization monitoring.

For industry, the only way to keep up with new mutations is to run an analysis through a sequence database, like the one maintained by the National Center for Biotechnology Information (NCBI). It is expected that this increased funding will improve the quality of databases that are used to monitor the pandemic and that industry uses to evaluate inclusivity of their tests.

In this policy update, FDA also gives granular feedback to industry on FDA’s expectations for developers of molecular diagnostic tests. However, the feedback for developers of Serology and Antigen tests is high level with more feedback from the Agency being promised in future updates to the EUA templates.  In light of FDA’s policy, companies with pending EUAs or those who are in the process of preparing their submissions to FDA should be proactive and develop plans for the evaluation of mutations as FDA has applied new thinking and requirements retroactively to EUA reviews.

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When Is Skinny Not Skinny Enough?

When Is Skinny Not Skinny Enough?

By Sara W. Koblitz

Perhaps when you’re carving out a patented method of use?  Well, at least that’s what GSK is arguing.  As the now-infamous GSK v. Teva case makes its way through the Federal Circuit once again to address what many have called the death-knell to skinny-labeling (also called a “section viii statement” or a “carve-out”), Teva is poising for a fight to save the practice.  Framing the issue in the Petition for Rehearing briefing, Teva, like much of the generic industry, argues (with support from former Rep. Waxman) that the Federal Circuit decision upends the statutorily-enacted Hatch-Waxman carve-out.  GSK, on the other hand, characterizes the issue as a fact-specific inquiry into whether Teva’s generic carvedilol adequately carved out enough of a patented method-of-use included in GSK’s Reference Listed Drug (“RLD”) Coreg’s labeling.  The Federal Circuit reheard arguments on this case in February 2021.  And, as we wait for a new opinion that could have huge implications for generic drugs, we bring this (belated) update.

To jog your memory: In October 2020, the Federal Circuit issued a big blow to the generic drug industry when it reinstated a jury verdict awarding GSK $235 million in damages from Teva resulting from the generic company’s alleged “induced infringement” of a GSK patent through skinny-labeling.  As we explained back in October, the Hatch-Waxman Amendments permit generic drug companies to “carve-out” a patent-protected method-of-use included in the labeling of the RLD so long as such a carve-out does not compromise the safety or effectiveness of the product for the conditions of use remaining in the labeling.  The resulting “skinny-labeled” generic can still be listed in the Orange Book with an “A” therapeutic equivalence code because such ratings look only to the drug product itself rather than the approved indications.  As a result, a skinny-labeled “A”-rated generic drug can be, and indeed automatically will be, substituted for the brand drug regardless of the reason the product is prescribed.  Effectively, GSK argues, even though the statute provides for such a carve-out, even though FDA’s Orange Book states that the generic is therapeutically equivalent to GSK’s product, and even though the pharmacy is legally required to substitute an AB-rated generic for brands in most states (absent doctor’s orders otherwise), the mere truthful promotion of Teva’s skinny-labeled version of GSK’s Coreg (carvedilol) as AB-rated constitutes induce infringement.  And, for all intents and purposes, both the jury and the Federal Circuit agreed, making sweeping statements indicating to industry that even the carved-out label may be enough to induce infringement (“[p]recedent has recognized that the content of the product label is evidence of inducement to infringe”).

Understandably, the Federal Circuit decision led to a panic in the generic industry.  Skinny-labeling has been around for decades—countless generic drugs have marketed their skinny-labeled drugs as therapeutically equivalent to their Reference Listed Drug.  Now, even though some of those patents have expired and carved-out language added into the generic labeling, there’s no telling how many cases for induced infringement may be in the wings.  Given this uncertainty in the industry, many have expressed concern about whether generic drug sponsors will proceed with patent carve-outs and whether any resulting hesitancy will result in increased drug prices.

It is no surprise then that Teva promptly petitioned the Federal Circuit for a rehearing en banc.  Framing the issue as “whether induced infringement can be used to nullify a provision of the Hatch-Waxman Amendments,” Teva argued (as many in the press have) that if describing a skinny-labeled product as the generic equivalent of the RLD “can be inducement, as the majority held, every skinny-labeled generic is at risk, and the carve-out statute is a dead letter.”  GSK, on the other hand, opens its Response to Teva’s Petition with a strong statement: “This case does not implicate the fate of section viii carve-outs.”  Instead, GSK explains, that the case is much narrower than Teva portends as it “merely reaffirmed that section viii is not a get-out-of-jail-free card for generics who do not fully carve out the patented use from their labels.”  GSK explains that Teva did not thoroughly carve out all of GSK’s patented use, and it’s the label’s claims that induced infringement, not the AB-rating promotion.  GSK concedes that the Federal Circuit opinion never actually noted that the “partial label instructed the patented method,” but argues that “that finding is implicit in, and necessary to, its decision.”   

On February 9, 2021, the Federal Circuit vacated the October 2, 2020 judgment and withdrew the controversial opinion.  The Federal Circuit granted a panel rehearing (rather than en banc), which occurred on February 23, 2021.  But rather than address the overarching issue of induced infringement by way of skinny labeling, the Court limited the appeal—or at least the rehearing—to evidence to support the jury verdict of induced infringement.  In other words, the Court declined to address whether skinny-labeling itself is induced infringement and theoretically will look only to the specific promotion used to allegedly induce infringement.  This limitation could provide for a much narrower decision than the October 2, 2020 decision, but the Court did leave room for itself to make a broader decision, stating that “[w]e find all other issues to be sufficiently briefed.”

While FDA did not submit an Amicus Brief, Henry Waxman—the namesake of the legendary Hatch-Waxman Amendments that created the skinny-label practice—did.  Others joined Rep. Waxman in submitting Amicus Briefs, including Apotex, Novartis, Mylan, a consortium of professors, Knowledge Economy International, the Association for Accessible Medicines, and the R Street Institute in support of Teva.  These briefs focused on the policy aspects—health, economic, and patent policy.  No Amicus Briefs were filed in support of GSK or the Federal Circuit’s decision.

The Federal Circuit reheard the case on February 23, 2021.  From all accounts, the panel listened to the narrowed questions about the facts at issue here (i.e., whether Teva’s skinny-labeled carvedilol carved out enough language) rather than the overarching concerns about the death of the carve-out.  This makes sense given the parties and the venue: a patent case should be specific to the patents-at-issue, not a validation of a statutory provision.  However, we can’t help but think about the arguments that might arise if this case were strictly about statutory interpretation.  How would the Court reconcile the implicated conflict between the patent statutory scheme (induced infringement) and the Hatch-Waxman Act (carve-outs)?  Obviously, patent and FDA cases overlap often: innovation is critical to the drug industry and patents are critical to innovation, thus ANDA litigation, 30-month stays, etc.  But, effectively, this case would force the Courts to determine whether to protect innovation or whether to protect accessibility—the very balance that Congress sought to achieve in adopting the Hatch-Waxman Amendments.  Given the limited oral argument, it’s unlikely that the Federal Circuit will go that far in this case, as it will probably issue a very narrow decision that allows the skinny-label to live another day, but the Federal Circuit did leave room to address the entire issue.  But all we can do now is wait to see if the Federal Circuit believes that Teva’s carvedilol labeling was skinny enough or whether the Federal Circuit’s initial decision applies more broadly.

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If You Want It Done . . . Bill to Facilitate Marijuana and CBD Research Re-Introduced in the Senate

If You Want It Done . . . Bill to Facilitate Marijuana and CBD Research Re-Introduced in the Senate

By Larry K. Houck

The Senate recently reintroduced legislation that would promote research into medical use of marijuana.  The legislation would also importantly correct a deficiency in prior law and the Drug Enforcement Administration’s (“DEA’s”) recent rulemaking related to synthetically derived CBD.

Marijuana remains classified as a schedule I controlled substance under the federal Controlled Substances Act.  Because drugs in schedule I are defined to have “no currently accepted medical use in treatment in the United States,” distribution except in very limited circumstances of any product containing marijuana remains illegal at the federal level.  21 U.S.C. § 812(b)(1)(B).  To date, only certain drugs containing THC such as Marinol, and hemp-derived CBD with less than 0.3 percent delta-9-tetrahydrocannabinol (“THC”) have been excluded form Schedule I.  Yet despite federal law, 36 states and the District of Columbia have authorized the manufacture, distribution and use of marijuana and/or its constituents including THC and cannabidiol (“CBD”) for a wide-range of differing medical indications.

We reported in January how after more than four years DEA finally issued its final rule on registering additional manufacturers of marijuana for research.  (For our post, see The Long and Winding Road: DEA Issues Final Marijuana Registration Rule, Jan. 8, 2021.)  Congress, however, has not been sitting idly with respect to cannabis research.  Senators Dianne Feinstein (D-CA), Chuck Grassley (R-IA) and Brian Schatz (D-HI) re-introduced a bill with bipartisan support in the Senate that seeks to expand medical research with marijuana and CBD by removing some of the restrictive regulatory roadblocks.  The Senate unanimously passed an identical bill during the waning days of the last Congress.  Senator Feinstein, re-introducing the Cannabidiol and Marihuana [sic] Research Expansion Act on February 4th observed, “If the science shows that marijuana and its derivatives, including CBD can effectively treat serious medical illnesses, we should enable products containing these substances to be brought to the market with FDA approval.  But in order to make this determination, we must reduce the barriers currently impede important research.”  Feinstein, Grassley, Schatz Introduce Bill to Expand Cannabidiol, Marijuana Research, Press Release, Feb. 5, 2021.

The bill, S. 253, would promote cannabis research by requiring the Attorney General (by delegation, DEA) to register researchers if Health and Human Services (“HHS”), National Institutes of Health (“NIH”), or another federal agency that funds scientific research reviews and approves their research protocol and they employ adequate security measures to prevent diversion.  DEA would have to approve registration applications or request supplemental information within 60 days, then approve or deny registrations within 30 days after receiving supplemental information.

The bill would also expedite the process to increase the quantity of cannabis for research and facilitate protocol changes without requiring researchers to reapply.  Researchers seeking to increase drug quantities would only have to notify DEA instead of both DEA and FDA.  Researchers seeking to amend approved protocols involving changes to drug quantity or type, its source or storage, tracking or administration conditions must only notify DEA at least 30 days before implementation.  Their request would be deemed approved unless DEA objects within 30 days.  The agency can only object if additional security safeguards are required.  HHS would maintain authority over research protocols, including changes in administration, dosing and number of patients.  The bill requires DEA to issue regulations related to these changes within a year.

In addition to requiring DEA to process cannabis researcher applications within a certain timeframe, the bill imposes time constraints by when the agency must move on bulk marijuana manufacturer applications.  For bulk marijuana manufacturers, DEA would have to approve or request supplemental information for applications to manufacture for research solicited in the Federal Register within 60 days of receiving an application, then approve or deny the application within 30 days of receiving required supplemental information.  Requiring DEA to move on marijuana manufacturer applications is a welcome advancement of the registration process as some of the 38 marijuana manufacturer applications received by DEA lingered for four years after the agency announced that it would issue additional registrations in August 2016.

The bill streamlines development of FDA-approved drugs using marijuana and CBD by:

  • Allowing accredited universities and medical schools, practitioners and manufacturers with a schedule I registration to manufacture, distribute, dispense and possess marijuana for medical research aimed at drug development or commercial production;
  • Requiring DEA to license manufacturers and distributors for the commercial production of FDA-approved marijuana or CBD drugs; and
  • Allowing DEA-registered institutions to import or export marijuana or CBD to conduct medical research for drug development.

Within one year of enactment, HHS must report to Congress on potential therapeutic effects of marijuana and CBD on serious medical conditions, and their effects on the human body, the adolescent brain, and on cognitive abilities, including the ability to operate vehicles and heavy equipment.  HHS will also report on the research barriers of marijuana grown in states that have legalized its use, and recommend how to overcome them.

The bill would allow physicians to discuss the potential harm and benefits of marijuana derivatives like CBD, as treatment with patients.

The bill also corrects a non-sensical interpretation stated in DEA ‘s August 21, 2020 interim final rule that non-plant, synthetic CBD is a schedule I substance regardless of whether its THC content on a dry weight basis is at or below the 0.3% level for non-controlled hemp-derived CBD.  The bill would amend the definition of marijuana in the CSA to exclude the synthetic equivalent of hemp-derived CBD containing less than 0.3% THC.  It makes no sense to treat synthetic CBD as a schedule I controlled substance when its abuse potential, little as it may be, is less than hemp-derived CBD.  The bill would allow researchers and others to handle synthetic CBD without having to comply with DEA registration, recordkeeping and security requirements.

A number of organizations support the bill including the American Medical Association, American Academy of Pediatrics, American Society of Addiction Medicine, Friends of the National Institute on Drug Abuse, National Cannabis Industry Association and the National Organization for the Reform of Marijuana Laws.

The bill has been referred to the Committee on the Judiciary.

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Higher Medicaid Rebates Will Help to Fund COVID Rescue Plan

Higher Medicaid Rebates Will Help to Fund COVID Rescue Plan

By Alan M. Kirschenbaum & Michelle L. Butler

Last Thursday March 11, the American Rescue Plan Act of 2021 was signed by President Biden.

Out of the hundreds of pages of this COVID relief legislation, our pinpoint focus here is on several pages relating to Medicaid coverage and drug rebates.  The legislation requires Medicaid and the Children’s Health Insurance Program (CHIP) to cover COVID-19 vaccines, vaccine administration, testing, and treatments, without cost sharing, for all eligible beneficiaries during the public health emergency and for one year after it ends.  Sec. 9811(a)(1), (2).  The legislation also makes clear that COVID therapies and preventive measures are subject to rebates under the Medicaid Drug Rebate Program if they are “covered outpatient drugs” as defined in the Medicaid Drug Rebate statute.  Sec. 9811(a)(4).  As with other vaccines, COVID-19 vaccines remain excluded from the Medicaid Drug Rebate Program.  Sec. 9811(a)(4).

A question arises whether an unapproved drug authorized under an emergency use authorization (EUA) is a covered outpatient drug subject to Medicaid rebates.  Under a literal reading of the definition of a covered outpatient drug, such a drug must be approved under section 505 or 506 of the FDC Act or section 351 of the Public Health Service Act.  An EUA is authorized under section 564 of the FDC Act and is not an approval pursuant to those provisions.  However, in a somewhat related context, CMS has suggested that an EUA is an “approval” under the FDC Act.  COVID-19 Frequently Asked Questions (FAQs) for State Medicaid and Children’s Health Insurance Program (CHIP) Agencies, p.18, fn. 3.   Hopefully CMS will provide guidance on this point.

Of broader consequence to drug manufacturers generally, effective January 1, 2024, the legislation sunsets the cap on the total Medicaid unit rebate amount that was instituted by the Affordable Care Act.  Sec. 9816.  (The House version of the bill had this change taking effect January 1, 2023, but the effective date for the change was extended by one year by the Senate.)  The total calculated Medicaid rebate amount is comprised of the basic rebate and the additional rebate, which is a penalty imposed for raising a price at a rate greater than the rate of inflation.  Without a cap, the rebate can be more than the average manufacturer price (AMP) of the drug.  The Affordable Care Act capped the rebate at 100% of the AMP so that a manufacturer would not pay a higher rebate for a drug than its AMP.  According to the House Report, CBO estimates that eliminating this cap will increase the amount of rebates that manufacturers pay Medicaid and will reduce direct spending in Medicaid by $15.9 billion over the 2021-2030 period.

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Keeping Up With the Kardashians – OPDP Edition

Keeping Up With the Kardashians – OPDP Edition

By Dara Katcher Levy

I would be lying if I said I hadn’t expected this most recent OPDP Untitled letter.  OK, maybe not THIS letter.  Some background: Back in November 2020, after an article was published about the ethical questions surrounding “Sponcon,” (sponsored content – for those not hip to the lingo), I pulled up Khloe Kardashian’s Twitter feed to check out her recent ad for Nurtec ODT.  I stared at the ad, and then spent an embarrassingly long amount of time debating with myself as to whether placing scrolling ISI right below Khloe Kardashian’s bust made it more OR less likely to be noticed.  I passed my phone to my husband and asked him to tell me about the Nurtec ODT safety information.  Eyes glazed, he responded, “there’s safety information?”  I had my answer.

This most recent OPDP letter (the first Untitled Letter of 2021), objects to a sponsored video – and is similar to OPDP’s last Warning Letter to CooperSurgical.  Parallels between the two letters include the offending material being a sponsored video (not otherwise re-distributed by the company on different platforms), no Form 2253 submission, and complaints lodged through FDA’s Bad Ad program.

This letter is significant for a number of reasons (not the least of which is that I now can’t simply refer to the “Kardashian Letter” as it may create confusion about which letter I’m referencing).  What’s fascinating (to me) is that OPDP includes in second place its allegations that risks were minimized in the video, prioritizing the offending efficacy claims.  And what are those efficacy claims?  The first of which is that Nurtec ODT “works in about 15-30 minutes.”   The second is that Nurtec ODT was a “gamechanger” and “other medications would give me rebound headaches, and this one doesn’t . . .”

In 2012, an Untitled Letter based on these claims would be expected.  But in 2021, given the significant drop in OPDP enforcement letters and post publication of FDA’s Guidance on Medical Communications Consistent with the FDA-Required Labeling (Guidance), are these the type of claims to trigger an OPDP Untitled Letter?  The claims, themselves, seem awfully similar to specific examples FDA includes in its Guidance, which permits product communications consistent with the FDA-required labeling even if those communications are not based on substantial evidence.  From the FDA Guidance:

Q.4.        What are examples of the kinds of information that could be consistent with the FDA-required labeling for a product?

A.4.        The following are examples of some general types of information that could be consistent with the FDA-required labeling. . . Information based on a comparison of the safety or efficacy of a medical product for its approved indication to another medical product approved for the same indication . . . Information about the onset of action of the product for its approved indication and dosing/use regimen (e.g., the FDA-required labeling for a product approved to treat major depressive disorder does not contain information about onset of action before the point in time designated as the study’s endpoint, and a firm’s product communication provides information indicating that the product shows an effect relative to the control at 2 weeks).

So what happened here?  What happened seems to be the absence of any evidence to support Ms. Kardashian’s claims other than her personal experience.  Consistency with the FDA-required labeling is not the only factor to consider when determining whether a communication is truthful and non-misleading.   Claims must still be supported by evidence that is scientifically appropriate and statistically sound.  “The amount and type of evidence needed to support a particular CFL promotional communication depends in part on the topic addressed by the communication. For example, different evidence would be needed to support a long-term efficacy presentation than would be needed to support a presentation about a product’s mechanism of action. The amount and type of evidence needed also depends on the particular representations or suggestions that are made about any given topic in the communication.”  Guidance at 12.  Therefore, despite these claims representing a truthful experience for Ms. Kardashian, the letter points out that they are misleading because OPDP is unaware of any data that supports these statements, generally.

OPDP further cites the video as misleading “because it fails to present information relating to the contraindications, warnings, precautions, and adverse reactions for Nurtec ODT with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of Nurtec ODT. Specifically, the video contains claims and/or representations about the benefits of Nurtec ODT in the audio portion, while the risk information is presented in text only format and in small font. Moreover, the risk information only appears briefly for four seconds at the end of the video, after the close of the Spokesperson’s presentation, where it is unlikely to draw the viewer’s attention.”   OPDP’s views as expressed in this letter are not new; 21 C.F.R. §202.1(e)(1) provides that advertisements broadcast through media such as radio or television include information relating to the major side effects in the audio or audio and visual parts of the presentation.  It is not sufficient to have safety information presented solely on screen when efficacy is provided through audio.   Content and format considerations with regard to presenting risk information in broadcast promotional material has been an issue reiterated in FDA’s (Draft) Guidance on Presenting Risk Information and has also been the subject of OPDP research.

Circling back to initial perceptions about the similarities between this Untitled Letter and the recent CooperSurgical  Warning Letter, it’s notable that both relate to TV broadcast videos that were “sponsored” by the company, not re-distributed on other platforms, and not submitted to FDA on Form 2253.  With the increasing number of television shows that allow third parties to sponsor content, industry should be particularly cautious when availing itself of these opportunities.  Depending on the context, interviews with your spokespeople and sponsored TV/News segments about your products may subject you to liability even if you are not in complete control over the content and do not otherwise re-distribute it.

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FDA Warns Against Use of Registration Certificates: It Don’t Mean A Thing

FDA Warns Against Use of Registration Certificates: It Don’t Mean A Thing

By Anne K. Walsh

It’s not just drug companies that push the limit on marketing their products – see our posts about recent OPDP warning letters.  Medical device companies are fighting for any edge to differentiate their products too.  Even before COVID-19 brought an onslaught of new players to the FDA-regulated space, many sophisticated medical device companies used to include FDA’s logo on marketing materials to imply that FDA had endorsed their products.  The misuse of the logo became so pervasive that FDA issued an official “FDA Logo Policy,” which warns that “[u]nauthorized use of the FDA logo may violate federal law and subject those responsible to civil and/or criminal liability.”  Despite this threat, FDA continues to cite companies for misuse of the logo.  See, e g., Warning Letter issued to Silkprousa LLC (Aug. 18, 2020) (“Your device is also misbranded under section 502(a) of the Act, 21 U.S.C. § 352(a), because your labeling on the package of your device and your website uses the FDA logo.  The FDA logo is for the official use of the FDA and not for use on private sector materials.”).

The COVID-19 pandemic has caused companies to exercise even more creative license in an attempt to differentiate products that might otherwise appear interchangeable (e.g., 3-ply disposable face masks).  We have seen the advent of the “FDA Registration Certificate,” which looks like an official government document, and sometimes includes the FDA logo (illegal by itself), the establishment registration number, or a screenshot of the FDA establishment registration database showing the company’s registration status.  Any savvy FDA lawyer knows that registration alone does not convey information about the company or product’s regulatory compliance status, and certainly does not imply FDA approval or endorsement of a product, but not all of us can be savvy FDA lawyers.

On March 3, 2021, FDA announced that it had told 25 companies that produce these so-called “FDA Registration Certificates” to stop issuing them.  We have not yet seen the letters FDA issued to the certificate-producing companies, and it’s unclear whether FDA will follow-up with enforcement action if these companies fail to cease distribution of these documents (and if so, on what grounds).

In conjunction, FDA released a new webpage titled “Are There ‘FDA Registered’ or ‘FDA Certified’ Medical Devices?  How Do I Know What is FDA Approved?”  Spoiler alert: the answer to the first question is No. The key points FDA highlights are:

  • When a facility registers its establishment and lists its devices, the resulting entry in the FDA’s registration and listing database does not denote approval, clearance, or authorization of that facility or its medical devices.
  • The FDA does not issue any type of device registration certificates to medical device facilities.
  • Firms that misleadingly display certificates alongside information about and photos of a device for sale in the United States to imply review or approval by FDA of the device misbrand the device in violation of the Federal Food, Drug, and Cosmetic Act.

FDA also provided detailed directions for identifying a product’s status – whether it has been approved or cleared, or authorized under an Emergency Use Authorization.  Circling back to the grammatically curious title of this blog post, FDA’s point is that registration “don’t mean a thing” “if it ain’t got that” 510(k) clearance, PMA approval, de novo classification or EUA authorization – not as catchy as when Ella Fitzgerald and Duke Ellington sing it.

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HP&M’s Food, Beverage & Supplement Wrap Up: February 2021

HP&M’s Food, Beverage & Supplement Wrap Up: February 2021

By Karin F.R. Moore & Ricardo Carvajal & Riëtte van Laack

Welcome to the latest edition of Hyman, Phelps & McNamara, P.C.’s monthly wrap up of food, beverage and supplement news, including regulations, guidances, events, and whatever else is catching our eye.

Food & Beverage

  • Transition: As of this writing, Janet Woodcock is Acting Commissioner of Food and Drugs; Norris Cochran is Acting Secretary of Health & Human Services; and Tom Vilsack was just confirmed as Secretary of Agriculture (again!).
  • 3D printed ribeye? An Israeli company unveiled what is being described as a “3-D printed rib-eye” made with  “3-D bioprinting technology.” The company claims to have been in discussions with USDA and FDA for the past two and a half years.
  • Food Supply Chain Focus at the WH. The President signed an Executive Order to help create more resilient and secure supply chains for critical and essential goods, and agricultural commodities and food production are a key sector that will be the focus of a year-long review.
  • Keep those essential workers safe! FDA published a new web page with information to help employees in the food and ag sector communicate about COVID-19 vaccines in their workplace.
  • Prop 65: OEHHA announced a (virtual) public hearing on March 11, 2021, at 10:00 a.m. and extended the time for submitting comments to the proposed rule regarding short form warnings to March 29 to accommodate the hearing.
  • Baby food report. The House Subcommittee on Economic and Consumer Policy, Committee on Oversight and Reform released a report alleging “dangerous” levels of heavy metals in baby foods. Shortly thereafter, FDA published a response in the form of a Constituent Update in which the agency assured the public that “FDA regulations and monitoring help to ensure the safety of baby foods sold or manufactured in the United States.”
  • US Food Supply is Safe! FDA and USDA issued a statement that food and food packaging have not been linked to spread of COVID-19.
  • Costs of Foodborne Illness: USDA published a report on the cost of foodborne illnesses; the report is a bit short on conclusions but the cost continues to increase. This is not particularly surprising since last year CDC reported a continued increase in incidence of foodborne diseases.
  • Speaking of Pathogens in Food: Center for Science in the Public Interest together with several other public interest organizations and individuals submitted a petition to FSIS/USDA requesting that FSIS engage in rulemaking to 1) establish enforceable finished product standards for Salmonella types of greatest public health concern and Campylobacter and 2) require poultry establishments to identify and control food safety risks within their supply chain. FSIS opened a docket on regulations.gov for comments which must be submitted by April 6, 2021.
  • Organic wild caught fish? NOP just announced a town hall meeting regarding wild caught fish.


  • More transition. Steven Tave is leaving the Office of Dietary Supplement Programs and moving to the Office of Regulatory Affairs at FDA.  Cara Welch will be acting director of ODSP starting March 15.
  • Warning Letters. FDA issued warning letters to 10 companies for selling dietary supplements that claim to treat depression and other mental health disorders.
  • Criminal Sentencing. A former dietary supplement company executive was sentenced to prison for his role in fraudulently selling popular workout supplements that caused liver damage.  A number of executives have already been sentenced in this ongoing fraud investigation.
  • Nanotech-related claim requires substantiation. NAD recommended discontinuation of a claim touting a nanotech oral delivery system for glutathione as the first effective alternative to injections. NAD found the supporting in vitro and in vivo pilot studies did not constitute a reasonable basis for the claim.

More on Cannabis

Coming up:

  • The deadline for submission of comments on labeling of cell-cultured seafood products is coming up on March 8.
  • The American Conference Institute’s popular “FDA Boot Camp” – now in its 36th iteration – is scheduled to take place (virtually, of course) March 24-25, 2021, and is co-chaired by HPM’s own Kurt Karst.
  • Riëtte van Laack will be discussing “Nutrient Content, Health and Other Claims” at FDLI’s Introduction to Food Law and Regulation, March 16-18.


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Area of Interest Funding – “There’s Always Money in the Banana Stand”

Area of Interest Funding – “There’s Always Money in the Banana Stand”

By Richard A. Lewis, Senior Regulatory Device & Biologics Expert

If you tuned in to FDA’s weekly Virtual Town Hall Meeting on February 10th, 2021 you would have seen a short presentation by Toby Lowe (CDRH/OHT-7) describing a recent funding announcement from HHS OASH, Office of Assistant Secretary for Health, and the DoD. This “Area of Interest” (AOI) funding announcement is a call for proposals from industry.

you may request investment funding for capacity expansion and provide price quotes for raw materials, test components, supplies, et cetera for COVID-19 point-of-care tests and other IVDs. This is an expedited process that’s coordinated by HHS and OASH and DoD to support the government’s COVID-19 response to rapidly increase manufacturing capabilities within the diagnostic supply chain.

This funding announcement is not a unique occurrence, in fact, there is a whole group at HHS with a mandate to expand testing supplies and testing capacity through targeted investments.  The COVID-19 Testing and Diagnostic Working Group (TDWG) has been built around four central goals:

  • Understand the diagnostic supply chain, including projected production and potential constraints and bottlenecks;

  • Work with state public health and laboratory leadership, diagnostics manufacturers, and commercial labs throughout the country;

  • Provide technical assistance to leverage existing testing infrastructure and resources based on available tests; and

  • Distribute certain testing supplies, focusing primarily on point-of-care technologies, to support states’ testing goals.

This funding announcement is yet another indication, in a string of recent public statements and actions on the part of FDA, that the federal government is shifting time, energy, and resources from the CLIA Lab base testing to testing in non-laboratory settings, like Point-of-Care and people’s homes.  HPM recently released a blog post on FDA’s changing priorities (“Beware EUA Deprioritization”).

A link to the funding announcement can be found here.  The deadline to apply is March 7th.  (And for those Arrested Development fans, we’ll end with a link to the Banana Stand.)

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OPDP Issues Second Warning Letter of 2021. But Wait, Where Did the OPDP Warning Letters Go?

OPDP Issues Second Warning Letter of 2021. But Wait, Where Did the OPDP Warning Letters Go?

By Dara Katcher Levy

Well, it’s been busy for OPDP (and the Rx Ad/Promo bloggers over at the FDA Law Blog).  After getting off to a slow start in 2021, OPDP issued yet another Warning Letter, apparently the day after its first.  Unlike the first letter, this OPDP Warning Letter to CooperSurgical appeared “quietly” on FDA’s general Warning Letters page, and without the accompanying fanfare of a CDER press release and Twitter campaign (as we blogged about previously).  When checking the status of OPDP’s Warning Letters page, we were surprised (shocked, really) to see that all Warning Letters had been removed and the page had been updated to reflect only Untitled Letters.  We’re not happy with this development – having OPDP letters in a single location was incredibly useful when evaluating enforcement trends.

This newest Warning Letter about a video for Paragard (intrauterine copper contraceptive), ticks off several OPDP priority boxes – the product has a broad patient base with a video (airing on TV) that could be considered a wide-reaching promotional campaign, CooperSurgical was the subject of a previous OPDP letter for similar product promotion, and the video was brought to OPDP’s attention through the FDA Bad Ad program.

The offending video, entitled “Paragard: Family Planning During The Pandemic,” is no longer available, but appeared on WBTS’s The Hub Today, a Boston lifestyle and entertainment show.  FDA states that CooperSurgical failed to submit a copy of the video at the time of initial dissemination under cover of Form FDA-2253, and FDA’s description of the issues is short and to the point.  The video is described as providing claims and representations about the uses and benefits of Paragard, but failing “to communicate any risk information about the product.”  FDA specifically notes that referring viewers to the product specific website for further information did not mitigate the “complete omission” of risk information from the video.

CooperSurgical previously received an Untitled Letter in 2019 for a Paragard DTC TV advertisement for omitting important risk information.  OPDP so notes in this letter, stating that the new video appears to promote Paragard without presenting the serious risks in truthful and non-misleading manner, “despite concerns previously expressed by OPDP.”    The 2019 TV ad had also been reported to FDA under the FDA Bad Ad Program.

It’s likely OPDP may have been moved to issue the Warning Letter because of the perception that the sponsor did not address FDA’s objections to the previous video in the new one.  Rather than making the safety information more thorough, the new video seems to omit even more risk information.  Another factor may have been the large viewing audience that may have seen the video, which was broadcast on television.  This may also make the corrective communication FDA requests in the Warning Letter more challenging.

What is interesting and difficult to discern is whether CooperSurgical considered the video to be Paragard “promotion” and whether CooperSurgical had full control over the content of the video.  While the video is no longer available, OPDP describes the original broadcast on the lifestyle and entertainment show as promotional material that included the statement “sponsored by PARAGARD.”  Contrast this with OPDP’s 2019 Untitled Letter to Aclaris about a video interview that was broadcast on ABC’s The View, where OPDP cited the video as promotion and included reference to Aclaris’s Form 2253 submission, as well as the company’s re-posting of the video on the Eskata Facebook page and Aclaris LinkedIn page.  While industry may sponsor certain scientific and educational activities and not have those activities considered product promotion, there are guardrails, and DTC TV videos likely fall outside of them.   And, company intent about whether material is product “promotion” may ultimately be irrelevant to FDA’s determination.

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