The PREP Act and the Revocation of an Emergency Use Authorization

In recent weeks, the FDA has revoked Emergency Use Authorizations (EUAs) for several products meant to combat COVID-19.  These include the June 15, 2020 revocation [fda.gov] of the oral formulations of chloroquine phosphate and hydroxychloroquine sulfate and the June 16, 2020 revocation [fda.gov] of the Chembio Diagnostic Systems Inc.’s DPP COVID-19 IgM/IgG System.

The fact that FDA is revoking its authorization for drugs and medical devices may have implications for the immunity granted under the Public Readiness and Emergency Preparedness Act (“PREP Act”) (42 U.S.C. § 247d-6d and 6e) for products that have had their authorizations revoked.  This blog explores this issue.

Background on PREP Act and the EUA Statute.

Some background on both the PREP Act and EUA statute is important in order to understand the issue.  The PREP Act provides nearly blanket immunity under certain circumstances for manufacturers, distributors, and administrators of certain drugs, medical devices, and biologics meant to counteract an epidemic or pandemic.  This immunity is provided not only to approved drugs and cleared medical devices, but also investigational drugs and medical devices, as well as drugs and medical devices that have been authorized by the FDA under its EUA authority.

So, what is the FDA’s EUA authority and how does it work?  In short, if the Secretary of Health and Human Services declares a public health emergency, the FDA can authorize the use of a non-approved/non-cleared product, or authorize an off-label use of an otherwise approved/cleared product, for the limited purpose of combatting the public health emergency.  21 U.S.C. § 360bbb-3.  Once authorized for emergency use, the products can be sold and used under the conditions of the EUA authorization until one of three events occur: either (i) the product becomes approved or cleared via a traditional pathway, (ii) the public health emergency ends, or (iii) the FDA revokes its emergency use authorization.  Id.  The FDA can revoke an authorization if there is no longer a need for the product, the evidence supporting the authorization is no longer met, or other circumstances make revocation appropriate to protect public health and safety.  Id. at (g)(2).  Even if the health emergency ends or the FDA revokes its authorization, continued use of the product with respect to a specific patient can continue if found necessary by the patient’s attending physician.  Id. at (f)(2).

The EUA statute partially addresses the issue of a manufacturers’ obligations if the product is revoked or the public health emergency ends.  If the public health emergency ends, the EUA statute provides that the “Secretary shall consult with the manufacturer of such product with respect to the appropriate disposition of the product.”  Id. at (b)(2)(B).  The statute does not address this issue if the FDA revokes its authorization, though the FDA’s interpretation of the statute is that it will similarly consult with the manufacturer if it revokes the authorization on the appropriate disposition of the product.  Emergency Use Authorization of Medical Products and Related Authorities, Food Drug Cosm. L. Rep. 300052.

FDA’s COVID-19 Response.

With this background on the statutes out of the way, let’s turn to the FDA’s response to COVID-19 under these statutes.  On February 4, 2020, Secretary Azar declared a public health emergency for COVID-19, which enabled the FDA to begin issuing EUAs for products intended to combat COVID-19.  85 FR 7316.  Since the beginning of the COVID-19 pandemic, the FDA has authorized [fda.gov] over 150 products under its EUA authority.  These products fall into six categories: (i) In Vitro Diagnostic Products, (ii) High Complexity Molecular-Based Laboratory Developed Tests, (iii) SARS-CoV-2 Antibody Tests, (iv) Personal Protective Equipment and Related Devices, (v) Ventilators and Other Medical Devices, and (vi) Drug Products.

These 150+ products, as such, fall within the definition of a “covered countermeasure” under the PREP Act, and thus largely fall within the protections of the PREP Act.  42 U.S.C. § 247d-6d; see also 85 FR 15198.  However, the question arises whether the products for which EUA authority was revoked enjoy the same immunity as non-revoked EUA products under the PREP Act.

What Happens Under the PREP Act if the FDA Revokes its EUA Authorization?

Neither the PREP Act itself nor the EUA statute directly address the issue of what happens under the PREP Act if the FDA revokes its EUA authorization.  However, buried deep in the PREP Act are two references to EUA revocation.  These references strongly suggest that EUA revocation does not, in and of itself, remove PREP Act immunity.

The references to EUA revocation in the PREP Act appear in the section that addresses the willful misconduct exception to immunity.  As background, the PREP Act contains an immunity exception that provides that there is no immunity when a manufacturer or distributor engaged in “willful misconduct” with respect to the covered product.  In turn, the statute provides a lengthy definition of what constitutes willful misconduct.  42 U.S.C. § 247d-6d(c-d).  Among the circumstances described, is the initiation of an “enforcement action” by the federal government that resulted in a “covered remedy.”  Id. at (c)(5).  An “enforcement action” is defined as a laundry list of items, such as an injunction or mandatory recall of a product.  Among the listed items that constitute an enforcement action is “a revocation, based on willful misconduct, of an authorization under section 564 of such Act [21 USCS § 360bbb-3].”  Id. at (c)(5)(B)(i) (block parentheticals in original).  In other words, only a revocation of an EUA that was “based on willful misconduct” can constitute an “enforcement action.”  Id.  Conversely, in the laundry list of items included in the definition of “covered remedy,” the following appears, among others: “a revocation of an authorization under section 564 of such Act [21 USCS § 360bbb-3].”  Id. at (c)(5)(B)(i)(I) (block parentheticals in original).

As such, the PREP Act contemplates that a product whose authorization has been revoked for a reason other than willful misconduct – perhaps because FDA finds that there are significant clinical performance problems with it – is still entitled to immunity.  Otherwise, there would be no reason to define the method by which the authorization must be revoked in order to lose immunity.  A plaintiff attempting to demonstrate that PREP Act immunity does not apply needs to show more than just the EUA revocation in order to prove willful misconduct.  Rather, the plaintiff must show that the revocation was “based on willful misconduct” as defined in the Act.  Id. at (c)(5)(B)(i).  The recent revocation letters from the FDA contain no such language.

This conclusion that immunity remains following the revocation of an EUA is bolstered by the purpose of the PREP Act.  The policy behind the PREP Act is to provide immunity so as to encourage companies to make products that help reduce the severity of pandemics.  And, if all that must occur for a product to no longer receive the PREP Act protection is that it loses its EUA authorization status, that would run contrary to the purpose of encouraging companies to make products and seek EUA authorization.  Similarly, a product can lose its authorization once the pandemic is over in the same manner as if it was revoked during the pandemic.  And certainly, products that are no longer needed after the declared public health emergency has ended continue to have protection under the PREP Act for their use during the pandemic.  Otherwise, the PREP Act would provide no protection at all.

This conclusion is further bolstered by the fact that the PREP Act states that its “sole exception to the immunity from suit” is for “willful misconduct,” Id. at (d), which is a much higher standard than the standard for revoking an EUA.  Compare 42 U.S.C. § 247d-6d(c) (setting forth the willful misconduct standard) with 21 USCS § 360bbb-3(g)(2) (setting forth the revocation standard). While the “sole exception” language should not lull manufacturers into believing the PREP Act always provides protections, this “sole exception” language does show that willful conduct is far more serious than a simple revocation of an EUA.

In spite of the foregoing, none of the above points are a guarantee that a court may not reach a contrary result.  After all, the PREP Act does not specifically say that it extends to products whose EUAs have been revoked.  Rather, this is only a result by necessary implication from the definition of willful misconduct, as well as the policy behind the PREP Act and the EUA statute.

Next Steps After Revocation.

If an EUA is revoked, the manufacturer should work with FDA on the appropriate disposition of the product.  See 21 U.S.C. § 360bbb-3(b)(2)(B); Emergency Use Authorization of Medical Products and Related Authorities, Food Drug Cosm. L. Rep.  300052.  While the product can continue to be used for a specific patient if found necessary by the patient’s attending physician, what must be done with the product that remains in the marketplace after the EUA has been revoked needs to be addressed with FDA.

It is important for the manufacturer to be aware that in the laundry list of actions that constitutes “an enforcement action” under the PREP Act’s willful exception is “a mandatory recall of a product because [a] voluntary recall was refused.”  Put another way, if forced to do a mandatory recall as opposed to a voluntary recall, a manufacturer increases the likelihood that it will not enjoy the full protections of the PREP Act.

Written by Jordan Lipp, Partner at Childs McCune

Biosimilars, Biostatisticians, and the New EEU

There are very few days during which the worlds of drugs and medical devices are entirely quiescent, thanks to very active American courts and international regulatory churn. There is some good news in all this, but how good is it?

If you’re in the biosimilars business, the latest news is quite good, indeed.

SCOTUS rules for Sandoz

The U.S. Supreme Court ruled on June 12 that makers of biosimilars do not have to wait six months after the issuance of a biologics license application to begin marketing that product, a development that could bring some less costly biotech drugs to market more quickly and possibly take a bite out of spending on these agents.

In a 9-0 vote, the Court ruled in favor of Sandoz in Sandoz v. Amgen, a case that made a stop at the Court of Appeals for the Federal Circuit, where the outcome was quite different. Sandoz had argued that the terms of the Biologics Price Competition and Innovation Act of 2009 had essentially worked to add half a year of exclusivity to the 12 years already granted by the statute, and by some accounts, Sandoz’s Zarxio is about 15 percent less expensive than Amgen’s Neupogen, a drug for chemotherapy-induced neutropenia.

The news might not change the field dramatically in the near term, given that the FDA has approved only about half a dozen biosimilars to date, but one possible candidate for a quick entry to market is an oncology biosimilar for Avastin, which will undergo an FDA advisory committee review in mid-July. In an ironic twist, Amgen teamed up with Allergan to produce this biosimilar.

Expert witness refuted in Zoloft lawsuit

Pfizer scored a victory in the running lawsuit pertaining to the company’s flagship antidepressant Zoloft, but what may have been the most interesting part of this story is that a court rejected expert testimony relating to allegations that the selective serotonin reuptake inhibitor (SSRI) causes congenital heart defects.

The decision may have brought to a close an effort by more than 300 litigants, which absorbed a second consecutive negative outcome in the U.S. Court of Appeals for the Third Circuit. Both the appeals court and a district court decreed that the expert witness, Nicholas Jewell, a biostatistician at the University of California at Berkeley, had failed to plausibly link the drug to the birth defects. Among the problems with Jewell’s presentation is that he had rejected meta-analyses he had previously cited in a separate lawsuit pertaining to another SSRI.

Whether the plaintiffs will take this lawsuit any further is difficult to forecast, but a footnote on page 10 of the Appeals Court decision remarked that the plaintiffs’ attorneys had conceded that they are “unable to establish general causation” if the courts jettisoned Jewell’s testimony. Summary judgment was granted in favor of Pfizer.

This is not the only multi-district litigation keeping attorneys at Pfizer busy, however. A very active set of lawsuits dealing with proton pump inhibitors and purportedly associated kidney damage would seem to implicate the OTC version of Nexium, marketing rights for which Pfizer picked up five years ago in a deal with AstraZeneca. The U.S. Judicial Panel on Multidistrict Litigation (JPML) declined in January to consolidate these lawsuits, but another motion for consolidation has been filed by attorneys with Seeger Weiss of New York.

Regulations, regulatory agreements on the move

Efforts to ramp up medical device regulatory schemes in outside-U.S. jurisdictions are nothing new, but device makers can add Malaysia and the Eurasian Economic Union (EEU) to the list of national and international entities diving into deeper regulatory waters. The news for device makers is somewhat mixed, but greater clarity alone is sometimes enough to overcome other considerations.

First, Malaysia’s Medical Device Authority has declared that adverse events associated with medical devices will have to be reported to the agency within 30 days. This apparently applies to all devices that are on the Malaysian market, regardless of where the adverse event took place. Any fatalities have to be reported within 10 days, and device makers have a mere 48 hours to advise the agency of any problems that might carry a public health consideration.

The EEU continues to work toward a single market for drugs and devices, a move which if successful would capture the markets of Russia and four other nations for a total 2015 population of nearly 184 million. There are reports that Tehran is interested in a free trade agreement with the EEU, although there is no indication that Iran would take part this new med tech regulatory bloc despite the deepening geopolitical ties with Moscow. Serbia is likewise said to be interested in doing business with the EEU, but it’s not clear whether Belgrade has full-blown membership in mind, either, although the protracted and difficult negotiations for entry into the European Union might strike some as suggestive.

To date, the EEU regulatory regime lacks several critical documents, such as a framework for quality management systems. Registration requirements for this international regulatory system would be phased in over the next four years, however, giving industry a little breathing room for offerings already available in this market.