The COVID-19 pandemic has affected the U.S. FDA on the postmarket side as well as on the premarket side, but the focus of pandemic-driven warning letters has shifted over time. Amanda Johnston, senior attorney at Gardner Law of Stillwater, Minn., said on a Nov. 5 webinar the FDA’s emphasis lately has been closer to the agency’s traditional enforcement considerations after an initial wave of warnings dealing with flatly fraudulent products.
The FDA launched Operation Quack Hack in March 2020, in an effort to corral the scams that quickly surfaced as the COVID-19 pandemic unfurled, although the Federal Trade Commission has also engaged in related enforcement activities. Operation Quack Hack has identified more than 1,100 fraudulent products and unproven products since March, and has led to the issuance of nearly 130 warning letters. Johnston said the early emphasis was on the more egregious violations, an example of which is the April 8 warning letter to Genesis Church for its promotion of a chlorine dioxide treatment for COVID-19. The organization was marketing the product as Miracle Mineral Solution despite that the substance is commonly used for its bleaching properties.
In contrast, the Oct. 5 warning letter to Physician 360 Inc., of Southlake, Texas, cited the company for marketing three rapid diagnostic tests, one each for COVID-19, flu and streptococcus. The agency said it was not aware of any authorized, cleared or approved tests for home use for detection of flu and strep, although the company had made the case that these tests incorporated tests that already were cleared under the 510(k) program. The agency had little to say about the COVID test advertised at the Physician 360 website other than that it had not been reviewed under any of the agency’s authorities, however.
‘Confusing patchwork’ of individual, umbrella EUAs
Johnston pointed out that despite the flurry of FDA activity in connection with emergency use authorizations (EUAs), the agency will not grant this type of authorization for any product that is already on the market via the conventional premarket channels. One exception to this is when there is a shortage of the product, hence the EUAs for items such as surgical masks and ventilators.
Johnston pointed out that the volume of EUAs – and the subsequent modifications of each – has created “a confusing patchwork” of authorizations. The agency has issued both manufacturer/product specific EUAs along with umbrella EUAs for a product category. The umbrella EUA is issued with an appendix for any items submitted for the category, and Johnston noted that there are no specific submissions required for items in an umbrella EUA so long as the manufacturer can document that their product qualifies for that category and can deliver on the performance specifications spelled out by the agency.
Roughly 290 EUAs have gone out for diagnostics, and another 22 for personal protective equipment. Ventilators and other services have received 26 EUAs, while drugs and biologics are listed in another five. Johnston advised that the FDA requires that the submitter of an EUA filing use Form 3514 for some filings, a form that is typically used as a cover letter for 510(k) filings.
“Treat it like a typical premarket submission,” Johnston recommended, suggesting that sponsors ensure that an EUA submission is intelligible, well organized and concise. The EUA review times remain variable, Johnston said, but noted a sponsor’s EUA will lapse upon the expiration of the public health emergency. Any sponsor that intends to pursue a traditional premarketing authorization for a product currently operating strictly under the EUA program might want to be proactive about cobbling together a product dossier. Johnston said some manufacturers are filing their EUAs in parallel with the appropriate conventional premarket filing, and thus a quality management system (QMS) should be in place in order to minimize disruptions once the PHE ends.
Many ordinary regulatory requirements are waived for EUA products, such as the Quality Systems Regulation under Part 820, Part 806 mandates for reporting corrections and removals, and the regulations for unique device identifiers. Surgical gowns are still subject to Part 820, but Johnston recommended that companies without a Part 820-compliant QMS should stand one up as promptly as possible if they intend to continue to manufacture the regulated device. Even if the holder of the approval or authorization hires out the entirety of the manufacturing process to a contract manufacturer, that entity must have a QMS system in place in addition to the QMS for the contract manufacturer.
Viral transport media more tightly regulated
The FDA has attempted to self-regulate its own regulatory approaches to the pandemic, but one type of product is still subject to some fairly stringent requirements. For instance, the agency noted in an updated FAQ for viral transport media (VTM) for tests for the SARS-CoV-2 virus which indicates that VTM manufacturers must have a QMS that is in compliance with Part 820.
The agency offers four product codes for regulation of VTM, all of which are class I products except for the microbial nucleic acid storage and stabilization device under procode QBD. One of the regulatory stipulations is that manufacturers must validate the sterilization process for any VTM that is labeled as sterile, which includes validation of sterility for the duration of the product’s labeled shelf life.
The FDA said that while Part 820 is still technically in force for VTM, the agency will accept a QMS built around ISO 13485, the international standard that is the subject of a regulatory convergence policy at the agency. The FDA’s device center has had to punt on the rewrite of Part 820 to incorporate elements of ISO 13485 thanks to the pandemic, although the agency’s mantra for the past two years is that there is at least 95% overlap between the two standards. Manufacturers should provide documentation of compliance with the ISO standard with their EUA filings, the agency said.