The U.S. FDA held a July 7 webinar to go over a recent guidance on decontamination and bioburden reduction of N95 masks for the COVID-19 pandemic, and one of the take-away messages is that the agency is still quite concerned about the impact of residues left over from those processes, given that some of these residues can be inhaled by the wearer and trigger health problems of their own.

The webinar was predicated on a need to provide more detail on the recent guidance for emergency use authorization (EUA) for processing of surgical masks and respirators for the COVID-19 pandemic, the scope of which includes both bioburden reduction and decontamination. The immediately-in-effect (IIE) guidance covers submissions both prior to an EUA filing and an EUA submission, although the guidance will expire as soon as the declaration of public emergency expires.

No good answers to concerns regarding user markings

One of the issues that arose during the question-and-answer portion of the webinar was in connection with the effect of isopropyl alcohol on N95 mask markings, given that this decontaminant can blot out the markings that are used to ensure the same user will receive a decontaminated mask. Binita Ashser, director of the office of surgical and infection control devices at the FDA’s Center for Devices and Radiological Health, said there are few good alternatives to ensuring permanent pen markings aren’t damaged, given that tabs can be lost and markings on mask straps might interfere with a strap’s elastic properties. “It is a challenge, and we completely acknowledge that,” Asher said.

Asher said also that residuals from a decontamination/bioburden reduction process are an important consideration, but that the lack of experience with some of these agents leaves the agency with little in the way of ready advice as to how to eliminate residuals.

The FDA is working with the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration on these questions. This question has received “a significant amount of scrutiny” from all three agencies, Asher said. The International Standards Organization has several standards that may be of interest, including ISO 10993-7, which deals with ethylene oxide residuals on medical device sterilization.

The ISO standard is limited to devices that come into direct contact with the patient, but OSHA was said to have nothing to add regarding removal of residuals for many of the available sterilants and antibiotic treatments. OSHA is handling such requests for information on a case-by-case basis, and the FDA is in essentially the same predicament in some instances, given the paucity of data regarding the use of some of these cleaning agents on the materials found in N95 masks and other implements used in health care settings.

Guidance lists three tiers of pathogen removal

The FDA’s view is that bacterial spores are perhaps the most resistant of a number of pathogens to decontamination and bioburden reduction, at least compared to mycobacteria non-lipid or small viruses. Lipid and medium-sized viruses are more susceptible, a set of characteristics that informed a framework for the agency’s recommendations. The guidance said that tier 3 processing for surgical masks and respirators must demonstrate at least a six-log reduction for the most resistant spore for the proposed process in the context of items that will be used for single-users and multiple users. Alternatively, a sponsor can demonstrate a minimum six-log reduction of either of two mycobacterium species (M. terrae and M. abscesses).

For decontamination/bioburden reduction methods applied toward a single-user article (tier 2), sponsors should demonstrate at least a six-log reduction of three non-enveloped viruses or at least a six-log reduction of two gram-positive and two gram-negative vegetative bacteria.

Tier 3 requirements, the least stringent of the three, are applied to single-user N95 respirators as a supplement to existing reuse recommendations posted by the CDC. This approach calls for a three-log reduction of non-enveloped viruses, a three-log reduction of two gram-positive and two gram-negative viruses, or “other evidence demonstrating similar effect.”

Elizabeth Claverie-Williams, assistant director for disinfection and reprocessing at the FDA’s Center for Devices and Radiological Health, said on the webinar that all EUA requests must provide evidence of a repeatable achievement of an endpoint. Depending on the endpoint, the evidence may include microbial testing by the sponsor, while the literature on these processes can be used to aid in the sponsor’s demonstration of the effectiveness of the process in question as well.

The sponsor of an EUA must offer evidence that the process has not affected the ability of the respirator to fend off pathogens, and respirators will have to demonstrate filtration capacity after the maximum number of treatment cycles. Sponsors should remain mindful that masks containing cellulose are not compatible with some chemicals, such as hydrogen peroxide. Labeling and engineering and process controls should be included to help reduce the risk of mask failure, Claverie-Williams said.

No Comments