Emergency Use Authorization and Enforcement
FDA Response to COVID-19 – Personal Protective Equipment
In general, the FDA recommends that healthcare providers (HCPs) follow current CDC guidance regarding personal protective equipment (PPE) that should be used during the COVID-19 outbreak. FDA has published guidances for enforcement discretion during this time for a variety of PPE and provide information on the EUA application process regarding respirators. As will be discussed, the decontamination of single-use PPE devices has been authorized at this time as well. The released facemask and respirator guidance provides recommended information for EUA to reprocess certain disposable PPE. A face shield specific EUA has also been released.
On March 2, 2020 the FDA released its first EUA outside of diagnostic testing. The EUA authorized use of all disposable filtering facepiece respirators (FFR) approved by the National Institute of Occupational Safety and Health (NIOSH) as non-powered air-purifying particulate FFRs, including those that passed the manufacturers’ recommended shelf-life, for use in healthcare settings. The scope of authorization has been expanded and amended to clarify and include more PPE for use in a healthcare setting. Current authorization is provided in the reissued letter from March 28, 2020. Respirators included in the scope of authorization for use by HCPs in a healthcare setting are those included on the NIOSH Certified Equipment List (CEL) for non-powered air-purifying particulate FFRs and reusable respirators, and powered air purifying respirators (PAPRs). FFRs that were NIOSH-approved but have since passed the manufacturers’ recommended shelf-life, are not damaged, and have been held in accordance with manufacturers’ storage conditions in strategic stockpiles. Lastly, single-use NIOSH-approved FFRs that has been decontaminated pursuant to the terms and conditions of an authorized decontaminations system.
EUAs have since been published regarding imported Non-NIOSH-approved disposable FFRs and decontamination systems. A specific letter of authorization has also been published regarding disposable FFRs imported specifically from China.
Eligibility requirements for imported disposable FFRs to be distributed under these EUAs are consistent, with candidacy determined through marketing approval under certain regulatory jurisdictions or with evidence of performance-based compliance. Evidence of either may be submitted in the request for EUA to be assessed/verified by the FDA. Chinese manufacturers may be eligible if they hold one or more NIOSH approvals for other models of FFRs produced in accordance with the applicable standards of authorization in other countries that can be verified by the FDA.
Requirements differ between manufacturers, strategic stockpilers, and importers. Under the EUAs, the FDA has waived some good manufacturing practice requirements. Enforcement of quality system requirements (21 CFR 820) with respect to design, manufacture, packaging, labeling, storage, and distribution of authorized respirators is to be bypassed for products under these EUAs. Note that this waiver does not apply to any NIOSH requirements or requirements set forth by regulatory authorities outside the US.
In addition to the record retention previously mentioned, manufacturers and stockpilers are required to have records available for inspection by FDA upon request.
Specific conditions for EUA listing vary depending on actors, but certain conditions of interest are: disposable FFRs produced OUS must publish intended use and instructions for use on the manufacturer website and include a physical letter for each end user facility indicating manufacturer, model, intended use, and website; strategic stockpilers are authorized to distribute expired NIOSH-approved FFRs, but must alert and instruct recipients of the expired product to check the integrity of the respirator prior to use. Any expired FFRs that are damaged or in disrepair are not authorized for use under the EUA. Importers must notify manufacturers and the end users of the terms and conditions of the EUA.
For those manufacturers that do not fall under the eligibility conditions set forth by the EUAs, the FDA has opened an expeditious route to market in order to expand availability of surgical face masks (mask that covers user’s nose and mouth and provides a physical barrier to fluids and particulate materials, meeting certain fluid barrier protection standards) and respirators. For manufacturers with surgical face masks or respirators marketed OUS, FDA may be reached via email to assess a request, recommending general information of the product to be provided along with labeling, regulatory status, QMS compliance (21 CFR 820 or ISO 13485), and any standards compliance testing performed.
As mentioned previously, there has been a letter of authorization released for decontamination systems for the purpose of expanding availability of respirators through reprocessing and re-use of single-use devices. Five (5) decontamination EUAs have been released, each pertaining to a particular system: Battelle Decontamination System, STERIS Sterilization System, and Advanced Sterilization Products (ASP) STERRAD Sterilization System, Strykers’s STERIZONE VP4, and the Sterilucent Sterilization System. These authorizations allow for the decontamination of N95 respirators, and N95 equivalent respirators, that are not visibly soiled or contain cellulose-based material. All utilize vaporized hydrogen peroxide to achieve sterilization.
The STERIS, STERRAD, STERIZONE, and Sterilucent Systems are used within healthcare facilities for small-batch decontamination. The Battelle Decontamination System requires HCPs to package and ship contaminated respirators to their facility for processing, up to 10,000 per load; masks are returned to use sites. Each system requires its own EUA as each system is unique. However, for EUA request and issuance, the FDA has consistent requirements and conditions of release. For all system requests, FDA recommends including a description of the process controls, validation of the bioburden reduction/disinfection, description of the chain of custody and proper handling of decontaminated masks, material compatibility, performance and fit data after decontamination, and a copy of the decontaminated product labeling.
Further conditions include, but are not limited to, data collection pertaining to degradation of decontaminated respirators, and reporting of infection or potential infection of users of the decontaminated, compatible N95 respirators to the FDA.
Healthcare facilities are responsible for providing authorized labeling to HCPs who are or may be using the decontaminated compatible N95 respirators as well as inspecting decontaminated respirators before use for signs of degradation, and monitoring HCPs who use decontaminated respirators for signs and symptoms of potential infection with SARS-CoV-2 or other respiratory infections. Healthcare facilities are to report these potential infections to the manufacturer to be reported to the FDA.
Depending on the point of use, the tracked number of decontamination cycles that are within the use parameters are tracked by the healthcare facilities or the decontamination system provider. Small-batch sterilization processes for use within the healthcare facility require marking of decontamination cycles on masks by a user designated within the chain of command. Re-use number is specific for each device. With the Battelle system, healthcare facilities provide a collection station to consolidate contaminated masks to ship to the central decontamination location. Each facility provides a site identification on the outer shipping box to receive the same decontaminated respirators in return.
Face Shield EUA
The latest EUA release for PPE is regarding face shields as standalone devices. In a unique letter of authorization, the FDA has laid out conditions, that if met, require no interaction with the FDA for distribution of face shields for use by HCPs as PPE in healthcare settings in accordance with CDC recommendations to cover the front and sides of the face and provide a barrier of protection. Face shields authorized by the EUA may be effective at preventing exposure to certain particulates by providing minimal or low barrier protection to the wearer. Given that the materials are not flammable, or the product meets Class I or Class II requirements of 16 CFR 1610, and labeling contains identification of the body contacting materials, the standalone face shield fits within the scope of the EUA.
As with other PPE EUAs, certain quality system (21 CFR 820) requirements have been waived with respect to the authorized face shields under the EUA. Labeling requirements outside of the conditions of authorization have also been waived.
The conditions of authorization are listed in the letter of authorization and summarized here. Information to be provided in labeling includes body contacting material, intended us (single-use, single-user, multiple uses by the same user), and instructions for disinfection if applicable. This is to be distributed to each end user facility (in English) and may be provided with individual products. As with the other EUAs, adverse event reporting and record retention of associated products is to be conducted for the duration of the declared emergency and be made available upon request for inspection by FDA. Included in record retention is the requirement to track the number and location of distributed face shields by the manufacturer. Lastly, promotional material must be consistent with labeling and indicate that the product has not been FDA cleared or approved. The product has been authorized by FDA under an EUA for use by HCPs as PPE. No material should represent or suggest that the authorized face shields are safe or effective for the prevention or treatment of patients during the COVID-19 pandemic.
Face Mask EUA
A letter of authorization regarding face masks has been released by the FDA April 18, 2020. This letter is similar to that of face shields. Face masks that are used within the scope of the letter and comply with conditions and requirements of the letter, do not need to take any further action. Face masks are authorized under the EUA when they are intended for use by members of the general public, including HCPs in healthcare settings as PPE, to cover their noses and mouths, in accordance with CDC recommendations, to prevent the spread of SARS-CoV-2.
Labeling should reflect that it is a face mask, not a surgical mask, and is not intended for use as a surgical mask or to provide liquid barrier protection. The labeling should not suggest or represent that the face mask is intended for antimicrobial or antiviral protection or infection prevention. Face masks are not intended for particulate filtration. Labeling will include body contacting materials as well. Instructions for use and cleaning and/or disinfection (if applicable) will be made available to each end user or end user facility in hard copy or alternative (manufacturer website) form.
Previously listed requirements of EUAs apply regarding record retention, adverse event reporting, and distribution/inventory controls.
PPE Enforcement Discretion
Under the circumstances precluding the HHS declaration of emergency, the FDA is practicing enforcement discretion to expand availability of PPE for HCPs. Separate from the EUAs which are designated for specific devices and intended uses, this enforcement discretion is laid out for whole categories of medical devices on the market. FDA, again, recommends that HCPs follow current CDC guidance regarding PPE that should be used during the COVID-19 outbreak, and OSHA standards remain that apply to protect workers from infectious disease hazards.
Enforcement guidance documents have been released for PPE, specifically face masks, respirators, gowns, apparel, and gloves. During this time, the FDA “does not intend to object” to the distribution of products without compliance to certain regulatory requirements. For listed PPE, requirements for registration and listing (21 CFR 807), quality system regulation (21 CFR 820), reports or corrections and removals (21 CFR 806), and unique device identification (21 CFR 830, 21 CFR 801.20). This non-objective stance to distribution of products under the emergency are held upon certain conditions listed in each guidance. All products must maintain accurate labeling identifying the product, any body contacting materials, and recommendations that would reduce the risk of use. This includes labeling contraindications such as antimicrobial or antiviral protection or uses for infection prevention or reduction. An example of device specific labeling considerations is no indication for use of gloves with chemotherapy drugs, fentanyl and other opioids, or dermatitis prevention. Non-labeling considerations include compliance with flammability and liquid barrier protection standards for gowns and surgical masks.
Waiver of the regulatory requirements apply only for the duration of the COVID-19 emergency and in accordance with device specific conditions for distribution.