The recommendations in this Guidance will remain in effect for the duration of the COVID-19 public health emergency and supersede the recommendations regarding decontamination which were previously included in FDA’s April 2020 guidance, Enforcement Policy for Face Masks and Respirators During the Coronavirus Disease (COVID-19) Public Health Emergency (Revised) (“Face Masks and Respirators Guidance”).
FDA’s recommendations included in this Guidance are based on the level or tier of decontamination or bioburden reduction intended for the proposed device based on the sponsor’s available data. This Guidance also communicates conservation strategies that are intended to augment specific controls and procedures developed by health care organizations such as the Centers for Disease Control and Prevention (“CDC”).
FDA recommends that sponsors of decontamination and bioburden reduction systems that utilize processes with well-controlled critical cycle parameters and process monitors such as biological indicators (“BI”), chemical indicators (“CI”), and parametric monitoring, and which follow the descending order of resistance of microorganisms to germicidal chemicals shown in Figure 1 below (“hierarchy”), provide bioburden reduction evidence in accordance to their respective decontamination or bioburden reduction tier(s).
Figure 1. Descending Order of Resistance of Microorganisms to Germicidal Chemicals 
Tier 1 - Decontamination of surgical masks and/or respirators for single- or multiple-users
Tier 1 systems are those intended for decontamination of surgical masks and/or respirators for either multiple-users or single users. For these systems, FDA recommends that sponsors demonstrate sporicidal or mycobatericidal decontamination with either a:
≥ 6-log spore reduction of the most resistant spore for the proposed process; or
≥ 6-log reduction of a Mycobacterium species (e.g., M. terrae or M. abscessus).
Due to the increased risk present in decontamination systems intended to decontaminate surgical masks and/or respirators for multiple-users, FDA expects that these systems demonstrate decontamination of the highest level of resistance in the hierarchy shown in Figure 1 above.
Tier 2 - Decontamination of surgical masks and/or respirators for single-users only
Tier 2 systems are those intended for decontamination of surgical masks and/or respirators used by the same person after decontamination (single-users). Because there is less risk of unintended transmission of SARS-CoV-2 or other pathogens while using these systems for single-users, FDA recommends that sponsors provide moderate level resistance data with respect to the hierarchy shown in Figure 1 above. The Agency specifically indicates that the sponsor should be able to demonstrate viral or vegetative bacterial decontamination with either a:
Tier 3 - Bioburden reduction of N95 respirators for single-users only to supplement existing CDC reuse recommendations
Tier 3 systems are those intended for bioburden reduction of N95 respirators for single-users to supplement existing CDC reuse recommendations under Crisis Capacity Strategies (during known shortages). FDA recommends that sponsors seeking an EUA under Tier 3 demonstrate viral or vegetative bacteria bioburden reduction with either a:
≥ 3-log reduction of a non-enveloped virus;
≥ 3-log reduction of two gram-positive and two gram-negative vegetative bacteria; or
other evidence demonstrating that the bioburden reduction system will reliably achieve a ≥ 3-log reduction in non-enveloped virus or vegetative bacteria, which could include published scientific literature and/or scientific and engineering studies.
In addition, FDA recommends that sponsors provide labeling that makes clear that the use of the bioburden reduction system is in addition to and does not replace CDC reuse recommendations.
For any decontamination or bioburden reduction system EUA issued, FDA will include appropriate conditions of authorization in addition to the mandatory conditions outlined in section 564(e)(1)(A) of the Federal Food, Drug, and Cosmetic Act. In addition to the recommendations FDA previously articulated in its Face Masks and Respirators Guidance, the Agency has recommended that the following information, among other things, be included in a pre-EUA and/or EUA application:
The proposed intended use of the decontamination or bioburden reduction system and a description of the technology.
A clear description of the process for decontamination or bioburden reduction controls including:
critical cycle parameters;
information on process monitors used to demonstrate the functionality of the cycle;
evidence supporting that the process is controlled and can reliably achieve and maintain critical cycle parameters; and
for energy-based methods requiring direct line-of-sight to the device surface, evidence supporting that there are process controls to prevent shadowing and allow line-of-sight access to all device surfaces.
Validation of decontamination or bioburden reduction, including:
demonstration of a robust ability to reliability decontaminate or reduce bioburden on compatible surgical masks and/or respirators which includes the appropriate level of validation as described above; and
evidence to demonstrate that soils are either removed or do not interfere with the decontamination or bioburden reduction processes.
Protocols and acceptance criteria for scale-up of the process.
User safety information regarding exposure to decontamination or bioburden reduction process residuals.
FDA recommends that systems intended for decontamination or bioburden reduction of compatible surgical masks and/or respirators are labeled in accordance with their respective intended use tier(s), as described below:
Tier 1 – Labeling of “Tier 1 systems” should include limitations of the system for the decontamination of compatible surgical masks and/or respirators that may be suitable for single- or multiple- users.
Tier 2 – Labeling of “Tier 2 systems” should include limitations of the system for the decontamination of compatible surgical masks and/or respirators that are only suitable for single-users.
Tier 3 – Labeling of “Tier 3 systems” should include limitations of the system for the bioburden reduction of compatible N95 respirators that are only suitable for single-users to supplement CDC reuse recommendations.
In addition, product labeling for compatible FDA-cleared or authorized surgical masks and/or respirators should clearly indicate whether the surgical masks and/or respirators are decontaminated (Tiers 1 and 2) or have undergone bioburden reduction (Tier 3). Labeling should also identify incompatible materials, how many times the surgical mask or respirator may be processed via decontamination or bioburden reduction, and advise users to discard surgical masks or respirators that are visibly damaged, soiled, or that fit poorly. For surgical masks or respirators that are decontaminated with a potential carcinogen, teratogen, or mutagen or chemicals known or suspected of having sensitizing effects, the sponsors should include appropriate warnings to alert users of potential health effects. Upon review of the labeling, FDA may identify additional labeling requirements as part of the system’s EUA conditions of authorization.
To summarize, FDA recommends that sponsors of decontamination or bioburden reduction systems include appropriate evidence to demonstrate decontamination or bioburden reduction of surgical masks and/or respirators based on the intended use tier and the hierarchy of resistance of the pathogens shown in Figure 1. Further sponsors should provide product labeling that is consistent with the respective tier to which their system is intended to perform.
Authored by Sandra Milena McCarthy and Seth Olson
 Modified from Favero, M.S. and Bond, W.W., Chemical Disinfection of Medical and Surgical Materials. In: Disinfection, Sterilization, and Preservation, 5th Ed Phila: Lippincott Williams & Wilkins 2001: 881-917