key: cord-0839082-u9uuuu38
authors: Rodriguez-Martinez, Carlos E.; Sossa-Briceño, Monica P.; Cortés-Luna, Jorge A.
title: Decontamination and reuse of N95 filtering facemask respirators: a systematic review of the literature
date: 2020-07-08
journal: Am J Infect Control
DOI: 10.1016/j.ajic.2020.07.004
sha: eef03830aed7aa44e00dede0f480b528e51f2323
doc_id: 839082
cord_uid: u9uuuu38

INTRODUCTION: As has happened in other emerging respiratory pandemics, demand for N95 filtering facemask respirators (FFRs) has far exceeded their manufacturing production and availability in the context of the SARS-CoV-2 pandemic. One of the proposed strategies for mitigating the massive demand for N95 FFRs is their reuse after a process of decontamination that allows the inactivation of any potentially infectious material on their surfaces. This article aims to summarize all of the available evidence on the different decontamination methods that might allow disposable N95 FFRs to be reused, with emphasis on decontamination from SARS-CoV-2. METHODS: We performed a systematic review of the literature in order to identify studies reporting outcomes of at least one decontamination method for inactivating or removing any potentially infectious material from the surface of N95 FFRs, specifically addressing issues related to reduction of the microbial threat (including SARS-CoV-2 when available), maintaining the function of N95 FFRs and a lack of residual toxicity. RESULTS: We identified a total of 14 studies reporting on the different decontamination methods that might allow disposable N95 FFRs to be reused, including small-scale energetic methods and disinfecting solutions/spray/wipes. Among these decontamination methods, ultraviolet germicidal irradiation (UVGI) and vaporized hydrogen peroxide (VHP) seem to be the most promising decontamination methods for N95 FFRs, based on their biocidal efficacy, filtration performance, fitting characteristics, and residual chemical toxicity, as well as other practical aspects such as the equipment required for their implementation and the maximum number of decontamination cycles. CONCLUSIONS: Although all the methods for the decontamination and reuse of N95 FFRs have advantages and disadvantages, UVGI and VHP seem to be the most promising methods.

An outbreak starting in December 2019 caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, has posed a severe threat to public health and local economies around the globe. 1 As the pandemic accelerates, the increased risk of infection of health-care workers due to a rise in their demand makes their safety, including an adequate provision of personal protective equipment (PPE), a cause of great concern. 2 Recent guidelines proposed by the Infectious Diseases Society of America (IDSA) recommend the use of a reprocessed N95 respirator for reuse during respirator shortage based on laboratory evidence, due to lack of clinical experience with the decontamination process. 3 Among the various PPEs, disposable N95 filtering facemask respirators (FFRs) are of critical importance for confronting the SARS-CoV-2 pandemic because of their tight fit and their filtration capability of at least 95% of airborne particles, including large and small particles. 4 However, as has happened in other emerging respiratory pandemics, demand for N95 FFRs has far exceeded their manufacturing production and availability. This is, among other factors, due to the minimum number of N95 FFRs required for each health-care worker involved in direct patient contact, assuming adequate care is taken. For a recent respiratory pandemic outbreak of influenza, there were estimations of requirements of as many as 360 million FFRs, in scenarios assuming a pandemic duration of 24 weeks. 5 Ideally, disposable N95 FFRs should be discarded after each patient encounter and after aerosol-generating procedures (considering that they are potentially fomites because they remove pathogenic microorganisms from aerosols generated by infected individuals), when they become damaged or deformed, when they no longer form an effective seal to the face, when they become wet or visibly dirty, when breathing becomes difficult, as well as when they become contaminated with blood, respiratory or nasal secretions, or other bodily fluids. 6 Some of these recommendations are supported by evidence showing the probability of viral contamination and the viability of respiratory viruses on N95 FFRs and other inanimate surfaces for variable periods, the ability of the influenza virus to persist for 6 days on the outer side of the N95 FFRs having been demonstrated. 7, 8 Specifically for SARS-CoV-2, although it is more stable on plastic and stainless steel than on copper and cardboard, viable virus can be detected for up to 72 hours. 9 One of the proposed strategies for mitigating the massive demand for N95 FFRs not met by manufacturing supply that typically occurs during a respiratory pandemic that helps to ensure their continued availability in healthcare environments is their reuse after a process of decontamination that allows the inactivation of any potentially infectious material on their surfaces. 10 Although various decontamination methods have been used, there are concerns over certain characteristics of the N95 FFRs with respect to their utilization, such as alterations in their physical appearance/odor, structural integrity, filtration efficiency, fit and seal and filter airflow resistance, degradation of their material, and chemical residues that are potentially toxic or irritate the skin (due to the chemical disinfectants required for rinsing and drying). The requirement for specialized equipment for using the decontamination methods must also be considered, as well as their speed and ease of use, cost, and the maximum allowed number of decontamination cycles. 6 However, to the best of our knowledge, no systematic review has summarized the findings of studies that have assessed the above-mentioned advantages and disadvantages of all available decontamination methods for N95 FFRs.

The present article aims to summarize all of the available evidence on the different decontamination methods that might allow disposable N95 FFRs to be reused, with emphasis on decontamination from SARS-CoV-2.

Potentially relevant studies were identified thorough a search of the literature in the electronic databases MEDLINE, EMBASE, CINAHL, and SCOPUS up to July, 2020, using the terms ("Decontamination"(Mesh) OR "Equipment Reuse"(Mesh) OR "Microbial Viability"(Mesh) OR "Virus Inactivation"(Mesh) OR "Disinfection"(Mesh) OR "Respiratory Tract Infections/prevention and control"(Mesh)) AND ("Respiratory Protective Devices"(Mesh) OR "N95 respirator" OR "filtering facepiece respirator"). Two review authors (CRM, MPS) scanned the abstracts and titles of articles retrieved by the electronic databases according to the eligibility criteria, retrieving full copies of all those deemed potentially eligible for closer examination. Disagreement was resolved by consensus. The electronic database searches were supplemented by information obtained from the references of the identified studies. We included citations in any language.

To be included, the studies had to meet the following criteria: studies reporting outcomes of at least one decontamination method for inactivating or removing any potentially infectious material from the surface of N95 FFRs, including filtration performance, structural integrity, and potentially toxic or chemical residues postdecontamination. Studies that reported on the efficacy of decontamination methods on elastomeric respirators were excluded. Likewise, studies in which it was not possible to extract outcomes of interest separately for the different decontamination methods, or studies published solely in abstract form, were not eligible for inclusion in the review.

Two reviewers (CERM and JACL) independently used a data extraction sheet designed a priori to obtain the specific data required for this review. From the included studies, we extracted descriptive data (first author, year), type of decontamination method(s) used, and details of their implementation, such as the equipment required, speed and ease of use, cost, and the maximum allowed number of decontamination cycles. Likewise, we extracted data on outcomes of relevance, including alterations in the physical appearance/odor, structural integrity, filtration efficiency, fit and seal, and filter airflow resistance of the N95 FFRs, as well as chemical residues that are potentially toxic or that irritate the skin upon use. Figure 1 shows the selection process of the studies. The systematic search of databases retrieved 244 studies. Among those, we excluded 237 studies. The most common reason for excluding studies was that they did not meet the eligibility criteria.

Eight additional studies that met the inclusion criteria were identified from the references of eligible articles. In the end, a total of 15 studies reporting on the different decontamination methods that might allow disposable N95 FFRs to be reused were included in the review and presented by type of decontamination method. Upland, CA, USA), the lamp's UV-C wavelength irradiance ranged between 1.6 mW cm 2 and 2.2 mW cm 2 . Virus-laden respirators were placed inside the cabinet directly under the ultraviolet lamp, with the convex panel facing the treatment, and were exposed for a total of 15 min at a UV-C wavelength dose of 18 kJ m 2 . After the decontamination procedure, the reduction in viral recovery (expressed as log10 TCID50/mL reduction) was ≥4.54 and ≥4.65 for the FFRs models, respectively, and no viable virus was detectable, with the number of amplification cycles to detect vRNA of 2.97 and 5.60 for the FFRs models, respectively. Additionally, the post-decontamination filter performance analyses showed that the mean penetration of 1% NaCl aerosol at 300 nm particle size was 0.99 and 0.37 for the FFR models, respectively. 12 Viscusi et al. placed N95 FFRs on the working surface of a Sterilgard III laminar flow cabinet (The Baker Company, Sanford, ME, USA) fitted with a 40-WUV-C light (average UV intensity experimentally measured to range from 0.18 to 0.20 mW cm 2 ), fifteenminute exposure to each side (outer and inner), 176-181 mJ cm-2 exposure to each side of the FFR, for a total time of 30 minutes. All laboratory experiments were conducted under standard laboratory conditions (21 ± 2 °C and relative humidity of 50%-10%) on triplicate sets of FFRs. Ultraviolet germicidal irradiation treatment did not affect the filter aerosol penetration (pre-and post-decontamination average percentage of sodium chloride penetration of the three surgical N95 FFRs evaluated: 1.57 ± 0.83 vs. 1.86 ± 0.97, 0.335 ± 0.19 vs. 0.371 ± 0.21, and 0.716 ± 0.37 vs. 0.720 ± 0.37) or physical appearance of the FFRs. There were statistically significant, although not clinically significant, differences between pre-and post-decontamination measures of filter airflow resistance in two of the three surgical N95 FFRs evaluated (pre-and postaverage decontamination resistance in mmH 2 O: 8.4 ± 0.50 vs. 9.2 ± 0.44, 6.1 ± 0.15 vs.

7.1 ± 0.61, and 6.7 ± 0.17 vs. 6.6 ± 0.26). No known health risks to the user were identified. 13 In addition to these results, Viscusi et al. also showed that N95 FFR users would be unlikely to experience a clinically meaningful reduction in fit, increase in odor, increase in discomfort, or increase in difficulty in donning after UVGI decontamination. 14 Lindsley et al. exposed both sides of material coupons and respirator straps from four models of N95 FFRs to UVGI doses from 120 to 950 J/cm 2 and evaluated the particle penetration, flow resistance, bursting strengths of the individual respirator coupon layers, and breaking strength of the respirator straps. N95 FFRs were exposed to ultraviolet light with a primary wavelength of 254 nm (UV-C) in a custom-made 91 cm × 31 cm × 64 cm high chamber. The chamber was fitted with two 15-watt T-150 254 nm UV-C lamps in a reflective housing and lined with black felt to minimize reflections. UV-C irradiance was measured using a radiometer (ILT-1700, International Light Technologies, Peabody, MA). UVGI exposure led to only a small increase in particle penetration (up to 1.25%) and had little effect on the flow resistance. UVGI exposure had a more pronounced effect on the strengths of the respirator materials. At the higher UVGI doses, the strength of the layers of respirator material was substantially reduced (in some cases, by >90%). The changes in the strengths of the respirator materials varied considerably among the different models of respirators. UVGI had less of an effect on the respirator straps; a dose of 2360J/cm 2 reduced the breaking strength of the straps by 20%-51%. 15 Bergman et al. evaluated changes in physical appearance, odor, and laboratory performance (filter aerosol penetration and filter airflow resistance) of six N95 FFRs models after three cycles of decontamination with UVGI. The determined by a 50% tissue culture infectious dose (TCID50/mL) assay. Significant reductions (≥3 log) in influenza viability for both soiling conditions were observed on facepieces from 12 of 15 FFR models (with a mean log reduction ranging from 1.42 to 4.84 log TCID50/mL for mucin-soiled facepieces, and from 1.25 to 4.64 log TCID50/mL for sebum-soiled facepieces) and straps from 7 of the 15 FFR models (with a mean log reduction ranging from 0.00 to 4.31 log TCID50/mL for mucin-soiled straps, and from 0.08 to 4.40 log TCID50/mL for sebum-soiled straps). 17 Heimbuch et al. evaluated the decontaminant efficacy and the durability and functionality of fifteen N95 FFR models after multiple cycles of UVGI. Using a Mineralight® XX-20S 20-W UV bench lamp, four UV doses were evaluated: 1 × 103, 5 × 105, 1 × 106, and 2 × 106 µJ/cm2. For each test, FFRs were inoculated in a Class II biological safety cabinet (BSC) with ten 1-µL droplets of ~109 TCID50/mL H1N1 influenza onto each of the four surfaces selected for inoculation. After the droplets had dried, a soiling agent (synthetic skin oil or artificial saliva buffer) was applied over each inoculated surface to act as a protective factor. The test results were reported as the reduction of the virus titer due to treatment with UV, expressed as log10. The TCID50/mL was determined using the Spearman-Karber method. UVGI performance varied considerably for all 15 FFR models tested, with log reductions ranging from 0.00 to 4.85 log10 TCID50/mL, based on inoculation location, soiling agent, and control recovery. For all three soiling conditions, a direct relationship was demonstrated between UV dosage and influenza decontamination, with no viable virus detected after UV treatment ≥1 J/cm 2 . Additionally, it was demonstrated that up to 20 cycles of UVGI treatment (approximately 1 J/cm2 per cycle) do not exert a meaningfully significant effect on fit, airflow resistance, or particle penetration for the 15 FFR models tested.

Strap tension data indicated that 10 UVGI cycles do not have a significant effect on FFR straps, but 20 UVGI cycles may have a significant effect on straps from some N95 FFR models (3M 1860, 3M 1870, and Kimberly-Clark PFR models). 10 Lin et al. determined the relative survival of Bacillus subtilis spores loaded onto N95 FFRs after UVGI (UVA 365 nm, UVC 254 nm) decontamination under a worst-case temperature (37 °C, similar to body temperature) and humidity (95% relative humidity, the maximum feasible relative humidity value) that prevails when an FFR is placed in a zipper bag in a healthcare worker's pocket. The treatment proceeded as follows: an N95 FFR was placed 10 cm below a 6 W handheld UV lamp (model UVGL-58, VUP LLC, Upland, CA) that emitted a wavelength of 254 nm (UVC, 18.9 mW/cm 2 ) or 365 nm (UVA, 31. 2 mW/cm 2 ). Both sides of each N95 FFR were exposed for different lengths of time: 1, 2, 5, 10, and 20 minutes, in a BSC. The UV intensity was measured using a handheld laser power and energy meter (OPHIR NOVA II, model Nova II PD300-UV) and was reported as a mean of five measurements over a 10 × 10 mm aperture with a swivel mount and a removable filter. Colony-forming units (CFUs) were counted, and their relative survival (RS) was calculated. Without decontamination, 59 ±8% of the loaded spores survived for 24 hours. No colony was recovered after exposure to UV-C for as little as 5 minutes. However, RS remained above 20% after 20 minutes of irradiation by UV-A, exponentially decaying with increased exposure time. 18 Fischer et al. analyzed the ability of UV radiation to inactivate SARS-CoV-2 on N95 FFRs (50 µl of 10 5 TCID50/mL of SARS-CoV was applied on N95 and stainless steel) and used quantitative fit testings to measure their filtration performance after each decontamination run and 2 hours of wear, for three consecutive decontamination and wear sessions. Plates with fabric and steel discs were placed under an LED high-power UV germicidal lamp (effective UV wavelength 260-285 nm) without the titanium mesh plate (LEDi2, Houston, Tx) 50 cm from the UV source. At 50 cm, the UVAB power was measured at 5 µW/cm2 using a General UVAB digital light meter (General Tools and Instruments New York, NY). The plates were removed at 10, 30, and 60 minutes, and 1 mL of cell culture medium added. N95 FFRs integrity was quantitatively determined using the fit factor, a measure of filtration performance: the ratio of the concentration of particles outside the mask to the concentration inside, requiring a minimum fit factor of 100 for a mask to pass a fit test. UV inactivated SARS-CoV-2 rapidly from steel (decay rates of viable virus titers over time and half-lives; median, interquartile range: 0.733, 0.649-0.802 min), but more slowly on N95 fabric (decay rates of viable virus titers over time and half-lives; median, interquartile range: 6.26, 5.31-7.15 min). The UV-treated masks retained filtration performance comparable to the control group after two cycles of decontamination and maintained acceptable performance after three cycles. 19 Liao et al. process but differing in some aspects (e.g. gas concentration, chamber volume, and duration). Respirators tested using these treatments were shipped to and from a commercial facility specializing in low-temperature sterilization methods. Four FFR samples were placed in standard poly/paper pouches and treated with EtO. All respirator samples were exposed to EtO for one hour, followed by a four-hour aeration interval. The respirators were shipped back to the investigators and subsequently tested in house for filtration efficiency within 72 hours of receipt. After EtO decontamination, the average penetration slightly increased for N95 FFRs, though not beyond their respective certification criteria (mean and standard deviation % penetration: 0.7 ± 0.267 vs. 0.729 ± 0.136 vs. 0.35 ± 0.019, for as-received, EtO 3M 5XL, and EtO 3M 4XL postdecontamination, respectively). EtO 3M 5XL was found to be slightly less degraded than EtO 3M 4XL. 11 Viscusi et al. differing only in duration and capacity. Respirators tested using these treatments were shipped to and from a commercial facility specializing in low-temperature sterilization methods and were tested in-house for filtration efficiency within 72 hours of receipt from the commercial facility. The STERRAD® sterilization process is less effective when used on cellulose-based products; hence the use of Tyvek/Mylar pouches was required.

Since there were no inherent hazardous residues as a result of the STERRAD® process, no aeration interval was necessary. Aluminum nosebands were slightly tarnished and visibly not as shiny when compared with their as-received counterparts after both STERRAD® treatments. For both treatments, the average penetration of the 95 FFR model did not significantly increase and remained below certification limits.

STERRAD® NX was found to be slightly less degraded than STERRAD® 100S, but the difference was not statistically significant (mean and standard deviation % penetration: FFRs after bleach decontamination. The treatment proceeded as follows: a 0.4 mL volume of bleach with various concentrations (5.4% (w/w) as Cl2: original; 2.7%: one part bleach to one part of deionized water; 0.54%: one part bleach to nine parts of deionized water) was added to the center of the surface of the N95 FFR using a pipette, the FFR was then dried in a petri dish in a BSC for 10 minutes, the CFUs were counted, and their (RS) was calculated. Without decontamination, 59 ±8% of the loaded spores survived for 24 hours. In the bleach decontamination test, no colony was recovered after 5.4%, 2.7% or 0.54% sodium hypochlorite was used, constituting no dilution, twofold, and 10-fold dilution, respectively. 18 Bergman et al. evaluated changes in the physical appearance, odor, and laboratory performance of six N95 FFR models after three cycles of decontamination with bleach.

The experimental conditions and parameters were as follows: 30-min submersion in 0.6% (one part bleach to nine parts of deionized water) solution of sodium hypochlorite (original concentration = 6% available as Cl2). Manufacturing specification: 6.00 ±0.06% Bleach decontamination caused various effects: for all FFR models, metallic nosebands were slightly tarnished and visibly not as shiny when compared with their as-received counterparts. For those models with staples, the staples were oxidized to varying degrees. Some models had dissolution of nose pads, and discoloration (yellowing) of inner nose pads, material adjacent to nose pad, and other areas of the FFRs (bleeding of printed ink lettering). Additionally, following air-drying between exposure cycles (at least 16 hrs), all FFRs that were exposed to bleach were dry to the touch, and all still had a characteristic bleach odor. 16 Liao et al. sprayed three models of N95 FFRs with approximately 0.3−0.5 mL of household chlorine-based disinfectant (∼2% NaClO). Samples were left to air-dry and off-gas completely, while hanging. From the first disinfection, ethanol drastically degraded the filtration efficiency (73.11% ± 7.32), while the pressure drop remained comparable (9.0Pa ± 1.0). 20 in an oven (Thermo Fisher Scientific Inc., Marietta, OH, USA), and heated to 65 ± 5 °C for 3 h. This allowed the liquid to reach the desired temperature before any decontamination tests. For testing, the container was removed from the oven, and a single virus-contaminated respirator was placed on the rack. For each decontamination procedure, the container was opened and the FFR placed onto the rack with the convex surface pointed toward the water layer. The container was then sealed and returned to the oven for the 20-min treatment. After the decontamination procedure, the reduction in viral recovery (expressed as log10 TCID50/mL reduction) was ≥4.62 and ≥4.65 for the FFR models, respectively, and no viable virus was detectable, with several amplification cycles to detect vRNA of 5.62 and 42.45 for the FFR models, respectively. Additionally, the post-decontamination filter performance analyses showed that the mean penetration of 1% NaCl aerosol at 300-nm particle size was 1.04 and 0.99 for the FFR models, respectively. 12 Fischer et al. analyzed the ability of heat to inactivate SARS-CoV-2 on N95 FFRs (50 µl of 105 TCID50/mL of SARS-CoV was applied on N95 and stainless steel) and used quantitative fit testings to measure their filtration performance after each decontamination run and 2 hours of wear, for three consecutive decontamination and wear sessions. Plates with fabric and steel discs were placed in a 70 °C oven. Plates were removed at 10, 20, 30, and 60 minutes, and 1 mL of cell culture medium added.

The N95 FFRs' integrity was quantitatively determined using the fit factor, a measure of filtration performance: the ratio of the concentration of particles outside the mask to the concentration inside, requiring a minimum fit factor of 100 for a mask to pass a fit test. CFUs were counted, and their RS was calculated. Without decontamination, 59 ±8% of the loaded spores survived for 24 hours. Just after spiking with ethanol, the RS was found to have declined from 100% to 68%-75%. When 0.4 mL of 70% ethanol was applied, the RS fell to 22% in 24 hours. The RS fell to 20% when 80% ethanol was used. 18 Fischer et al. analyzed the ability of 70% ethanol to inactivate SARS-CoV-2 on N95 FFRs (50 µl of 105 TCID50/mL of SARS CoV-2 was applied on N95 and stainless steel) and used quantitative fit testings to measure their filtration performance after each decontamination run and 2 hours of wear, for three consecutive decontamination and wear sessions. Fabric and steel discs were placed into the wells of one 24-well plate per time-point and sprayed with 70% ethanol to saturation. The plate was tipped to near vertical, and five passes of ethanol were sprayed onto the discs from approximately 10 cm. After 10 minutes, 1 mL of cell culture medium was added. The N95 FFRs' integrity was quantitatively determined using the fit factor, a measure of filtration performance: the ratio of the concentration of particles outside the mask to the concentration inside, requiring a minimal fit factor of 100 for a mask to pass a fit test. Ethanol yielded extremely rapid inactivation both on N95 (decay rates of viable virus titers over time and half-lives; median, interquartile range: 0.639, 0.55-0.721 min) and on stainless steel (decay rates of viable virus titers over time and half-lives; median, interquartile range:

1.06, 0.888-1.23 min). Quantitative fit tests showed that the filtration performance of the N95 FFRs was not markedly reduced after a single decontamination with 70% ethanol.

However, subsequent rounds of decontamination caused sharp drops in the filtration performance of the ethanol-treated masks. 19 Liao et al. immersed three models of N95 FFRs into a solution of 75% ethanol and left them to air-dry (hanging), and they were subsequently tested. At the first disinfection, ethanol drastically degraded the filtration efficiency (56.33% ± 3.03), while the pressure drop remained comparable (7.7Pa ± 0.6). 20 

Heimbuch et al. evaluated the ability of commercially available wipe products to clean three models of surgical N95 FFRs contaminated with aerosols of mucin or viable Staphylococcus aureus. After cleaning, FFRs were separated into components (nose pad, fabrics, and perforated strip), and contaminants were extracted and quantified.

Filtration performance was assessed for cleaned FFRs. Wipe products selected for this study were 504/07065 respirator cleaning wipes (3M Company, StPaul, MN),15, which contain benzalkonium chloride (BAC); Hype-Wipes (Current Technologies, Inc, Crawfordsville, IN),16, which contain 0.9% hypochlorite (OCL); and Pampers wipes (Proctor &Gamble, Cincinnati, OH),17, which contain no active antimicrobial ingredients (i.e., inert). S. aureus was applied to both interior and exterior FFR surfaces (in separate experiments) to provide sufficient sensitivity for reliable analysis. Mucin was applied as a heavy loading (1 mg/cm2) only to exterior surfaces. After cleaning, the FFRs were incubated for 15 minutes at room temperature before quantification of contaminants.

The filters' performance was evaluated after three cleaning cycles using a model 8130 automated filter tester (TSI Inc, Shore-view, MN). While no mucin was detected in replicates using the OCL wipes, the mean removal efficiency of mucin by BAC and inert wipes ranged from 21.47% to 76.41%. Otherwise, the mean removal efficiency of Staphylococcus aureus by OCL wipes ranged from 98.98 to >99.99%, the mean removal efficiency of S. aureus by BAC wipes ranged from 68.92 to >99.99%, and the mean removal efficiency of S. aureus by inert wipes ranged from 59.37 to >96.53%.

Removal was less effective from nose pads and perforated edges. Although particle penetration following cleaning yielded mean values <5%, BAC wipes caused more penetration than the other wipes, this difference being significant for two models of FFRs. 24 

Viscusi et al. evaluated the filtration performance of an N95 FFR after tap water, using a poly-dispersed sodium chloride aerosol test method. This treatment involved submerging the test respirators in tap water for 30 minutes and was included as a control to reveal any effect due to immersion in tap water and air drying. No significant visible changes were detected. As expected, the average filter penetration was unchanged for N95 FFRs (mean and standard deviation % penetration: 0.7 ±0.267 and 0.72 ± 0.202, for as-received and tap water post-decontamination, respectively). 11

Viscusi et al. evaluated the filtration performance of an N95 FFR after soap and water at two different time intervals, using a poly-dispersed sodium chloride aerosol test method. 

This systematic review summarized all the existing evidence on the different decontamination methods that might allow disposable N95 FFRs to be reused, specifically addressing issues related to biocidal efficacy, filtration performance, fitting characteristics, and residual chemical toxicity, as well as other practical aspects such as the equipment required for their implementation and the maximum number of decontamination cycles. Our findings show that the issues mentioned above largely depend not only on the decontamination method itself, but also on other factors, such as the N95 FFR model, the presence of soiling agents, the surface type, the directness of exposure to the target surface for decontamination, the type of nucleic acid of the virus, the water-vapor content on the surface, and specific characteristics of each decontamination method, such as dose, intensity, concentration, and time of exposure.

Our review shows that although not all methods have been evaluated for their efficacy in virus inactivation, UVGI, VHP, heat, and ethanol are specifically efficacious against SARS-CoV-2. Our review supports the recent recommendations made by the IDSA related to the use of reprocessed N95 for reuse during a contingency 3 and provides wider support for alternative methods. It must also be recognized that clinical evidence for the reuse of decontaminated N95 is lacking, and such a study would be of interest in crisis-capacity settings but also relevant for less-developed countries.

Although all the methods have advantages and disadvantages (Table 1) , UVGI and VHP seem to be the most promising decontamination methods for N95 FFRs. UVGI decontamination has many benefits: it is the most frequently studied and reported decontamination method for N95 FFRs that has demonstrated significant reductions in influenza virus recovery and viability even with soiling conditions (mucin and sebumsoiled facepieces), 17 All these biocidal effects have been demonstrated without known health risks to the users nor a meaningfully significant effect on filter aerosol penetration, filter airflow resistance, [11] [12] [13] 15 fit and seal, odor (although a singed smell has been reported on FFRs following UVGI treatment, this does not necessarily indicate toxicity, and it generally dissipates naturally within 4 hours), 25 discomfort, difficulty in donning, or physical appearance 14 after up to 20 of cycles of decontamination. 10 Additionally, UVGI is the most viable treatment for large-scale applications, due to its simplicity of use and its ability to rapidly scale up the process by adding inexpensive FFR UVGI exposure units.

UVGI technology has also been developed for whole-room decontamination for hospitals, which provides opportunities for dual-use technologies and reduction of implementation costs. 13 However, several aspects need to be taken into account before being truly optimistic: UVGI decontamination is based on supplying an adequate dose to the contaminated area. 26 The UVGI dose required for decontamination, which is microbe specific (e.g., a direct relationship between UV dosage and influenza decontamination has been demonstrated, with no viable virus detected after UV treatment ≥1 J/cm 2 10 ), is a function of irradiance and time. 26 However, at the higher UVGI doses, there are greater reductions in the strength of the layers of FFR material. 15 Furthermore, UVGI efficiency is hampered by shadowing produced by the multiple layers of the N95 FFRs. 17 An additional factor to consider is that UVGI performance can vary among different models of N95 FFRs, different parts of the respirators, distinct types of UVGI, and number of cycles of decontamination. Although 10 UVGI cycles do not have a significant effect on FFR straps, 20 cycles may have a considerable impact on the strap tension of some N95 FFR models (3M 1860, 3M 1870, and Kimberly-Clark PFR models). 10 While no colony of B. subtilis was recovered after 5 minutes of exposure to UV-C, RS remained above 20% after 20 minutes of irradiation by UV-A. 18 Moreover, UVGI has been demonstrated to inactivate SARS-CoV-2 rapidly on steel but more slowly on N95 fabric, likely due to its porous nature. 19 Finally, UVGI decontamination is limited by the available working surface area of a biosafety cabinet equipped with a UV-C source or other area being irradiated by a UVGI source. 13 VHP is another widely-studied decontamination method for N95 FFRs that has been shown to have several advantages: complete inactivation of G. stearothermophilus spores following 50 repeat aerosol inoculation/decontamination cycles, 21 complete eradication after a single VHP cycle of 3 aerosolized bacteriophages (T1, T7, and

Pseudomonas phage phi-6), which are a reasonable proxy for SARS-CoV-2, 22 and extremely rapid inactivation of SARS-CoV-2 both on N95 and on stainless steel. 19 All these biocidal effects have been demonstrated without meaningfully significant effects on filtration performance, filter aerosol penetration, fit, and filter airflow resistance after up to 50 cycles of decontamination. 21 Additionally, there are no vapors potentially toxic to humans nor environmentally hazardous residues as a result of the VHP decontamination process. 11 However, after VHP decontamination, some studies have reported a fragmentation of the elastic material in the straps when stretched (after 30 HPV, but not after 10 or 20 HPV cycles) 21 and a slight tarnishing of the metallic nosebands. 13 A potential disadvantage is that although the total VHP cycle time is short compared to other decontamination methods, the throughput capability of VHP processing is limited by the fact that cellulose-based products (e.g., cotton, which may be present in some head straps or some FFR layers) absorb hydrogen peroxide and can cause the STERRAD® cycle to abort due to low hydrogen peroxide vapor concentration. 13 As in the case of UV treatment, some information has cast doubt on the number of cycles allowed while maintaining the integrity of the fit testing after more than two wear sessions. 19 The results of our review support and build on previous recommendations for the most viable decontamination methods for N95 FFRs. Concerning decontamination and reuse of FFRs, the Centers for Disease Control and Prevention (CDC) recognizes UVGI, VHP, and moist heat as the most promising potential methods for decontaminating FFRs.

Additionally, the CDC also accept steam treatment and liquid hydroxygen peroxide as promising methods, but with some limitations, and EtO as a promising method but with serious limitations. 6 The Asia Pacific Center for Evidence-Based Healthcare concluded, based on laboratory-based studies, that UVGI, MGS, warm moist heath, and VHP were shown to be effective in reducing either viral or bacterial load while still maintaining the integrity of N95 FFRs. 27 Hamzavi et al. consider that given that many of our health care providers are using substitutes for N95 FFRs that offer very limited degree of protection, using UVGI and repurposing phototherapy devices could be the best practical solution at this time. 28 Also, supporting the findings of our review, VHP and UVGI for decontaminating and reusing N95 respirators are being used at the Duke University Health Systemy 29 and at the University of Nebraska Medical Center, 30 respectively. As an additional contribution, our review provides information about the N95 FFR models tested with each decontamination method, as well as the specific models that had some problem with each decontamination method (Table 1 ).

In conclusion, although all the methods for decontaminating and reusing N95 FFRs have advantages and disadvantages, UVGI and VHP seem to be the most promising methods, based on their reduction of the microbial threat (including SARS-CoV-2) while maintaining the function of N95 FFRs as well as the lack of residual toxicity. Future studies are required in order to establish the efficacy and security of these decontamination methods on different N95 FFR models and the maximum allowed number of cycles of decontamination under different conditions. 17 Substantial reduction in the recovery of pathogens such as Bacillus subtilis spores after exposure to UVGI for as little as 5 minutes 18 Inactivation of influenza A (H1N1), avian influenza A (H5N1), influenza A (H7N9) A/Anhui/1/2013, influenza A (H7N9) A/Shangai/1/2013, MERS-CoV, SARS-CoV, and SARS-CoV-2 10, 19 No significant effect on filter aerosol penetration, filter airflow resistance, fit and seal, odor, discomfort, difficulty in donning, or physical appearance after up to 20 of cycles of decontamination [10] [11] [12] [13] [14] [15] 25 No significant effect on filtration efficiency after 10 cycles of decontamination. 20 Reduction in the strength of the layers of FFR material (at higher UVGI doses)/ (3M 1860, 3M 9210, Gerson 1730, Kimberly-Clark 46727) 15 UVGI efficiency hampered by shadowing produced by the multiple layers of the N95 FFRs/ (all FFR models) 17 UVGI performance can vary among different models of N95 FFRs, different parts of the respirators, distinct types of UVGI, and number of cycles of decontamination Considerable impact on the strap tension of some N95 FFR models (with 20 cycles of decontamination)/ (3M 1860, 3M 1870, Kimberly-Clark PFR) 10 Better reduction in B. subtilis recovery with UV-C than with UV-A/ (3M 8210) 18 UV-treated FFRs were able to withstand 10 cycles of treatment, but efficiency eventually decayed to 93% at 20 cycles, making it unsuitable for N95-grade FFRs by itself/ (3M 8210, 4C Air, Inc. (GB2626 KN95), ESound (GB2626 KN95), Onnuriplan (KFDA KF94)). 20

3M 1860 3M 1870 3M 9211 N95-A N95-B N95-C SN95-D SN95-E SN95-F Complete inactivation of G. stearothermophilus spores following 50 repeated aerosol inoculation/decontamination cycles 21 Complete eradication after a single VHP cycle of 3 aerosolized bacteriophages (T1, T7, and Pseudomonas phage phi-6) 22 Extremely rapid inactivation of SARS-CoV-2 both on N95 and on stainless steel. 19 No significant effects on filtration performance, filter aerosol penetration, fit, and filter airflow resistance after up to 50 cycles of decontamination 21 No vapors potentially toxic to humans nor environmentally hazardous residues as a result of the VHP decontamination process 11 Fragmentation of the elastic material in the straps when stretched (after 30HPV, but not after 10 or 20 VHP cycles)/ (3M 1860) 21 Slight tarnishing of the metallic nosebands/ (all FFR models) 13 Ethylene oxide (EtO) N95 23 No significant affection of filter aerosol penetration or filter airflow resistance of FFRs (after 2 minutes of microwave exposure) [11] [12] [13] 16 No significant reduction in fit, increase in odor, increase in discomfort, or increased difficulty in donning 14 No known health risks to the users 13 models) 11 Partial separation of the inner foam nose cushion and slight melting of the head straps from some FFR samples/ (SN95-E and SN95-D, respectively) 16 Microwave oven irradiation melted samples from one FFR model/ (SN95-E) 13 Filtration material melted in areas adjacent to the metallic nosebands/ (SN95-E) 13 99-100% biocidal efficacy, indicating effective sterilization of Bacillus subtilis spores 18 No significant affection of filter aerosol penetration or filter airflow resistance Tarnishing of the aluminum nosebands/ (all FFR models) 11, 13, 16 Stiffening of the filter media and elastic straps (treatment with 5.25% bleach) 11 Discoloration of the inner nose cushion of one of the three N95 FFRs evaluated/ (SN95-E) 13 Characteristic smell of bleach/ (all FFR models) 13 Oxidation of staples/ (N95-B, N95-C, SN95-E, SN95-F) 16 Dissolution of nose pads/ (SN95-E) 16 Discoloration (yellowing) of inner nose pads/ (N95-A, SN95-E, SN95-F) 16 Discoloration of other areas of the FFR (bleeding of printed ink lettering)/ (SN95-F) 16 Yellowing of the material adjacent to nose pad/ (SN95-E) 16 From the first disinfection, bleach drastically degraded the filtration efficiency/ (3M 8210, 4C Air, Inc. (GB2626 KN95), ESound (GB2626 KN95), Onnuriplan (KFDA KF94)). 20 Satisfactory decontamination of influenza virus on N95 FFRs as measured by a virus culture method 12 No significant affection of filter aerosol penetration of FFRs 12, 16, 19 No significant affection of filter airflow resistance of FFRs 16 No observable physical change in FFRs 16 No clinically significant reduction in fit, increase in odor, increase in discomfort, or increase in difficulty in donning 14 No significant affection of filtration efficiency or pressure after 10 cycles of decontamination. 20 Increase in filtration penetration (at a temperature of 80 °C) 11 More than one cycle of decontamination caused sharp drops in the filtration performance of N95 FFRs/ (3M 9211) 19 N95 FFRs were largely melted and unusable after only 22 minutes of treatment at 160 °C 11 Partial separation of the inner foam nose cushion and slight melting of the head straps from some FFR samples/ (SN95-E and SN95-D, respectively) 16 Extremely rapid inactivation of SARS-CoV-2 both on N95 and on stainless steel 19 Filtration performance of N95 FFRs was not markedly reduced after a single decontamination with 70% ethanol 19 Higher survival of Bacillus subtilis spores than with other decontamination methods/ (3M 8210) 18 More than one cycle of decontamination caused sharp drops in the filtration performance of the ethanol-treated masks/ (3M 9211) 19 From the first disinfection, ethanol drastically degraded the filtration efficiency/ (3M 8210, 4C Air, Inc. (GB2626 KN95), ESound (GB2626 KN95), Onnuriplan (KFDA KF94)). 20

N95-A N95-B N95-C SN95-D SN95-E SN95-F No significant affection of filter aerosol penetration of FFRs 11, 16 No significant affection of filter airflow resistance of FFRs 16 Slight fading of the label ink on the fabric of FFRs (treatment with 6% LHP for 30 minutes) 11 Oxidation of the staples to varying degrees (for those models that use staples)/ (N95-B, N95-C, SN95-E, SN95-F) 16 

Effective sterilization of almost 100% of Bacillus subtilis spores 18 N95 FFRs were deformed, shrunken, stiff, and mottled (for both 15 and 30 minutes of treatment) 11 Marked increase of filter aerosol penetration of FFRs (for both 15 and 30 minutes of treatment) 11 

A novel coronavirus outbreak of global health concern

COVID-19: protecting health-care workers

Infectious Diseases Society of America Guidelines on Infection Prevention for Health Care Personnel Caring for Patients with Suspected or Known COVID-19

Hospital Respiratory Protection Program Toolkit. Resources for Respirator Program Administrators

Pandemic Influenza Preparedness and Response Guidancefor HealthcareWorkers and Healthcare Employers

Occupational Safety and HealthAdministration

Decontamination and Reuse of Filtering Facepiece Respirators

Persistence of the 2009 pandemic influenza A (H1N1) virus on N95 respirators

Transfer of bacteriophage MS2 and fluorescein from N95 filtering facepiece respirators to hands: Measuring fomite potential

Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

Mitigate a Shortage of Respiratory Protection Devices During Public Health Emergencies

Effect of decontamination on the filtration efficiency of two filtering facepiece respirator models

Effectiveness of three decontamination treatments against influenza virus applied to filtering facepiece respirators

Evaluation of five decontamination methods for filtering facepiece respirators

Impact of three biological decontamination methods on filtering facepiece respirator fit, odor, comfort, and donning ease

Effects of Ultraviolet Germicidal Irradiation (UVGI) on N95 Respirator Filtration Performance and Structural Integrity

Evaluation of

Multiple (3-Cycle) Decontamination Processing for Filtering Facepiece Respirators

Ultraviolet germicidal irradiation of influenza-contaminated N95 filtering facepiece respirators

Relative survival of Bacillus subtilis spores loaded on filtering facepiece respirators after five decontamination methods

Assessment of N95 respirator decontamination and re-use for SARS-CoV-2

Can N95 Respirators Be Reused after Disinfection? How Many Times?

Final Report for the Bioquell Hydrogen Peroxide Vapor (HPV) Decontamination for Reuse of N95 Respirators

Hydrogen Peroxide Vapor sterilization of N95 respirators for reuse

Evaluation of microwave steam bags for the decontamination of filtering facepiece respirators

Cleaning of filtering facepiece respirators contaminated with mucin and Staphylococcus aureus

Amendment 1 -Limited Study Evaluating UVGI-Treated FFR Odor

A method to determine the available UV-C dose for the decontamination of filtering facepiece respirators

What are the effective methods of decontaminating N95 mask for reuse? Asia Pacific Center for Evidence Based Healthcare

Abdriged-IGC-AM-02Apr-2020.pdf (Accesed at

Ultraviolet germicidal irradiation: Possible method for respirator disinfection to facilitate reuse during the COVID-19 pandemic

Decontamination and Reuse of N95 Respirators with Hydrogen Peroxide Vapor to Address Worldwide Personal Protective Equipment Shortages During the SARS-CoV-2 (COVID-19) Pandemic

The authors thank Mr. Charlie Barret for his editorial assistance.

Isopropyl alcohol N95