Vaporized hydrogen peroxide is a common gaseous sterilant widely used in industry and it has been found to be an effective chemical warfare agent decontaminant in the presence of ammonia for SM and nerve agents (Wagner et al., 2007).
From: Handbook of Toxicology of Chemical Warfare Agents, 2009
Material and process compatibility testing
Brian K Meyer, in Therapeutic Protein Drug Products, 2012
4.2.8 Hydrogen Peroxide
Due to the increased use of barrier isolator systems that utilize vaporized hydrogen peroxide for sterilizing equipment, the potential impact of this molecule should be evaluated with the therapeutic protein. Residual hydrogen peroxide in process materials such as tubing or other equipment could impact the product. Examples of how hydrogen peroxide impacts proteins were recently explored with parathyroid hormone (Ji et al., 2009). Testing for the effects of hydrogen peroxide on the therapeutic protein may be performed by spiking hydrogen peroxide followed by analysis to evaluate oxidation. One common method to evaluate oxidation of therapeutic proteins is mass spectroscopy.
Non-traditional sterilization techniques for biomaterials and medical devices
S. Lerouge, in Sterilisation of Biomaterials and Medical Devices, 2012
5.3.4 Vaporized chemical sterilant systems
To overcome the limitations of liquid sterilization, sterilizers using vaporized hydrogen peroxide (VHP) were proposed in the mid-1980s, using various technologies to transform liquid H2O2 (around 30–35% concentration) into vapor and delivering it in the chamber. One method uses a deep vacuum to pull liquid hydrogen peroxide from a disposable cartridge through a heated vaporizer and then, following vaporization, into the sterilization chamber. In another approach, VHP is brought into the sterilization chamber by a carrier gas such as air using either a slight negative pressure (vacuum) or slight positive pressure. Applications of this technology include vacuum systems for industrial sterilization of medical devices and atmospheric systems for decontamination of large and small areas (French et al., 2004). VHP has several advantages: rapid cycle time (e.g. 30–45 min), low temperature, environmentally safe by-products (only water and oxygen), relatively good material compatibility and ease of operation, installation and monitoring. However, it also has limitations, mainly lower penetration capabilities when compared with EO. It also shares Sterrad® incompatibility with cellulose and nylon. In fact, these systems are very close to Sterrad® systems, without the advantage of elimination of H2O2 by plasma, but with the advantage of larger chambers that enables to process more devices at the same time. Further investigation of this method is required to demonstrate both safety and effectiveness. VHP has not yet been cleared by FDA for sterilization of medical devices in healthcare facilities (Rutala, 2008). Similarly, vaporized peracetic acid has also been recently proposed, but is not yet cleared.
Assessing, Controlling, and Removing Contamination Risks From the Process
Tim Sandle, in Biocontamination Control for Pharmaceuticals and Healthcare, 2019
The most widely used method of biodecontamination is the application of hydrogen peroxide in the vapor state. This is sometimes referred to as a sterilization method. However, it has no penetrative ability and thus a safer term is “biodecontamination.” The inference of this is with activities like aseptic processing, if an isolator is subject to a hydrogen peroxide cycle then items which are required to be sterile, such as a stopper bowl, must be subject to a separate method of sterilization and aseptically transferred into the isolator.
Vaporized hydrogen peroxide (VHP) is a broad-spectrum antimicrobial with virucidal, bactericidal, fungicidal, and sporicidal activity. VHP is a relatively rapid sterilization technology. VHP is produced by the vaporization (at 120°C) of liquid hydrogen peroxide to give a mixture of VHP and water vapor. As a “dry” process, the concentration of VHP is maintained below a given condensation point, which is dependent on the area temperature. Its advantage over other gaseous technologies is that it decomposes to water and oxygen, which are relatively safe and so-termed residue free (Kokubo, Inoue, & Akers, 1998).
VHP processes also have prerequisites in terms of the physical properties of the items being treated: they must be relatively smooth, impervious to moisture, and be of a shape that permits all surfaces to be exposed to the sterilant.
Disinfection, Sterilization, and Control of Hospital Waste
William A. Rutala, David J. Weber, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), 2015
Vaporized Hydrogen Peroxide
A new low temperature sterilization system uses vaporized hydrogen peroxide to sterilize reusable metal and nonmetal devices used in health care facilities. The system is compatible with a wide range of medical instruments and materials (e.g., polypropylene, brass, polyethylene). There are no toxic by-products because only water vapor and oxygen are produced. The system is not intended to process liquids, linens, powders, or any cellulose materials. The system can sterilize instruments with diffusion-restricted spaces (e.g., scissors) and medical devices with a single stainless steel lumen based on lumen internal diameter and length (e.g., an inside diameter of 1 mm or larger and a length of 125 mm or shorter; see manufacturer's recommendations). Thus, gastrointestinal endoscopes and bronchoscopes cannot be sterilized in this system at the current time. Although this system has not been comparatively evaluated with other sterilization processes, vaporized hydrogen peroxide has been shown to be effective in killing spores, viruses, mycobacteria, fungi, and bacteria. Table 301-3 lists the advantages and disadvantages of this and other processes.
A guide to no-touch automated room disinfection (NTD) systems
J.A. Otter, ... G.L. French, in Decontamination in Hospitals and Healthcare, 2014
H2O2 vapour systems deliver a heat-generated vapour of 30–35% w/w aqueous hydrogen peroxide through a high-velocity air stream to achieve homogeneous distribution throughout an enclosed area (enclosure) (Fig. 17.4) (Boyce, 2009; Otter and Yezli, 2011). Two systems using H2O2 vapour are available commercially – Bioquell and Steris. Bioquell systems are usually termed hydrogen peroxide vapour (HPV) and Steris systems vaporized hydrogen peroxide (VHP). Bioquell HPV includes a generator to produce HPV, a module to measure the concentration of HPV, temperature and relative humidity in the enclosure and an aeration unit to catalyse the breakdown of HPV to oxygen and water vapour after HPV exposure. A control pedestal is situated outside the enclosure to provide remote control. Bioquell HPV is delivered until the air in the enclosure becomes saturated and H2O2 begins to condense on surfaces (Hall et al., 2007; Ray et al., 2010). Steris VHP systems have a generator inside the room with an integral aeration unit and dehumidifier designed to achieve a set humidity level prior to the start of the cycle. The system is controlled remotely from outside the enclosure. Steris VHP systems deliver ‘non-condensing’ VHP by drying the vapour stream as it is returned to the generator. Bioquell systems do not control the H2O2 air concentration while the Steris systems hold a steady H2O2 air concentration throughout the exposure period.
Nalini Singh, Karl Klontz, in Principles and Practice of Pediatric Infectious Diseases (Fifth Edition), 2018
Meticulous hand hygiene with soap and water should be performed before and after donning gloves when any contact is expected with patients infected with C. difficile. All healthcare personnel should use glove and gown precautions when in contact with the patient and the surrounding environment.61,62 Waterless gel is ineffective in killing spores of C. difficile. Cases of healthcare-associated CDAD in healthcare personnel have occurred. Children with CDAD should not attend out-of-home childcare facilities while symptomatic with diarrhea.
Environmental contamination plays an important role in the transmission of C. difficile.28 C. difficile has been transmitted through electronic thermometers.63 Endoscopes have not been implicated in C. difficile transmission. The degree to which the environment becomes contaminated is proportionate to the patient's severity of disease. Diluted sodium hypochlorite successfully eradicates spores, whereas routine hospital cleaning agents such as quaternary ammonium compounds are ineffective. Vaporized hydrogen peroxide delivered through a special apparatus is successful in reducing environmental contamination of C. difficile.64 This procedure can be carried out in vacant hospital rooms and requires that the room be sealed off to ensure efficacy and avoid inadvertent exposure to patients. The effectiveness of this technology needs further evaluation. Comprehensive strategies to prevent C. difficile that include antimicrobial stewardship have been published.65 A promising first-in-human phase 1 vaccine trial in adults using toxoid antigens was published in 2016.66
Diagnosis and Management of Clostridium difficile Infection
• Acquired from infected people or contaminated environments, especially healthcare environments
• Evolving from healthcare-associated to community-acquired infection
• Exposure to antibiotic therapy a risk factor for developing disease
• Neonates can be colonized without symptomatic illness.
• Most commonly manifesting as mild to moderate diarrhea with or without mucus or blood in stool
• Pseudomembranous colitis
• Complications including toxic megacolon, intestinal perforation, sepsis, ascites, intussusception, and pneumatosis intestinalis
• Detection of C. difficile toxins
o Two-step enzyme immunoassay first to detect glutamate dehydrogenase (sensitive but nonspecific) and then to detect toxin if step 1 is positive
o Stand-alone nucleic acid amplification test
• Discontinuation of precipitating antibiotic
• Initial infection:
o Mild to moderate disease: oral metronidazole 30 mg/kg/day in 4 divided doses, maximum 2 g/day
o Severe disease, as in patients who are in an intensive care unit, have proven pseudomembranous colitis, have underlying intestinal disease, or are unresponsive to metronidazole therapy: oral vancomycin 40 mg/kg/day in 4 divided doses, maximum 2 g/day
o Severe disease with shock, ileus, or megacolon: vancomycin enema and intravenous metronidazole
o Duration of therapy a minimum of 10 days
• First relapse: same regimen as the initial episode
• Second or later relapse: oral vancomycin in therapeutic and then tapered or pulsed therapy are recommended. Metronidazole should not be used for treatment of a second recurrence because neurotoxicity is possible.
• Fidaxomicin approved for treatment in adults
Sterilisation considerations for implantable sensor systems
S. Martin, E. Duncan, in Implantable Sensor Systems for Medical Applications, 2013
8.3.5 Alternative sterilisation methods: considerations for implantable sensor systems
Other less conventional, less frequently used methods may be considered as suitable alternatives for implantable sensor systems, because these systems have different performance and risk priorities compared with large volume, low cost disposable medical devices. When protecting the performance of the implantable sensor is critical, neither extra time nor cost will prevent these alternative sterilisation processes from being the method of choice.
Vaporised hydrogen peroxide (VHP) sterilisation is a low-temperature gaseous method of sterilisation. Compared to EO gas, VHP typically cannot penetrate large, dense packaging, but it can offer an alternative where material compatibility with EO is a problem. Because hydrogen peroxide breaks down to water and oxygen, aeration time is greatly reduced and any concern for toxicity is very low risk. The FDA has granted 510(k) clearance for the use of various models of vapour sterilisation systems to terminally sterilise medical devices (K083097;6 K0713857). However, when used in an industrial setting, the sterilisation equipment and support systems must undergo installation, operations and sterilisation validation which can be time-consuming and costly. To date, these constraints have retarded the widespread use of the VHP sterilisation method, but the process and chemistry are relatively more compatible with the materials, making this a suitable alternative for implantable sensor systems.
Numerous other chemical sterilisation systems that create penetrating vapours currently have limited availability or are still under development and qualification. Chemical sterilants such as ozone, nitrogen dioxide and supercritical carbon dioxide may encounter constraints for validation of sterility because the commercial sterilisation indicators are not as widely available, and fewer laboratories are trained in their use (Lambert, 2010). One very popular peracetic acid sterilisation system for endoscopes and devices that are sensitive to moisture and radiation, Steris 1, is now under mandatory recall by the FDA (Steris 1 peracetic acid sterilisation system recall8). Such large scale recalls can make manufacturers nervous about adopting new technologies, even when the systems have had FDA clearance to market.
Liquid chemical sterilants (also known as germicides) such as ortho-phthalaldehyde (OPA) are now in use in Europe and the USA and have been shown to have superior mycobactericidal activity compared with glutaraldehyde (New Disinfection and Sterilization Method: Ortho-phthalaldehyde: a New Chemical Sterilant9). These sterilants do not irritate the eyes and nasal passages as much as glutaraldehyde. Although OPA has good materials compatibility, it stains proteins grey. Colour changes in materials as a result of sterilisation are often perceived as undesirable characteristics, particularly if the colour change makes the product look dirty even if there is no effect on device function. To cover up the colour change, manufacturers sometimes add pigments, further complicating the qualification of the product in terms of biocompatibility. Furthermore, disposal of spent OPA requires special precautions, which can add to the cost of processing the product. Any sensor manufacturer hoping to use this chemical steriliser would of course have to conduct extensive testing on the implantable sensor system to rule out potential effects of the chemical on the sensor output. Without experience of the chemistries involved it could be difficult to anticipate the various modes of failure.
Sterilox is super-oxidised water, made from saline, and effective against a wide range of organisms (K07138510). Although described as not damaging to the environment, the most active component is hypochlorous acid. Its compatibility to many medical device materials has not yet been demonstrated. The sterilisation system can be corrosive to certain materials but is non-toxic to biological tissues.
Aseptic processing standards are being developed for medical devices to eventually enable greater acceptance of devices where processing procedures attempt to maintain sterility of the device throughout the manufacturing process to the point of use. Aseptic manufacturing means that the components and materials that comprise a device are pre-sterilised appropriately and all materials, equipment and support systems are used only after sterilisation. All working steps are performed in clean areas to avoid contamination. For such processing, only the highest standards of purity and cleanliness for the manufacturing room, the personnel, the equipment, and the supply of air, water, sterile gases and materials used in the working process must be maintained at all times. Maintaining such control is usually prohibitively expensive for medical devices.
Dry-heat sterilisation has been available for decades (Darmady et al., 1961), but has limited commercial uses due to the considerations of material impact from the high temperatures (170–180 °C) and time (cycles of an hour or longer). It has increasing interest for instrumentation because packaging materials that can withstand dry-heat sterilisation have become available. Its utility for implantable sensors made with polymers is unlikely due to the high temperature.
Many different alternative sterilisation methods are available. The design, materials and limited environmental functional range of implantable sensor systems may require the use of these alternative sterilisation methods despite their obvious drawbacks if conventional sterilisation methods simply do not work.
Etiologic Agents of Infectious Diseases
Nalini Singh, David Y. Hyun, in Principles and Practice of Pediatric Infectious Diseases (Fourth Edition), 2012
Meticulous hand hygiene with soap and water should be performed before and after donning gloves when any contact is expected with patients infected with C. difficile. All healthcare personnel (HCP) should use glove and gown precautions when in contact with the patient and the surrounding environment.58,59 Waterless gel is ineffective in killing spores of C. difficile. Cases of HA-CDAD in HCP have occurred. Children with CDAD should not attend out-of-home childcare facilities while symptomatic with diarrhea.
Environmental contamination plays an important role in the transmission of C. difficile.28 C. difficile has been transmitted via electronic thermometers.60 Endoscopes have not been implicated in C. difficile transmission. The degree to which the environment becomes contaminated is proportionate to the severity of disease in the patient. Diluted sodium hypochlorite successfully eradicates spores whereas routine hospital cleaning agents such as quaternary ammonium compounds are ineffective. Vaporized hydrogen peroxide delivered via a special apparatus is successful in reducing environmental contamination of C. difficile.61 This procedure can be carried out in vacant hospital rooms and requires that the room be sealed off to ensure efficacy and avoid inadvertent exposure to patients. The effectiveness of this new technology needs further evaluation. Antimicrobial stewardship programs promoting judicious use of antimicrobial agents can also reduce the risk of CDAD.62
Diagnosis and Management of Clostridium difficile Infection
• Acquired from infected individuals or contaminated environments, especially healthcare environments
• Evolving from healthcare-associated to community-acquired disease
• Exposure to antibiotic therapy is a risk factor for developing disease
• Neonates can be colonized without symptomatic illness
• Most commonly manifests as mild to moderate diarrhea with or without mucous or blood in stool
• Pseudomembranous colitis
• Complications include toxic megacolon, intestinal perforation, sepsis, ascites, intussusception, and pneumatosis
• Detection of C. difficile toxins
• Enzyme immunoassay (EIA) kits for toxins A and B
• Cell culture cytotoxicity assay is gold standard but associated with high cost and slow turnaround time
• Culture isolation of C. difficile cannot distinguish between toxigenic and nonpathogenic colonizing strains
• Two-step identification of organism's glutamate-dehydrogenase (GDH) antigen, followed by EIA toxin assay if GDH positive, holds promise because of rapidity and high predictive values
• Discontinuation of precipitating antibiotic
• Initial infection:
o Mild to moderate disease: oral metronidazole (30 mg/kg/day in 4 divided doses, max. 2 g/day)
o Severe disease in patients who have underlying intestinal disease, or are unresponsive to metronidazole therapy, or are critically ill: oral vancomycin (40 mg/kg/day in 4 divided doses, max. 125 mg/dose)
o Severe disease with shock, ileus, or megacolon: oral vancomycin and intravenous metronidazole
o Duration of therapy is minimum of 10 days
• Relapse infection:
o First relapse: same regimen as the initial episode
o Second or later relapse: oral vancomycin in therapeutic and then tapered or pulsed therapy
Bacillus anthracis (Anthrax)
Gregory J. Martin, Arthur M. Friedlander, in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), 2015
One of the more controversial topics regarding bioterrorist-associated use of anthrax is the method and cost associated with making spore-contaminated areas safe. Clearly, this is an additional advantage to the terrorist of using an agent that has the demonstrated persistence of the anthrax spore. During the massive cleanup effort in the wake of the 2001 attacks, there has been increased understanding of decontamination of spores that has continued during the remainder of the decade. The Environmental Protection Agency has outlined eight steps in the remediation process of contaminated sites that are presented in Table 209-9.125
Fortunately, one of the least expensive and most commonly available compounds used to destroy anthrax spores is household bleach, and many of the high-tech remediation methods use chloride in some manner. Bleach, chlorine dioxide, ethylene oxide, hydrogen peroxide, peroxyacetic acid, methyl bromide, paraformaldehyde, and vaporized hydrogen peroxide were all used to some degree in the federal decontamination process in 2001 and 2002.167 As might be expected, one agent is not suitable for all applications. Chlorine dioxide gas and liquid were used extensively in the U.S. Capitol's Hart Senate Office Building but were not found to be very effective for porous surfaces such as carpeting, chairs, and fabric surfaces, which were subsequently decontaminated with other agents.
In the event of widespread contamination of individuals and households where the public will be expected to be performing much of the decontamination efforts, it is likely that household bleach in 1 : 10 dilution will be recommended because it is readily available. Contaminated individuals should be advised to remove clothing and place it in a bag either before entering their home or immediately after entering (to minimize spores coming off clothes into the home). They should shower using soap and water and shampoo their hair. Clothes can be decontaminated by washing in hot water with bleach and machine drying. Dry cleaning will also destroy spores.
How extensively remediation must be performed remains controversial. Because it is well-known from studies of wool mill workers and nonhuman primates that the innate immune system can eradicate an as yet undefined number of spores, preventing the development of inhalational anthrax, must every spore be removed from every surface? There may be an acceptable level of contamination that will allow for a timelier and cost-effective remediation effort after a citywide exposure without serious compromise to the public health of the community. The National Academy of Sciences reviewed remediation of buildings after anthrax contamination and addressed many of these controversial areas but concluded that it cannot be determined what lowest level of spore contamination is acceptably safe for exposure.168