Abstract and Introduction
Abstract
Purpose: The efficacy of hydrogen peroxide and peracetic acid as isolator sterilization agents was compared.
Methods: Sterilization and efficacy tests were conducted in a flexible 0.8-m transfer isolator using a standard load of glass bottles and sterile medical devices in their packing paper. Bacillus stearothermophilus spores were placed in six critical locations of the isolator and incubated at 55 ºC in a culture medium for 14 days. Sterilization by 4.25 mL/m of 33% vapor-phase hydrogen peroxide and 12.5 mL/m of 3.5% peracetic acid was tested in triplicate. Sterility was validated for hydrogen peroxide and peracetic acid at 60, 90, 120, and 180 minutes and at 90, 120, 150, 180, 210, and 240 minutes, respectively.
Results: In an efficacy test conducted with an empty isolator, the sterilization time required to destroy B. stearothermophilus spores was 90 minutes for both sterilants, indicating that they have comparable bactericidal properties. During the validation test with a standard load, the sterilization time using hydrogen peroxide was 150 minutes versus 120 minutes with peracetic acid. The glove cuff was particularly difficult for hydrogen peroxide to sterilize, likely due to its slower diffusion time than that of peracetic acid. Hydrogen peroxide is an environmentally safer agent than peracetic acid; however, its bacteriostatic properties, lack of odor, and poor diffusion time may limit its use in sterilizing some materials.
Conclusion: Hydrogen peroxide is a useful alternative to peracetic acid for isolator sterilization in a hospital pharmacy or parenteral nutrition preparation unit.
Introduction
In French hospitals, the pharmacy department aseptically prepares parenteral nutrient solution, made of commercially available solutions of amino acids, lipids, glucose, and sodium chloride. The solution is prepared in accordance with the Good Practices of Hospital Preparations, which requires the use of a barrier isolator.
Isolators work on two principles: confinement and transfer. An isolator is a closed and tight bubble with a physical barrier preventing contact between the compounded sterile preparation and outside air. It also has an autonomous ventilation system equipped with a high-efficiency particulate air (HEPA) filter (ISO class 5) and a transfer chamber to protect the sterile atmosphere from any outside contamination. One unit is often made up of several isolators. It is possible to connect and disconnect them without compromising the sterile environment. Large principal isolators, such as the one in Figure 1, are used for the aseptic preparation of solutions to be stored in bags or syringes. Manipulation is performed using gloves or a half-suit. A transfer isolator provides additional isolator space for the introduction of raw materials into the main isolator (Figure 2). Isolators must be in a room with a controlled atmosphere (ISO class 8).
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Figure 1.
A principal isolator connected to a transfer isolator.
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Figure 2.
Transfer isolator.
Several methods of sterilization can be used with isolators. Chemical sterilization with vapor-phase hydrogen peroxide (VPHP) or peracetic acid is the most commonly used method. Lysfjord and Porter examined the isolator sterilization methods of 80 pharmaceutical manufacturing plants and found that 72 used VPHP and 8 used peracetic acid.
VPHP is an effective surface decontaminant at low temperatures. VPHP can only sterilize surfaces that fit in the isolator, and the contact time increases with the amount of materials to be sterilized. VPHP is particularly effective for sterilizing smooth surfaces, such as glass or metal. The European Pharmacopoeia recommends the use of Bacillus stearothermophilus to validate the sterilization method since it is the bacteria most resistant to VPHP and peracetic acid. B. stearothermophilus spores have been found to be more resistant to VPHP than Bacillus subtilis spores. The culture time is approximately 14 days.
Both hydrogen peroxide and peracetic acid are toxic substances. Hydrogen peroxide has oxidizing and radical generator properties and can irritate eyes, mucous membranes, and skin. Deep inhalation of VPHP can induce acute pulmonary edema. Inhalation of highly concentrated vapor may cause extreme nose and throat irritation. Severe systemic poisoning may cause headache, dizziness, vomiting, diarrhea, tremors, numbness, convulsions, pulmonary edema, unconsciousness, and shock. The current Occupational Safety and Health Administration permissible exposure limit for hydrogen peroxide is 1 ppm parts of air (1.4 mg/m) as an eight-hour time-weighted average concentration. Genotoxic and teratogenic effects also have been demonstrated in animals with oral administration of hydrogen peroxide. No studies have reported any possible mutagenic, genotoxic, or teratogenic effects of hydrogen peroxide in humans. No adequate data have demonstrated the carcinogenicity of hydrogen peroxide in humans, and only limited data exist regarding its carcinogenicity in mice.
Peracetic acid is toxic because of its acidic, oxidative, and radical generator properties. In animals exposed to the agent, skin, mucous membrane, and respiratory irritations have been observed. Animals chronically exposed to peracetic acid have demonstrated weight loss and an increase in mortality. The genotoxic and teratogenic effects have been demonstrated in vivo with parenteral administration. However, it is not carcinogenic with cutaneous administration. Few data on human toxicity have been published, but some reports have noted nose and eye irritation after chronic exposure (0.005-1.84 mg/m) and after acute exposure (3-8 mg/m). Currently no standards regulate the amount of peracetic acid to which someone should be exposed. Further, no recommendations have been made by the National Institute for Occupational Safety and Health or the American Conference of Governmental Industrial Hygienists.
Peracetic acid and hydrogen peroxide have similar toxicity profiles. Peracetic acid has been shown to be less mutagenic than hydrogen peroxide in vitro. Both agents should be used with extreme caution and require the use of materials protection. In Europe, peracetic acid is considered the standard for sterilizing isolators in hospitals. Nevertheless, hydrogen peroxide has the advantage of being environmentally safe because its decomposition in oxygen and water is better than that of acid residues.
Our pharmacy is equipped with a vapor generator that can use both agents to sterilize isolators. Although isolators are sterilized with peracetic acid in our hospital, we compared sterilization efficacy and the practical use of peracetic acid and hydrogen peroxide in a hospital pharmacy.