Hydrogen Peroxide Emission Problems from Sterilizers

The previous ChemDAQ blog discussed continued off-gassing of plastic parts sterilized in a hydrogen peroxide sterilizer as reported by Rika Yoshida, Hiroyoshi Kobayashi at a recent conference of the World Formum for Sterile Hospital Supply. This presentation also discussed hydrogen peroxide vapor emissions from hydrogen peroxide sterilizers. The sterilizers included several models of Sterrad^® sterilizer from Advanced Sterilization Products, and the V-Pro1^TM from Steris. The authors have also published some of these results in the Japanese Journal of Environmental Infections, and a full text copy of their paper is available.

The investigators measured the hydrogen peroxide concentration inside a sterilizer immediately after the end of the cycle, when people would be reaching in to remove the load, and found very high concentrations (34 ppm Sterrad 100S; 60 ppm Sterrad 200; and 13 ppm V-Pro1) in some cases close to the NIOSH Immediately Dangerous to Life and Health value of 75 ppm. Since the time to unload a sterilizer is fairly short, a single exposure will probably not exceed the OSHA PEL of 1 ppm calculated as a time weighted average over 8 hours, but it would probably exceed the 3 ppm 15 minute short term exposure limit found in some states (Washington and Hawaii) and even the OSHA PEL may be reached in a busy facility for someone running multiple loads a day.

ChemDAQ has received many reports from users of hydrogen peroxide emissions when the sterilizer door is opened at the end of a cycle. In a typical ChemDAQ installation the sensor is placed on top of the sterilizer and so the concentration measured will be much lower than would measured from a sensor placed inside the sterilizer chamber because the vapor gets diluted by the time it reaches the sensor.

Users often see small increases in hydrogen peroxide concentration, usually less than 1 ppm, though one model of sterilizer was found to emit much higher concentrations (~30 ppm) each time the door was opened. In this case, the hospital had four sterilizers, all new, all showing the same behavior. The manufacturer was unable to solve the problem and the hospital now instructs their technicians to open the sterilizer door at the end of the cycle and leave the area until the ChemDAQ monitor shows that it is safe to return.

Rika Yoshida, Hiroyoshi Kobayashi began their investigation in response to complaints of eye and respiratory system irritation from healthcare workers using hydrogen peroxide sterilizers. There are many similar reports of eye and respiratory system irritation from hydrogen peroxide sterilizers in the FDA’s MAUDE database and so it is likely that the results reported in their paper are not unique.

For many years ChemDAQ has been pointing out that all sterilant chemicals are potentially hazardous since they are designed to kill all microorganisms and therefore we recommend that all sterilant gases and vapors should be monitored.

Plastic Parts Off-Gas Hydrogen Peroxide Vapor After Sterilization

Ethylene oxide (EtO) as a sterilant gas has two main drawbacks; the first is health – EtO is an irritant and a carcinogen and the second is economic; a typical EtO sterilization cycle may take 12 to 15 hours. While the actual sterilization step may only last a couple hours, the rest of the time is needed for the sterilized product to aerate and give up the EtO trapped within it.

Since the mid 1990s many alternative gases and vapors have been explored as low temperature gas or vapor sterilants. Obviously none of them are harmless since sterilization is achieved by exposing the device to high concentrations of reactive gases. Typical gases used are hydrogen peroxide or ozone, both strong oxidants, and formaldehyde (steam formaldehyde), an alkylating agent similar to EtO (not currently used in the US).

In addition to avoiding EtO, the main selling features of hydrogen peroxide sterilization have been the short cycle times. The two leading manufacturers of hydrogen peroxide sterilizers, Advanced Sterilization Products and Steris Corporation, both now offer cycles times as short as 28 minutes. These features have been so attractive that hydrogen peroxide sterilization is now the dominant form of low temperature gas sterilization used in the US today.

The conventional wisdom is that EtO has a long cycle time because porous and some plastic products dissolve or otherwise retain the EtO and the long cycle time is required to allow the EtO to diffuse out of the product; whereas for hydrogen peroxide little or no aeration time is required.

A recent study by Japanese researchers from the Division of Infection Prevention and Control, Tokyo Healthcare University Postgraduate School challenged the conventional wisdom by showing that some plastic devices after hydrogen peroxide sterilization, off-gas the hydrogen peroxide vapor and take a much longer time for the vapor to clear than some of the current hydrogen peroxide sterilization cycles allow.

The researches took 11 kinds of plastic test panels, made of the polymers common used to manufacture medical devices and sterilized them using a hydrogen peroxide sterilizer and then measured the hydrogen peroxide vapor off-gassing from the surface of the plastics. They found that some plastics retained the hydrogen peroxide for much longer than others. A similar effect is seen with EtO, where some polymers such as PVC are notorious for slowly releasing dissolved EtO. The initial concentration of hydrogen peroxide emitted ranged from ~40 to over 300 ppm and many of the plastic panels with the initially higher hydrogen peroxide continued to emit concentrations over 50 ppm more than 25 minutes later.

In another test, the researches took a medical stapler made of polyetherimide, sterilized it, and found that the stapler initially emitted over 300 ppm hydrogen peroxide and took six days for the emitted hydrogen peroxide concentration to fall to 10 ppm, and 24 days before the concentration fell below 1 ppm (the OSHA PEL). In another test, flexible scopes continued to out gas hydrogen peroxide above 10 ppm for 18 to 40 hours.

The researchers started the work in response to complaints or eye and respiratory system irritation from healthcare workers who work around the sterilizers but the use, clean & sterilize and reuse times of many devices such as flexible scopes is often much less than 40 hours and so the researchers went to comment that healthcare workers should be on the look out for adverse effects in patients (as well as in their colleagues performing the sterilization).

The conventional wisdom is that hydrogen peroxide sterilization is much superior to EtO sterilization in large part because the latter does not require long aeration periods and so can perform its sterilization function with short cycles which saves time and resources as equipment can be sterilized and put back into service more quickly. This study by Rika Yoshida, Hiroyoshi Kobayashi directly challenges the belief that there is no significant out-gassing with hydrogen peroxide and shows that the concentrations being emitted are not only above the OSHA PEL (1 ppm 8 hr TWA), but in some cases over the NIOSH Immediately Dangerous to Life and Health level (75 ppm). These results parallel a study from 1997 by MacNeal and Glaser ["Comparison of healthcare based sterilization technologies: Safety, efficacy, and economics" in Journal of Healthcare Safety, Compliance & Infection Control (1997), 1,(2, December), p 91 to 107] where they found that

"Packages removed from the sterilizer after on hour continued to emit residual H2O2 gas at short-term or instantaneous concentrations of up to 2.5 ppm, for up to 1.3 hours following their removal from ther sterilizer."

Surprisingly, there do not appear to have been any other studies that looked at out-gassing of hydrogen peroxide from sterilized medical devices, though with the questions raised by these two research groups, we are sure that much more attention will be given to this important subject going forward.

New Food Production Requirements from the FDA

The Food and Drug Administration (FDA) has taken steps to reduce the number of food borne illnesses. Most food borne illnesses are caused by bacteria, though infections due to norovirus are also very common. The CDC estimates that each year roughly 1 in 6 Americans (or 48 million people) gets sick, 128,000 are hospitalized, and 3,000 die of foodborne diseases.

On January 4th, the FDA issued a press release announcing two new rules intended to reduce food borne illnesses implementing changes under the Food Safety Modernization Act (FSMA).

The first rule applies to food manufacturers, packers and handlers and takes a ‘Quality Assurance’ approach by amending the FDA's Current Good Manufacturing Practice. The new rule requires food manufacturers and handlers to implement an improved quality program that includes “implement hazard analysis and risk-based preventive controls for human food.” These preventive controls would include requirements for covered facilities to maintain a food safety plan, perform a hazard analysis, and institute preventive controls for the mitigation of those hazards. Further details including the exemptions from these requirements can be found in the text of the proposed rule

In the second rule the FDA is proposing to establish science-based minimum standards for the safe growing, harvesting, packing, and holding of produce, meaning fruits and vegetables grown for human consumption. There are several aspects to this rule:

• Worker Training and Heath and Hygiene: Establish qualification and training requirements for all personnel who handle (contact) covered produce or food-contact surfaces and their supervisors, document the training and establish hygienic practices and other measures needed to prevent persons, including visitors, from contaminating produce.
• Agricultural Water: Require that all agricultural water, i.e. water intended to, or likely to, contact the harvestable portion of covered produce or food-contact surfaces, is shown by testing to be safe and sanitary quality for its intended.
• Prohibit use of human waste as fertilizer and limit use of animal waste as fertilizer and limit access of grazing animals to land where food is grown/produced.
• Establish cleaning/sanitizing standards for equipment used to process food crops and prevent contamination from workers, toilets, animal waste etc.
• Additional procedures and water quality tests for sprouts.

Further details and those produces who are exempt from these regulations can be found in the text of the proposed rule. The public is invited to comment over the next 120 days on these proposed rules.

Turf Wars in Healthcare Regulation; EPA, OSHA and FDA.

At first glance the Environmental Protection Agency (EPA), Food and Drug Administration (FDA) and the Occupational Safety and Health Administration (EPA) are very different, but the purview of all three agencies overlaps in healthcare. OSHA is concerned with workplace safe, the FDA with drug and medical device safety for patients and the EPA with environmental safety and control of pesticides.

A disinfectant such as peracetic acid (PAA) is regulated by the EPA as a pesticide, but if the peracetic acid is being used to disinfect an endoscope it now falls under the FDA.

Exposure of hospital cleaning personnel to blood and other biological waste, especially those folks who have to ‘clean up the mess’ is a serious health risk and is addressed by OSHA’s Blood Borne Pathogen Standard 29 CFR 1910.1030 and OSHA requires the use of an appropriate cleaner.

   Contaminated work surfaces shall be decontaminated with an   appropriate disinfectant after completion of procedures;   immediately or as soon as feasible when surfaces are overtly   contaminated or after any spill of blood or other potentially   infectious materials; and at the end of the work shift if the   surface may have become contaminated since the last cleaning.   1910.1030(d)(4)(ii)(A)

So now, three agencies have potential jurisdiction over biocides.

It is the EPA’s function under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) to regulate pesticides and therefore it is up to the EPA to approve antimicrobial cleaners and the EPA maintains a list of approved disinfectants effective against certain blood borne/body fluid pathogens, Mycobacteria tuberculosis (tubercle bacteria), human HIV-1 virus, Hepatitis B, Hepatitis C viruses, as well as products classified as sterilizers. OSHA's 'appropriate cleaner' refers to the EPA list. The EPA also maintains a list of approved sterilant chemicals, such as ethylene oxide and hydrogen peroxide used to sterilize medical devices.

Generally workplace exposure to chemicals is regulated by OSHA, explicitly through its permissible exposure limits (PELs) and indirectly through the General Duty Clause of the 1970 Occupation Safety and Health Act. The EPA does not regulate workplace exposure guidelines, that is OSHA’s job, but the EPA will issue Acute Exposure Guidelines for some pesticides, especially those that OSHA has not issued PELs, such as peracetic acid. The AEGLs also differ from OSHA PELs in that the former refer to repeated exposure, whereas the AEGLs are for one off or occasional exposure.

The EPA and OSHA have issued several Memorandums of Understanding (MOUs to improve working relationships between the two government agencies. The MOUs say that the agencies will share phone numbers, share data, and generally work together.

The FDA and the EPA also have some overlapping jurisdiction, especially for high level disinfectants and sterilant chemicals. The FDA and EPA also have several MOUs discussing common areas of interest from food to drugs. There is a 1993 MOU concerning high level disinfectants and sterilants, in which the roles of the two agencies are delineated.

• FDA will be primarily responsible for the premarket review of safety and efficacy requirements for liquid chemical germicides that are sterilants intended for use on critical or semicritical devices. Examples of critical devices are laparoscopes, surgical instruments, heart-lung oxygenators, and transfer forceps. Examples of semicritical devices are gastrointestinal endoscopes, endotracheal tubes, cystoscopes, anesthesia breathing circuits, and vaginal specula FDA will also be primarily responsible for premarket review of contact lens solutions.

• EPA will be primarily responsible for premarket review of liquid chemical germicides that are general purpose disinfectants intended for use on devices other than critical or semicritical devices. Examples of noncritical devices are wheel chairs, medical beds, stands, certain operating room surfaces, medical lamps, dental units, and stethoscopes. …

Anytime there is overlapping jurisdiction there will be some friction and conflict; which causes delays, uncertainty and extra work for manufacturers and to a lesser extent users. These three agencies have taken steps to work more closely together including MOUs which included delineating responsibility. Three three agencies affect almost the entire population of the US and from a 'users' perspective, the potential overlapping jurisdiction would add greatly to the complexity of the regulations from these agencies. Fortunately, all three agencies try to work together, which benefits us all.