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Title:
METHOD OF REMOVING CHEMICAL STERILANT RESIDUES
Document Type and Number:
WIPO Patent Application WO/2020/174323
Kind Code:
A1
Abstract:
A method of removing residual ethylene oxide from an article exposed to ethylene oxide is provided. The method includes, after exposing the article to ethylene oxide in a sterilization chamber, reducing the concentration of ethylene oxide in the chamber to less than 30,000 ppm; while applying a first negative pressure in the chamber and maintaining a temperature in the chamber between 30-75º C, injecting a quantity of heated water or steam into the chamber; and, after injecting the heated water or steam into the chamber, applying a second negative pressure of less than or equal to 30 kPa in the chamber while maintaining the temperature in the chamber. The first negative pressure is between 10-90 kPa. The quantity of heated water or steam injected into the chamber maintains a relative humidity of at least 40% in the chamber for a period of time.

Inventors:
LYDEEN MARK D (US)
LIU HSI-CHOU (US)
TALAPA LAWRENCE M (US)
WITCHER KELVIN J (US)
NOMA YURI (JP)
Application Number:
PCT/IB2020/051397
Publication Date:
September 03, 2020
Filing Date:
February 19, 2020
Export Citation:
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Assignee:
3M INNOVATIVE PROPERTIES CO (US)
International Classes:
A61L2/20; A61L2/24
Domestic Patent References:
WO2013043429A12013-03-28
Foreign References:
US4822563A1989-04-18
Attorney, Agent or Firm:
ADAMSON, Trisha D., et al. (US)
Download PDF:
Claims:
What is claimed is:

1. A method of removing residual ethylene oxide from an article exposed to ethylene oxide in a sterilization chamber, the method comprising:

after exposing an article contained in the sterilization chamber to a concentration of ethylene oxide for a period of time, reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm;

while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber;

wherein the first negative pressure is between 10-90 kPa;

wherein the quantity of heated water or steam injected into the sterilization chamber is a quantity effective to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time; and after injecting the quantity of heated water or steam into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber.

2. A method of removing residual ethylene oxide from an article exposed to ethylene oxide, the method comprising:

while applying a first negative pressure in an aeration chamber and maintaining a temperature in the aeration chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber;

wherein, while applying the first negative pressure, the aeration chamber contains an article that was prior exposed to ethylene oxide during an ethylene oxide disinfection process or an ethylene oxide sterilization process;

wherein the first negative pressure is between 10-90 kPa;

wherein the quantity of heated water or steam injected into the aeration chamber is a quantity effective to maintain a relative humidity of at least 40% in the aeration chamber for a preselected period of time; and

after injecting the quantity of heated water or steam into the aeration chamber, applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber.

3. A method of sterilizing an article, the method comprising:

introducing water or steam into a sealed sterilization chamber to attain a relative humidity of about 20-90%, wherein the sealed sterilization chamber contains the article therein;

while maintaining the relative humidity and while maintaining a temperature of about 30-75° C in the sealed sterilization chamber, injecting ethylene oxide into the sterilization chamber;

after the injecting the ethylene oxide, exposing the article to the ethylene oxide for a period of time;

after the exposing the article to ethylene oxide for a period of time, reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm; while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the sterilization chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber;

wherein the first negative pressure is between 10-90 kPa;

wherein the quantity of heated water or steam injected into the sterilization chamber is sufficient to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time; and

after injecting the quantity of heated water into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber.

4. The method of any one of the preceding claims, further comprising, after the applying the second negative pressure, repeating the injecting the quantity of heated water or steam and the applying the second negative pressure at least once.

5. The method of claim 3 wherein, during the exposing the article to the ethylene oxide for a period of time, the sterilization chamber or aeration chamber has therein a preselected relative humidity and a preselected temperature.

6. The method of claim 5, wherein the preselected relative humidity is about 20-

90%.

7. The method of claim 5 or claim 6, wherein the preselected temperature is about 30-75° C.

8. The method of any one of the preceding claims, wherein the heated water is heated to about 85-100 0 C before it is injected into the sterilization chamber or aeration chamber.

9. The method of any one of the preceding claims, further comprising, while injecting the quantity of heated water into the sterilization chamber or aeration chamber, maintaining the first negative pressure at 60-90 kPa.

10. The method of any one of the preceding claims, wherein the quantity of heated water or steam injected into the sterilization chamber or aeration chamber is a quantity sufficient to maintain a relative humidity of at least 50% in the sterilization chamber or aeration chamber for the preselected period of time.

11. The method of any one of the preceding claims, wherein the quantity of heated water or steam injected into the sterilization chamber or aeration chamber is a quantity sufficient to maintain a relative humidity of at least 60% in the sterilization chamber or aeration chamber for the preselected period of time.

12. An automated ethylene oxide sterilizer comprising or operatively -coupled to a microprocessor that is configured to operate the sterilizer to execute the method of any one of claims 1 through 11.

13. An automated ethylene oxide sterilizer comprising or operatively -coupled to a plurality of microprocessors that are configured to operate the sterilizer to execute the method of any one of claims 1 through 11.

14. The automated sterilizer of claim 12 or claim 13, wherein the sterilization chamber is configured to receive ethylene oxide gas.

15. The automated sterilizer of any one of claims 12 through 14, wherein the sterilization chamber is configured to receive water or water vapor.

16. The automated sterilizer of any one of claims 12 through 15, wherein the sterilization chamber is adapted for temperature control inside the sterilization chamber.

17. The automated sterilizer of any one of claims 12 through 16, wherein the sterilization chamber is adapted for relative humidity control inside the sterilization chamber.

18. A non-transitory computer-readable medium storing a control program executable on an automated ethylene oxide sterilizer the program comprising instructions that cause a controller of the automated sterilizer to perform the steps of:

exposing an article contained in a sterilization chamber of the automated sterilizer to a concentration of ethylene oxide for a period of time;

reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm;

while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the sterilization chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber;

wherein the first negative pressure is between 10-90 kPa;

wherein the quantity of heated water or steam injected into the sterilization chamber is a quantity effective to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time; and after injecting the quantity of heated water or steam into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber.

19. A non-iransitory computer-readable medium storing a control program executable on an aeration chamber, die program comprising instructions that cause a controller of the automated sterilizer to perform the steps of:

while applying a first negative pressure in the aeration chamber and maintaining a temperature in the aeration chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber;

wherein the first negative pressure is between 10-90 kPa;

wherein the quantity of heated water or steam injected into the aeration chamber is a quantity effective to maintain a relative humidity of at least 40% in the aeration chamber for a preselected period of time; and

after injecting the quantity of heated water or steam into the aeration chamber, applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber.

Description:
METHOD OF REMOVING CHEMICAL STERILANT RESIDUES

Technical Field

[0001] The methods and articles of the present disclosure relate to the field of low-temperature sterilization technology.

Background

[0002] Ethylene oxide (ETO) is a gaseous sterilant that is used to sterilize materials and articles that are sensitive to high temperatures and/or high-moisture environments. For example, ethylene oxide sterilization processes are commonly used to sterilize medical devices and supplies in health care institutions in the United States. Automated sterilizers that use ethylene oxide gas as the sterilant are commercially available. Many of the sterilizers are pre-programmed to automatically execute all of the necessary steps of an ETO sterilization process.

[0003] Typical, ETO sterilization processes consist of five stages: 1) preconditioning and humidification, 2) introduction of ETO gas, 3) exposure, 4) evacuation, and 5) air washes. The first four stages routinely take up to about 2.5 hours. The aeration stage can last from about 4 hours up to about 7 days, depending upon the aeration temperature and the size and composition of the load that was sterilized. Negative pressure can be used during aeration to remove ETO residue from the sterilization chamber. The aeration stage is not considered complete until the quantity of ETO residue on the sterilized material is below a threshold that is considered safe by health care regulatory agencies.

[0004] A reduction of the time needed to complete ETO sterilization processes would be advantageous, especially when the articles to be sterilized are reusable.

Summary

[0005] The present disclosure provides methods of removing residual ethylene oxide from articles that have been exposed to an ethylene oxide sterilization or disinfection process. It is now known that heated water or steam can be injected into an ethylene oxide sterilization chamber during the aeration phase of the disinfection or sterilization cycle wherein the chamber is held at sub-atmospheric pressure and at a temperature that may permit condensation for a period of time of at least a portion of the heated water or steam onto an article in the chamber. Alternatively, the heated water or steam can be injected into an aeration chamber under similar conditions. These methods result in improved extraction of ethylene oxide and derivatives thereof from the articles. Advantageously, the methods can reduce the amount of time needed to reduce the amount of ethylene oxide and derivatives thereof from the articles.

[0006] In one aspect, the present disclosure provides a method of removing residual ethylene oxide from an article exposed to ethylene oxide in a sterilization chamber. The method can comprise: after exposing an article contained in the sterilization chamber to a concentration of ethylene oxide for a period of time, reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm; while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the sterilization chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber; and after injecting the quantity of heated water or steam into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber. The first negative pressure can be between 10-90 kPa. The quantity of heated water or steam injected into the sterilization chamber can be a quantity effective to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time.

[0007] In another aspect, the present disclosure provides a method of removing residual ethylene oxide from an article exposed to ethylene oxide. The method can comprise: while applying a first negative pressure in an aeration chamber and maintaining a temperature in the aeration chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber; and after injecting the quantity of heated water or steam into the aeration chamber, applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber. While applying the first negative pressure, the aeration chamber contains an article that was prior exposed to ethylene oxide during an ethylene oxide disinfection process or an ethylene oxide sterilization process. The first negative pressure can be between 10-90 kPa. The quantity of heated water or steam injected into the aeration chamber can be a quantity effective to maintain a relative humidity of at least 40% in the aeration chamber for a preselected period of time

[0008] In yet another aspect, the present disclosure provides a method of sterilizing an article, the method comprising: introducing water or steam into a sealed sterilization chamber to attain a relative humidity of about 20-90%, wherein the sealed sterilization chamber contains the article therein; while maintaining the relative humidity and while maintaining a temperature of about 30- 75° C in the sealed sterilization chamber, injecting ethylene oxide into the sterilization chamber; after injecting the ethylene oxide, exposing the article to the ethylene oxide for a period of time; after exposing the article to ethylene oxide for a period of time, reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm; while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the sterilization chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber; and after injecting the quantity of heated water into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber. The second negative pressure can be between 10-90 kPa. The quantity of heated water or steam injected into the sterilization chamber can be a quantity sufficient to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time. In any embodiment of the method of sterilizing the article, during the exposing the article to the ethylene oxide for a period of time, the sterilization chamber can have therein a preselected relative humidity and a preselected temperature.

[0009] In any of the above embodiments, the method further can comprise, after the applying the second negative pressure, repeating the injecting the quantity of heated water or steam and the applying the second negative pressure at least once. In any of the above embodiments of the method, the heated water can be heated to about 85-100 0 C before it is injected into the sterilization chamber or aeration chamber. In any of the above embodiments, the method further can comprise, while injecting the quantity of heated water into the sterilization chamber or aeration chamber, maintaining the second negative pressure at 60-90 kPa.

[0010] In yet another aspect, the present disclosure provides an automated ethylene oxide sterilizer. The automated ethylene oxide sterilizer can comprise or can be operatively-coupled to a microprocessor that is programmed to operate the sterilizer to execute any one of the above embodiments of the method.

[0011] In yet another aspect, the present disclosure provides an automated ethylene oxide sterilizer. The automated ethylene oxide sterilizer can comprise or can be operatively-coupled to a plurality of microprocessors that are programmed to operate the sterilizer to execute any one of the above embodiments of the method.

[0012] In any of the above embodiments of the automated sterilizer, the sterilization chamber can be configured to receive ethylene oxide gas. In any of the above embodiments of the automated sterilizer, the sterilization chamber can be configured to receive water or water vapor.

In any of the above embodiments of the automated sterilizer, the sterilization chamber can be adapted for temperature control inside the chamber. In any of the above embodiments of the automated sterilizer, the sterilization chamber is adapted for relative humidity control inside the sterilization chamber.

[0013] In yet another aspect, the present disclosure provides a non-transitory computer-readable medium storing a control program executable on an automated ethylene oxide sterilizer. The program can comprise instructions that cause a controller of the automated sterilizer to perform tire steps of: exposing an article contained in a sterilization chamber of the automated sterilizer to a concentration of ethylene oxide for a period of time; reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm; while applying a first negative pressure in the sterilization chamber and maintaining a temperature in the sterilization chamber between 30-75° C, injecting a quantity of heated water or steam into the sterilization chamber; and after injecting the quantity of heated water or steam into the sterilization chamber, applying a second negative pressure of less than or equal to 30 kPa in the sterilization chamber while maintaining the temperature in the sterilization chamber. The first negative pressure can be between 10-90 kPa. The quantity of heated water or steam injected into the sterilization chamber can be a quantity effective to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time.

[0014] In yet another aspect, the present disclosure provides a non-transitory computer-readable medium storing a control program executable on an aeration chamber. The program can comprise instructions that cause a controller of tine aeration chamber to perform the steps of: while applying a first negative pressure in the aeration chamber and maintaining a temperature in the aeration chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber; and after injecting the quantity of heated water or steam into the aeration chamber, applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber. The first negative pressure can be between 10-90 kPa. The quantity of heated water or steam injected into the aeration chamber can be a quantity effective to maintain a relative humidity of at least 40% in the aeration chamber for a preselected period of time.

[0015] Additional details of these and other embodiments are set forth in the accompanying drawings and the description below. Other features, objects and advantages will become apparent from the description and drawings, and from the accompanying claims.

[0016] “Cycle”, as used herein, is a term used in the art of automated disinfection and sterilization and refers to the complete process (e.g., multi-phase process) of disinfecting or sterilizing an article in an automated sterilizer or automated disinfector. Typically, the cycle begins when the automated sterilizer or disinfector is actuated to execute the process and the cycle ends when the automated sterilizer or disinfector completes the last automated phase (e.g., aeration) of the process.

[0017] “ETO” and“EO”, as used herein, are both abbreviations for the term“ethylene oxide”.

[0018] The term "comprising" and variations thereof (e.g., comprises, includes, etc.) do not have a limiting meaning where these terms appear in the description and claims.

[0019] As used herein, "a", "an", "the," "at least one, "and "one or more" are used

interchangeably, unless the context clearly dictates otherwise. [0020] Also herein, the recitations of numerical ranges by endpoints include all numbers subsumed within that range (e.g., 500 to 7000 nm includes 500, 530, 551, 575, 583, 592, 600, 620, 650, 700, etc.).

[0021] The above summary is not intended to describe each disclosed embodiment or every implementation of the invention. The description that follows more particularly exemplifies illustrative embodiments.

Brief Description of Drawings

[0022] FIG. 1 is a block diagram of one embodiment of a prior art method of sterilizing an article using ethylene oxide.

[0023] FIG. 2 is a graph of the temperature and pressure within the sterilization compartment of an automated sterilizer during the automated execution of the prior art method of sterilizing an article of FIG 1.

[0024] FIG. 3 is a block diagram of one embodiment of a method of removing residual ethylene oxide from an article exposed to ethylene oxide in a sterilization chamber according to the present disclosure.

[0025] FIG. 4 is a block diagram of an alternative embodiment of a method of removing residual ethylene oxide from an article exposed to ethylene oxide according to the present disclosure.

[0026] FIG. 5 is a graph of the temperature and pressure within the sterilization compartment of an automated sterilizer during the automated execution of one embodiment of a method of sterilizing an article according to the present disclosure.

Detailed Description

[0027] Every year, millions of surgical procedures are performed world-wide. During each of these procedures, a surgical instrument and/or a medical device contacts or breaches a patient’s skin or mucous membrane. Many of the instruments and devices are reusable. Thus, in order to render the instrument or device safe to use on another patient, it must be cleaned to remove body tissue and/or fluids and either disinfected or sterilized to inactivate human pathogens present on and/or in the instrument or device. The choice of cleaning/disinfection/sterilization procedure for any given instrument or device is often dictated by the object’s resistance to degradation by moisture, heat, and/or chemicals.

[0028] Low-temperature disinfection/sterilization methods are particularly useful for reusable instruments that are sensitive to degradation by heat or steam. Examples of sterilants used in low- temperature disinfection or sterilization procedures include, but are not limited to, ethylene oxide gas (“ETO”), hydrogen peroxide, peracetic acid, and ozone. When using these sterilants, the disinfection/sterilization procedures generally include measures to reduce the amount of residual sterilant remaining on the instrument or medical device to a quantity that is generally considered safe to the patient in which the instrument or medical device subsequently will be used.

[0029] The United States Department of Health and Human Services Centers for Disease Control and Prevention, for example, publish guidelines for disinfection and sterilization in healthcare facilities (“Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008”, hereinafter,“CDC Guideline”); W.A. Rutala et al., eds.; available at

https://www.cdc.gov/infectioncontrol/guidelines/disinfect ion/; which is incorporated herein by reference in its entirety). The CDC Guideline describes on page 62 a typical method for ethylene oxide sterilization. This prior art method 100 is shown in FIG. 1.

[0030] The method 100 is typically conducted in an automated sterilizer that comprises a sterilization chamber into which the articles to be disinfected or sterilized are placed. Automated ethylene oxide sterilizers are commercially available. An example of an automated ethylene oxide sterilizer is a Steri-Vac GS8 sterilizer available from 3M Company (St. Paul, MN).

[0031] Referring back to FIG. 1, the method 100 includes a step 110 of preconditioning and humidifying the contents of the sterilization chamber. The intent of preconditioning the articles to be sterilized is to bring the temperature and relative humidity of the articles to a stable internal temperature and moisture content that will facilitate the microbicidal effects of the ethylene oxide sterilant. In some embodiments, the step 110 can be conducted in the sterilization chamber.

Alternatively, or additionally, this step can be conducted in an environmental chamber that is separate from the automated sterilizer and the preconditioned articles can be transferred to the sterilization chamber for sterilization.

[0032] After preconditioning the articles to be disinfected or sterilized, the method 100 includes the step 112 of introducing the ethylene oxide into the sterilization chamber. Prior to introducing the ethylene oxide into the sterilization chamber, the method typically includes a step (not shown) of removing the air from the sterilization chamber by applying a vacuum into the sterilization chamber or by applying a series of vacuums, followed by air flushes. These procedures render it safer to introduce the ethylene oxide into the sterilization chamber.

[0033] After introducing the ethylene oxide into the sterilization chamber, the method 100 includes the step 114 of exposing the article(s) to be sterilized to the ethylene oxide in the sterilization chamber for a period of time. Typically, the period of time is a predetermined period of time. The predetermined period of time may be selected by, inter alia, i) the size and composition of the article(s) to be disinfected or sterilized, ii) the estimated quantity of contamination (“soil”) present on the article(s), iii) the desired extent of disinfection or sterilization, and iv) the concentration of ethylene oxide in the sterilant gas. [0034] After exposing the article(s) to be disinfected or sterilized to the ethylene oxide, the method 100 includes the step 116 of evacuating the sterilization chamber. This step removes substantially all of the gaseous ethylene oxide from the sterilization chamber. However, typically, some ethylene oxide and toxic ethylene oxide derivatives may remain associated with the inside of the sterilization chamber and the articles therein. Thus, the method 100 further includes the step 118 of“air washes” to facilitate the removal of most of the residual ethylene oxide and toxic derivatives thereof from the sterilization chamber and the articles therein.

[0035] Air washes typically consist of alternately pulling a vacuum in the sterilization chamber and at least partially releasing the vacuum by substantially backfilling the sterilization chamber with a non-combustible gas (e.g., air or nitrogen). Optionally, the sterilization chamber can be heated during the air washes to help flash off the ethylene oxide residue. As an alternative to air washes in the sterilization chamber, the contents of the sterilization chamber can be removed to an aeration chamber (e.g., a heated chamber or room) for a period of time sufficient to reduce the residual ethylene oxide and toxic derivatives thereof to safe levels. The aeration chamber is continuously out-gassed to reduce the in-product residues.

[0036] FIG. 2 shows a graph of the temperature and pressure within the sterilization compartment of an automated sterilizer during the automated execution of the prior art method of sterilizing an article discussed in the CDC Guidelines. The graph shows that during the preconditioning phase (designated“I” in FIG. 2), the temperature is raised from ambient to about 55 degrees C (see line 44) and the pressure is reduced from ambient to about 16 kPa (see line 42). The brief injection phase (designated“II” in FIG. 2), when ethylene oxide gas is injected into the sterilization chamber, is initiated while the relative humidity is maintained and the vacuum in the chamber is relatively deep (e.g., about 16 kPa). FIG. 2 shows that the pressure in the sterilization chamber rises (e.g., to about 65 kPa) as the EO is injected. In this embodiment, a negative pressure of about 65 kPa is held during the exposure phase (designated“HI” in FIG. 2). After the exposure phase, the ethylene oxide is substantially removed from the sterilization chamber during a vacuum phase (designated“IV” in FIG. 2). In the air wash phase (designated“V” in FIG. 2), a series of vacuums, followed by ingresses of nitrogen (causing a decrease in the vacuum in the chamber) complete the sterilization cycle. After the air washes, the vacuum in the sterilization chamber is released and the contents of the chamber can be removed.

[0037] The CDC Guideline acknowledges that a typical basic ETO sterilization cycle takes approximately 2.5 hours excluding aeration time. Mechanical aeration at an elevated temperature (50 to 60°) can take 8 to 12 hours to desorb toxic ETO residuals from exposed absorbent materials. The desorption process can alternatively be performed at room temperature. However, when the desorption is conducted at 20° C, the aeration process requires 7 days. [0038] The disclosed method significantly reduces the time needed to reduce the toxic ETO residuals in articles that have been exposed to an ETO disinfection or sterilization process.

Moreover, the method can be performed in automated sterilizers and thereby potentially obviate the need for a separate aeration chamber or room.

[0039] In one aspect, the method removes residual ethylene oxide from an article exposed to ethylene oxide in a sterilization chamber. FIG. 3 shows one embodiment of the method according to the present disclosure. The method 200 comprises the step 222 of reducing the concentration of ethylene oxide in the sterilization chamber to less than 30,000 ppm while the sterilization chamber contains an article that was prior exposed to ETO (e.g., during a disinfection or sterilization process). The concentration of ethylene oxide in the sterilization chamber is reduced to less than 30,000 ppm, for example, to reduce the quantity of ETO in the sterilization chamber to a concentration at least below the limit of flammability for ETO. The reducing step can be accomplished by pulling a vacuum between about 10-20 kPa. Other suitable vacuums used to reduce the concentration of ETO in the sterilization chamber can be less than 10 kPa, providing the article to be disinfected or sterilized is stable to selected vacuum pressure.

[0040] While applying a first negative pressure in the sterilization chamber, the method 200 further includes the step 222 of injecting a quantity of heated water or steam into the sterilization chamber. While the first negative pressure is applied, the temperature in the sterilization chamber preferably is maintained between 30-75° C. The first negative pressure is between 10-90 kPa. The quantity of heated water or steam injected into the sterilization chamber is a quantity effective to maintain a relative humidity of at least 40% in the sterilization chamber for a preselected period of time.

[0041] After injecting the heated water or steam into the sterilization chamber, the method 200 includes the step 224 of applying a second negative pressure in the sterilization chamber while maintaining the temperature in the sterilization chamber. The second negative pressure preferably is less than or equal to 30 kPa. The second negative pressure facilitates removal of ETO residuals and the injected water or steam from the sterilization chamber and from the article(s) contained therein.

[0042] In any embodiment (not shown), the method of removing residual ethylene oxide from an article exposed to ethylene oxide in a sterilization chamber further includes, after the applying the second negative pressure, repeating at least once the injecting the quantity of heated water or steam followed by the applying the second negative pressure. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least two times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least three times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least four times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to five times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to six times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to eight times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to ten times or more.

[0043] In some embodiments, the aforementioned method 200 can be used as an aeration subprocess of an overall sterilization process (that includes preconditioning and/or exposing to ethylene oxide an article to be sterilized) conducted in an automated sterilizer. FIG. 5 shows a graph of the temperature and pressure within the sterilization compartment of an automated sterilizer during the automated execution of one embodiment of the method of sterilizing an article with ethylene oxide according to the present disclosure.

[0044] In some embodiments, a method according to the present disclosure can be used as a discreet process (e.g., in an aeration chamber) after the sterilized article(s) are removed from an automated sterilizer. The method reduces the quantity of ETO residuals on articles that have been subjected to an ethylene oxide sterilization process, as shown in the Examples hereinbelow.

Because the method is more efficient at removing ETO residuals than the traditional air washes, the method can shorten the time needed to reduce the ETO residuals associated with articles that are subjected to ETO sterilization processes. Advantageously, the method can be used to optimize re-use of a particular reusable surgical instrument or medical device.

[0045] FIG. 4 shows one embodiment of a method 300 of removing residual ethylene oxide from an article exposed to ethylene oxide. The method 300 comprises the step 330 of, while applying a first negative pressure in an aeration chamber and maintaining a temperature in the aeration chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber. The first negative pressure is between 10-90 kPa. While applying the first negative pressure, the aeration chamber contains an article that was prior exposed to ethylene oxide during an ethylene oxide disinfection process or an ethylene oxide sterilization process.

[0046] In some embodiments, the article is exposed to ethylene oxide during an ethylene oxide disinfection process or an ethylene oxide sterilization process for at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 30 minutes, at least about 45 minutes, at least about 60 minutes, at least about 90 minutes, or at least about 120 minutes prior to applying the first negative pressure. In some embodiments, the article was exposed to ethylene oxide during an ethylene oxide disinfection process or an ethylene oxide sterilization process not more than 15 minutes, not more than 30 minutes, not more than 60 minutes, not more than 90 minutes, not more than 2 hours, not more than 4 hours, not more than 6 hours, not more than 8 hours, not more than 12 hours, or not more than 24 hours prior to applying the first negative pressure.

[0047] Referring back to FIG. 4, the method 300 comprises the step 332 of applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber.

[0048] In any embodiment (not shown), the method of removing residual ethylene oxide from an article exposed to ethylene oxide further includes, after the applying the second negative pressure, repeating at least once the injecting the quantity of heated water or steam followed by the applying the second negative pressure. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least two times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least three times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated at least four times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to five times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to six times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to eight times. In some embodiments, the injecting the quantity of heated water or steam followed by the applying the second negative pressure is repeated up to ten times or more.

[0049] Without being bound by theory, the Applicants believe the methods described herein facilitate removal of ETO residuals from the chamber and the contents therein because the heated water or steam is injected into the sterilization chamber wherein the ambient temperature and pressure conditions are conducive to condensation of the water or steam on the articles in the sterilization chamber (i.e., at the prescribed first negative pressure, the temperature in the sterilization chamber and the contents therein is below the boiling point of the injected water or steam). Thus, the injected water or steam can condense onto the surface of articles in the sterilization chamber, thereby rinsing and/or dissolving the residuals. When the second negative pressure is applied to the sterilization chamber, the ETO residuals are extracted from the surface and flashed off with the water as the boiling point of water drops in the sterilization chamber.

These and other potential mechanisms result in more efficient removal of ETO residuals than air washes or other procedures (e.g., deeper vacuum) that otherwise would preclude condensation of water vapor in the sterilization chamber. [0050] In any method, the method includes injecting a quantity of heated water or steam into a sterilization chamber or an aeration chamber. When heated water is used, the water is heated preferably to about 85-100° C before it is injected into the chamber. In some embodiments, the water is heated preferably to about 90-100° C before it is injected into the chamber. In some embodiments, the water is heated preferably to about 95-100° C before it is injected into the chamber. In some embodiments, the water is heated preferably to about 99° C before it is injected into the chamber. Without being bound by theory, it is believed that the use of heated water favors rapid conversion of the water to steam in the negative-pressure environment in the sterilization chamber or aeration chamber. After it is converted to steam, the steam can quickly condense into water on the surface of objects contained in the chamber.

[0051] The quantity of heated water or steam injected into the sterilization chamber or aeration chamber is sufficient to maintain a relative humidity of at least 40% in the chamber for a preselected period of time. In certain embodiments, the quantity of heated water or steam injected into the sterilization chamber or aeration chamber is sufficient to maintain a relative humidity of at least 50% in the chamber for a preselected period of time. In certain embodiments, the quantity of heated water or steam injected into the sterilization chamber or aeration chamber is sufficient to maintain a relative humidity of at least 60% in the chamber for a preselected period of time. A person having ordinary skill in the art will recognize that the quantity of heated water or steam needed to maintain a preselected humidity for a period of time will depend upon certain factors (e.g., the volume of the chamber).

[0052] Maintaining a preselected relative humidity for a preselected period of time comprises maintaining the humidity for a period sufficient to extract at least a portion of the ETO residuals from the contents of the sterilization chamber or aeration chamber. A person having ordinary skill in the art will recognize a sufficient period of time will depend upon certain factors (e.g., the size and complexity (e.g., surface area, devices or instruments with one or more lumens). In any embodiment of the methods of the present disclosure, the preselected time is less than 2 minutes; in certain embodiments, not less than 2 minutes; in certain embodiments, not less than 3 minutes; in certain embodiments, not less than 5 minutes; in certain embodiments, not less than 10 minutes; in certain embodiments, not less than 15 minutes; in certain embodiments, not less than 20 minutes; or, in certain embodiments, not less than 30 minutes. In any embodiment of the present disclosure, the preselected time is up 5 minutes, up to 10 minutes, up to 30 minutes, up to 40 minutes, up to 50 minutes, up to 60 minutes, up to 90 minutes, up to 120 minutes or, in some instances, longer.

[0053] Method of ethylene oxide disinfection or sterilization are typically executed in an automated ethylene oxide sterilizer, which are commercially available as discussed above. The automated sterilizers typically are equipped with, or operably connected to, a sealable sterilization chamber, a source of negative pressure, a source of ethylene oxide, a source of water and/or steam, a heat source, a source of air (e.g., a controllable valve to permit selective ingress of ambient air) and/or nitrogen, valves to control the flow of fluids (e.g., gasses and/or liquids) into and out of the sterilization chamber, sensors (e.g., temperature, pressure, humidity), microprocessors and/or controllers (e.g., controlling temperature, pressure, humidity, and/or concentration of ethylene oxide in the sterilization chamber by actuating or deactivating the appropriate components (e.g., valves, heat-exchangers, timers) of the sterilizer), and at least one non-transitory computer- readable medium storing a control program executable on the automated ethylene oxide sterilizer.

[0054] Embodiments of the methods of the present disclosure are well suited to be executed in an automated ethylene oxide sterilizer. Many commercial sterilizers are pre-programmed to execute methods of ethylene oxide sterilization using prescribed parameters of preconditioning, exposure to ethylene oxide, and/or aeration. In some instances, the automated sterilizers are configured so that certain of the parameters may be modified by the operator. Methods of programming an automated sterilizer to execute sterilization methods are well known to a person having ordinary skill in the appropriate art. Thus, in another aspect, the present disclosure provides an automated ethylene oxide sterilizer comprising or operatively-coupled to a microprocessor that is configured (e.g., programmed) to operate the sterilizer to execute an embodiment of the methods described.

[0055] In some instances, a plurality of microprocessors may be programmed to act cooperatively to execute an embodiment of a method of ethylene oxide sterilization. Thus, in yet another aspect, the present disclosure provides an automated ethylene oxide sterilizer comprising or operatively-coupled to a plurality of microprocessors that are configured (e.g., programmed) to act cooperatively to operate the sterilizer to execute an embodiment of the methods disclosed.

[0056] Non-transitory computer-readable media can be used to store a program directing an automated sterilizer to execute an embodiment of the methods disclosed. Thus, in yet another aspect, the present disclosure provides a non-transitory computer-readable medium storing a control program executable on an aeration chamber, the program comprising instructions that cause a controller of the automated sterilizer to perform the steps of: i) while applying a first negative pressure in the aeration chamber and maintaining a temperature in the chamber between 30-75° C, injecting a quantity of heated water or steam into the aeration chamber; wherein the first negative pressure is between 10-90 kPa; wherein the quantity of heated water or steam injected into the aeration chamber is a quantity effective to maintain a relative humidity of at least 40% in the aeration chamber for a preselected period of time; and ii) after injecting the quantity of heated water or steam into the aeration chamber, applying a second negative pressure of less than or equal to 30 kPa in the aeration chamber while maintaining the temperature in the aeration chamber.

[0057] The basic elements of the methods of the present disclosure can be applied to other low- temperature sterilization processes (e.g., those using hydrogen peroxide, peracetic acid, and/or ozone as the sterilant) to achieve a similar outcome (i.e., improved removal of sterilant residue and/or sterilant-derived residues).

Examples

[0058] Detection of ETO residuals on Endoscopes

[0059] Olympus ® TJF-180V video duodenoscopes were exposed to ethylene oxide sterilization processes as described below. After the scopes were removed from the ethylene oxide sterilizers, they were processed as described hereinbelow to quantify the amount of water-extractable ETO residuals remained on scopes.

[0060] After the sterilization process, including the aeration step, the scopes were retrieved immediately from the sterilization chamber and the ETO residuals were extracted as described below.

[0061] Extractions were performed using at least 2.1 L purified water (“extraction solvent”) containing glass beads (approximately 3.6 kg of 6mm diameter soda lime glass beads). The water and beads were pre-warmed to 37°C ± 2 c for a minimum of 2 hours

[0062] Fill Connector Assembly

[0063] A fill connector assembly was used to facilitate transfer of the extraction solvent into the various channels of the duodenoscopes. The assembly was made as follows: A 5-milliliier plastic syringe was cut at approximately the 2 -ml mark. Rubber tubing having an inner diameter of 6.4 mm was cut to a length of approximately 5 cm. Polypropylene tubing having an outer diameter of 6.4 m was cut to a length of approximately 19 mm. Tire w ide end of the cut 5 ml syringe was inserted approximately 13 cm into the rubber tubing such that the Luer-Lok™ portion of the cut syringe was exposed lire polypropylene tube section wars press-fitted onto the Luer-Lok™ portion of the cut syringe.

[0064] Filling the Endoscope inner channels

[0065] During the filling procedure, one person filled the channels of endoscope, one person held the Control section of the endoscope, and one person held the endoscope connector. The endoscope was filled with the control portion elevated above the distal end and the connector was elevated above the control portion. The endoscope was filled slowly to minimize any loss of extraction solvent from one or more of the inner channels prior to plugging each port or connector during the fill process described below. [0066] The suction Cylinder and the air/water cylinder were opened. The robber end of the fill connector assembly was slipped over the distal end of the endoscope. A 60-mL syringe was filled with the pre-warmed extraction solvent and the tip of the 60-mL syringe was inserted into the polypropylene tubing of the fill connector assembly. Pre-warmed extraction solvent was slowly pushed into the endoscope from the 60-ml syringe via the fill connector assembly. When extraction solvent was observed beginning to emerge from the instrument channel port (located on the control section of the endoscope) the fill ing process was discontinued and the instrument channel port was plugged using the biopsy valve cap or an appropriately-sized stopper. The filling process was resumed until the extraction solvent is observed emerging from the suction connector, the air supply connector and the water supply connector located in the endoscope connector portion. The filling was discontinued, and the air supply connector and the water supply connector were sealed with their respective covers. The suction connector was wrapped with Parafilm M paraffin film (Bemis NA; Neenab, WT).

[0067] After the suction, air supply and water supply connectors w ere plugged, the filling resumed until water is observed emerging from the air pipe at the top of the endoscope connector portion. The air pipe was sealed with its respective cover or an appropriately-sized robber stopper. The fill connector assembly was detached and the opening at the distal end of the endoscope was plugged using an appropriately-sized rubber stopper. The volume used to fill the inner channel of the device (approximately 50 ml) was recorded.

[0068] Placement of the endoscope into an extraction vessel

[0069] Tire insertion tube of each endoscope was inserted into a 2800 ml Fembach flask so that it coiled upon itself as it went into the flask. After the insertion tube was properly placed into the flask, the control section of the scope was disposed in the neck of the flask The universal tube remained outside the flask during the extraction.

[0070] The pie-weighed and pre-warmed glass beads were added to the flask, followed by 1000 ml of the prewarmed extraction solvent. The control section of the device was positioned so that the extraction solvent was above the insertion tube limit mark on tire insertion tube but below as much of the device boot as possible. The opening of the flask and the portion of the endoscope di sposed in the neck of the flask were wrapped with several layers of Parafilm M film to seal the flask and immobilize the control section of the scope

[0071] Extraction and Recovery

[0072] The Fembach flasks; with the devices, glass beads, and extraction solvent therein; were incubated at 37°C ± 2° C . The flasks were agitated on a rotary shaker at approximately 50 rpm during the incubation period. The Fembach flasks were removed from the incubator after 2 hours i 5 minutes. The extraction solvent was poured from the Fembach flask containing the endoscope into a suitable beaker and immediately transferred to an 11 -dram vial (leaving little headspace) and sealed with a PTFE-lined cap

[0073] The endoscope was carefully removed from the Fembaeh flask and residual liquid was wiped from the exterior of the scope The contents of the inner scope were drained from the distal end of the scope into an appropriately-sized dram vial and capped wit a PTFE-lined cap

[0074] The recovered extracts were allowed to cool to room temperature. Once cooled, a portion of each extract was transferred to a separate autosampler vial for analysis by gas chromatography-mass spectrometry (GC-MS).

[0075] The total residual ethylene oxide (EO) and ethylene chlorohydrin (ECH), in mg/device, extracted from each device was calculated as shown:

mg/device = gg/m L c 1 mg/lOOOpg c EV/device

Where:

EV is the extraction volume (mL) for the outer or inner extraction.

The total residual EO and ECH concentrations were determined by summing the results for the inner and outer endoscope extracts as shown :

Total EO pg/device = EO A + EO B

Total ECH pg/device = ECH A + ECH B

Where:

A ::: pg/device for the endoscope inner channel extract

B = pg/device for the external endoscope extract

[0076] Negative Control

[0077] A negative control, consisting of 3.6 kg of the pre-warmed glass beads shaken in a Fembaeh flask with 1000 mL of pre warmed extraction solvent was analyzed similar to the extracts form the endoscopes.

[0078] Automated Ethylene Oxide Sterilizer

[0079] All experiments were conducted using a 3M™ Steri-Vac™ Model GS8

Sterilizer/Aerator. The 55° C cycle is one of the pre-programmed sterilization protocols that is included with the GS8 sterilizer. The relevant parameters for each respective sterilization cycle used in the Examples are listed in Table 1. The unique parameters listed in Table 1 were programmed into the sterilizer by writing and installing files (defining the unique parameters) that were read by a microprocessor in the automated sterilizer which used the parameters set forth in the files to modify the respective cycles.

[0080] Table 1. Parameters for each of the cycles run in the EO sterilizer for Reference Examples 1 and 2 and for Example 1.

1 - Number of minutes that the pressure in the chamber is held between about 58 kPa and about 80 kPa in each purge pulse. During the Purge Dwell, the vacuum pump was operating at maximum capacity and the vent to the sterilization chamber was open.

2 - These parameters are standard for the 55° C cycle of the Model GS8 Sterilizer.

3 - N/A = Not Applicable.

4 - The heated water was injected for 800 msec every 15 seconds during the 37-minute Purge Dwell. The target Relative Humidity for the water injection period was about 60%. The actual RH during the purge pulses was verified using a data tracer in the sterilization chamber during an otherwise identical cycle that did not include injection of ethylene oxide into the chamber.

[0081] Reference Example 1.

[0082] An Olympus ® TJF-180V video duodenoscope was packaged in two layers of polypropylene nonwoven wraps (Part No. KC400; Kimberly-Clark Corporation; Irving, TX). The wrapped scope was placed into the sterilization chamber of a 3M Steri-Vac Model GS8

Sterilizer/Aerator and was processed in the sterilizer using the 55° C standard cycle that is preprogrammed into the GS8 Sterilizer/Aerator. Key process parameters for the program are shown in Table 1. A graph of the temperature and pressure inside the sterilization chamber during this ethylene oxide sterilization process is shown in FIG. 2. At the completion of the sterilization process, the ETO residuals on and inside the scope were extracted and analyzed as described hereinabove.

[0083] Reference Example 2.

[0084] An Olympus ® TJF-180V video duodenoscope was packaged in two layers of polypropylene nonwoven wraps (Part No. KC400; Kimberly-Clark Corporation; Irving, TX). The wrapped scope was placed into the sterilization chamber of a 3M Steri-Vac Model GS8 Sterilizer/Aerator and was processed in the sterilizer using a first modification of the 55° C standard cycle that is preprogrammed into the GS8 Sterilizer/Aerator. Key process parameters for the modified program are shown in Table 1. At the completion of the sterilization process, the ETO residuals on and inside the scope were extracted and analyzed as described hereinabove.

[0085] Example 1.

[0086] An Olympus ® TJF-180V video duodenoscope was packaged in two layers of polypropylene nonwoven wraps (Part No. KC400; Kimberly-Clark Corporation; Irving, TX). The wrapped scope was placed into the sterilization chamber of a 3M Steri-Vac Model GS8

Sterilizer/Aerator and was processed in the sterilizer using a second modification of the 55° C standard cycle that is preprogrammed into the GS8 Sterilizer/Aerator. Key process parameters for the modified program are shown in Table 1. A graph of the temperature and pressure inside the sterilization chamber during this ethylene oxide sterilization process is shown in FIG. 5. At the completion of the sterilization process, the ETO residuals on and inside the scope were extracted and analyzed as described hereinabove.

[0087] Results

[0088] Table 2 shows the quantity of ethylene oxide extracted from the endoscopes used in the sterilization processes of Reference Example 1, Reference Example 2, and Example 1, respectively. The results indicate that, even though the endoscopes were aerated for the same period of time in each respective process, the aeration process of Example 1 removed almost twice as much ethylene oxide residue from the endoscopes. Moreover, the aeration process of Example 1 removed approximately three times as much ethylene oxide residue from the internal surfaces of the scopes. The quantity of ethylene chlorohydrin and ethylene glycol in all of the water extracts was either below the limit of detection of the analytical methods used or was far below the safety limits set by the U.S. guidelines.

[0089] Table 2. Ethylene oxide residue extracted from endoscopes after ETO sterilization processes. All values in the table represent the number of micrograms of ETO extracted from the respective portions of the endoscopes.

[0090] The complete disclosures of the patents, patent documents, and publications cited herein are incorporated by reference in their entirety as if each were individually incorporated. [0091] Various modifications and alterations to this invention will become apparent to those skilled in the art without departing from the scope and spirit of this invention. It should be understood that this invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein and that such examples and embodiments are presented by way of example only with the scope of the invention intended to be limited only by the claims set forth herein.