Inactivation of Beta-Lactams

Beta-lactam antibiotics are, by definition, a class of antibiotics which contain a beta-lactam ring in their structure. They are split into various groups depending upon their base structure, with the main groups being penicillins, carbapenems, cephalosporins, and monobactams. Allergic reactions to beta-lactams can be life-threatening. Due to the large number of individuals allergic, the pharmaceutical industry explored a method for their inactivation.   This research was performed such that a contaminated area could be treated and re-used for the future production of non-beta-lactam compounds. This would allow companies to “recycle” beta-lactam facilities instead of demolishing them upon the completion of production.

Testing was conducted using chlorine dioxide gas at various concentrations and exposure times in an effort to achieve the pharmaceutical manufacturer’s required 3-log (99.9%) reduction of eight different beta-lactams on various surfaces. Nine inactivation cycles were tested, with five passing the acceptance criteria beneath U.S. Food and Drug Administration (FDA)-required 0.03 ppm residue detection level. Successful inactivation cycles which achieved a 3-log reduction of all eight beta-lactam compounds all had cumulative exposures of over 7,240 ppm-hours. Further studies validated this dosage for providing a 3-log reduction of all eight beta-lactams tested.

In 2008, a leading pharmaceutical company was looking to renovate a 33-room facility, that had been used for the production of an Imipenem-based product, into a new training facility. Because positive samples for beta-lactams were found in multiple rooms and inside the ductwork, the entire production facility along with its HVAC was to be treated. Chlorine dioxide gas was injected into 24 locations and sampled from 12 locations to ensure fast and thorough distribution.  To ensure that gas was getting into the HVAC system, the recirculation blower was bumped throughout the process. Upon completion, the area was swabbed by the pharmaceutical company. All swabs came back negative proving that no beta-lactams remained, making the treatment a success.  Since that initial facility treatment in 2008, chlorine dioxide gas has been used for this specific application at a number of other facilities worldwide.

To learn more, click here.

How Does Chlorine Dioxide React with Water?

In most cases, before a decontamination occurs, the environment undergoes a wet cleaning to remove dirt and organic material.  This residual water can present a challenge for some decontamination methods.  One example being Vapor Phase Hydrogen Peroxide (VPHP) because it dilutes and breaks down in water.  So for that method to be effective, the area must be completely dry before use.  Depending on the application, drying the environment can be a lengthy process which adds a prohibitive amount of time to the cycle.

Chlorine dioxide (CD) gas is water soluble, allowing it to maintain its sterilization efficacy within water.  Unlike chlorine, CD gas does not form hydrochloric acid and maintains a neutral pH. In wet environments, chlorine dioxide can decontaminate any remaining water as well as the surfaces beneath.  This eliminates the need to wait until the environment is completely dry before decontamination occurs, in turn, decreasing the overall downtime.

One application where this has a real world effect is within decontamination chambers.  The use of decontamination chambers is becoming more prevalent within research facilities and clean rooms.  Within vivaria where space is extremely valuable, these chambers are sometimes included as part of a dual-use rack washer/decontamination chamber unit.  Within this application, if the system is run as a rack washer, the amount of water at the bottom of the chamber afterwards can take hours to completely dry out.  Being CD gas is not affected by water, it can be used within a dual-use chamber immediately after a wash cycle.  This can save your facility hours of time and allow the savings in facility footprint to become a viable option.  It also allows a contaminated facility the ability to become completely decontaminated as there’s no worry for residual water rendering the process ineffective.

Amplicon Inactivation

The rapid growth of DNA sequencing in laboratories is resulting in the increased use of PCR readers.  As a result,  researchers are making advances in science and medicine, but not without new challenges. One challenge is that the integrity of the results can be affected if amplicon residues contaminate part of the PCR reader. This contamination could cause improper analysis of subsequent samples. Mitigation of this problem requires amplicons to be inactivated from all surfaces of the PCR reader, including all cracks and crevices of the equipment.

Chlorine dioxide gas cycles have been validated with multiple PCR reader manufacturers in order to clear the reader from residual amplicons which can cause inaccurate results and readings.  The validation consisted of a series of cycles with varying chlorine dioxide gas dosages that were tested to achieve an inactivation of the amplicons. The verification process also confirmed that the equipment was not corroded as a result of the treatment cycles.

ClorDiSys Solutions, Inc performs amplicon inactivation work as part of its contract sterilization and decontamination services.  Two manufacturers of PCR readers have their customers send equipment to our facility before having it returned to the manufacturer for maintenance and repair.  At our facility, our contract sterilization team treats the units to eliminate any residual amplicons and blood-borne pathogens. This treatment allows the equipment to be safely handled by the manufacturers' maintenance department.

For more information, please read our Application Note on Amplicon Inactivation here.

Case Study: The Musculoskeletal Transplant Foundation (MTF) Isolator

The Musculoskeletal Transplant Foundation (MTF) is the nation’s leading tissue bank. MTF designed and validated the use of isolators in the production of DBX Demineralized Bone Matrix (DBX) putty. DBX Putty is the combination of demineralized bone and sodium hyaluronate for use during surgical application. Since the DBX putty is introduced into the body, it must be produced and packaged under aseptic conditions and procedures. Aseptic technique refers to efforts to maintain a sterile field during a procedure to prevent infection. In order to maintain the highest aseptic techniques, it was decided to move the DBX Putty process to isolators for their ease of use in cleaning and decontamination. The process whether conducted in a clean room, biological safety cabinet, or an isolator is largely the same with the exception of the decontamination cycle.

In order for this process to be economically feasible, the decontamination cycle had to take less than 2 hours.  If the decontamination time exceeded 2 hours, then it would not be cost effective enough to warrant the change from clean room processing to isolation processing. The choice was between vapor phase hydrogen peroxide and chlorine dioxide gas. Both methods are registered with the US-EPA as sterilants, and both have been used in clean room environments and in isolators. The VPHP process produced varying amounts of condensation with potential for poor distribution and penetration abilities into gaps and small openings. Based on these limitations, chlorine dioxide, a true gas at room temperatures, was chosen due to its fast cycle times and evidence of its effectiveness.  With the reduced cycle times, MTF’s decision to move forward with isolators became feasible. The isolators eliminated the need for using 2.5 ISO 4 clean rooms and provided true aseptic processing.  The chlorine dioxide gas generator and isolators worked together to provide a simple and seamless systems integration.

To learn more about the Musculoskeletal Transplant Foundation’s selection, design, and validation of isolators for aseptic processing with chlorine dioxide gas, read Nick Barbu and Robert Zwick’s article in Pharmaceutical Engineering here.

Material Compatibility - Electronics

Material compatibility remains one of the largest question marks for those looking to use chlorine dioxide gas, and there’s a lot of conflicting information on the topic.  Chlorine dioxide gas cannot be stored and shipped, so it must be generated at the point of use.  The method of generation, and its resulting purity, has a great impact on the material compatibility of the chlorine dioxide gas product being used.  One of the first large scale decontamination projects utilizing chlorine dioxide gas was the oft referenced Hart Senate Building decon performed in November 2001.   It was performed by a company who previously used its CD gas technology for controlling odors in oil wells. As material compatibility was never an issue in this previous application, they used a less refined process of generation which contained acidic byproducts. When used in the Hart Senate Building, some material issues and corrosion occurred. ClorDiSys was established after this, and our chlorine dioxide gas is generated by passing a low concentration chlorine gas through a proprietary sodium chlorite cartridge to convert the chlorine gas into pure chlorine dioxide gas. Our process does not leave a residue and does not require any additional clean up once the gas has left the space.

ClorDiSys has done studies with electronics and found that they stand up well after multiple exposures. Computers have been exposed to the gas for over 25 cycles and have been fully functioning afterward. In fact, chlorine dioxide gas was chosen to decontaminate the inner chambers of a $3,000,000 Transmission Electron Microscope over hydrogen peroxide vapor because of its superior material compatibility as proven through manufacturer testing. The US Environmental Protection Agency (EPA) commissioned a study exposing computers to chlorine dioxide and hydrogen peroxide over the course of 6 months. Below are the test results showing chlorine dioxide had the lowest amount of failures.

Not all chlorine dioxide gas products are the same, and we understand the hesitation considering some of the information available regarding corrosion.  That’s why we offer free* material testing to give confidence that our chlorine dioxide gas will be safe on your materials and sensitive items.

* Testing is free for a reasonable amount of items.  Shipping not included

Ultraviolet Light in HVAC Systems

Mold, mildew, and dangerous diseases, such as Anthrax, Influenza, Measles, Smallpox, and Tuberculosis, are often spread through airborne transmission. Mold spores easily disperse, wreaking havoc in the new environments they land upon. A solution to continuously combat harmful organisms is the introduction of ultraviolet light disinfection. Ultraviolet light is divided into UV-A, UV-B and UV-C rays. It is the wavelengths in the UV-C spectrum, specifically 265 nm, that offers the greatest germicidal potential.  When a microorganism is exposed, the nuclei of the cells are altered due to photolytic processes. This process prevents further replication and causes cell death.

Ultraviolet light disinfection systems can be placed directly within HVAC ducts to both eliminate and prevent mold, mildew, and other organisms from forming and spreading.  Unlike HEPA filters that solely trap organisms, allowing them to flourish and possibly be re-released into the environment, UV-C kills organisms, eliminating that risk. Placing UV-C disinfection units within the HVAC system provides a continuous disinfection cycle with no harmful effect to anyone present in the space.  Units can be placed in the supply and the return to maximize the benefits.  Units placed in the return ducts have an even greater benefit, because the slower air velocity allows for additional exposure time. Ultraviolet light disinfection is an easy, hands-off, chemical-free way to reduce the risk of mold and mildew from developing and the spread of disease causing airborne organisms.


Attend the upcoming UV Light for Healthcare webinar on July 19th and UV Light for the Life Science and Pharmaceutical Industries on August 7th to learn more.

Can Chlorine Dioxide be used with Organic Foods?

ClorDiSys is occasionally asked if chlorine dioxide can be used in organic foods or in organic processing facilities. The short answer is yes.  More specifically, according to 7 CFR part 205, SUBCHAPTER M—ORGANIC FOODS PRODUCTION ACT PROVISIONS, the use of chlorine dioxide is allowed, but it comes with some restrictions. Its use is permitted for Livestock Management Tools and Production Aids, for Processing Sanitizers and Cleaners, and for Crop Management Tools and Production Aids. The common restriction across all three applications is the residual chlorine levels in any final rinse water or water in direct contact with food products or animals. The water cannot exceed the maximum residual disinfectant limit under the Safe Drinking Water Act (0.8 mg/L or 800 ppb). Reference the label of the product you are using to establish proper use corresponding with such restrictions. Visit the websites below for additional information to see if your organic operation qualifies for chlorine dioxide usage.

REFERENCES

• Organic Materials Review Institute, https://www.omri.org/generic-material/chlorine-dioxide

• Title 7 Agriculture → Subtitle B → Chapter I → Subchapter M → Part 205—NATIONAL ORGANIC PROGRAM https://www.gpo.gov/fdsys/granule/CFR-2011-title7-vol3/CFR-2011-title7-vol3-part205/content-detail.html

Case Study: Decontamination of Tented Equipment or Area

Food production facilities are facing greater scrutiny from both the public and the government to provide safe foods. Advances in environmental monitoring and microbial sampling have brought to light the shortcomings of the food industry’s sanitation methods. While there are many reasons for recurring contamination by a persistent pathogen, insufficient cleaning and decontamination is the most common. ClorDiSys Decontamination Services can be utilized for a variety of applications within the food industry from tented pieces of equipment up to entire facilities. Tenting an area is an application that we’re seeing more of lately, especially in facilities that have more of an open design and floor plan.

One example of this application is when our service team decontaminated a confectionery facility’s roaster. The roaster had caught fire and was extinguished by the fire department.  Worried the water used to put out the fire contained organisms which could contaminate their production line, this company wanted to clean the equipment before production started again.  Some of the equipment’s interior was not easily accessible for the in-house sanitation team, so once the majority of cocoa powder was removed, the company opted to decontaminate with chlorine dioxide gas. That equipment was tented and fumigated, as the rest of the room was not deemed a concern. The setup and decontamination of the roughly 8,000 ft3 space took place in 1 day and successfully provided a 6-log sporicidal reduction of all surfaces within the equipment.

ClorDiSys’ Decontamination Services can be arranged for contamination response or preventive control needs. Visit our team at booth #609 at the IAFP Annual Meeting in Salt Lake City July 8-11th to learn more!

Case Study: Used Equipment Decontamination

Our Decontamination Service Team recently completed a decontamination of a used bacon slicing line for a food company.  Because it was a used piece of equipment, the company did not want to bring it into the facility without being decontaminated first. This was not only to preserve the current sterility of their production area, but also to ensure safe food production once the line was in use. The slicing line was placed within a trailer which provided a sealed chamber for safe decontamination. 10 biological indicators were placed within the trailer and equipment in order to show that a 6-log reduction had been achieved. Once the trailer was sealed, the decontamination started.  The entire setup and decontamination took 4 hours from start to finish, when it was safe to open the trailer and bring the equipment into the production area. All biological indicators came back negative for growth verifying that the decontamination was successful. Production was able to start on the bacon slicing line shortly after being installed within the production area, and the company has been safely producing food since.

Contaminated piece of equipment in your facility? Call ClorDiSys at (908) 236-4100 or email the Decontamination Service Team at service@clordisys.com.

Continuous vs. Pulsed UV-C

Not all ultraviolet disinfection is alike. In fact, not all ultraviolet light is alike. Ultraviolet light is divided into UV-A, UV-B, and UV-C rays. It is the wavelengths in the UV-C spectrum which offer the greatest germicidal potential. Some UV disinfection systems, like xenon pulse UV, use the full spectrum of ultraviolet light to disperse germ-killing energy. It is claimed that the xenon pulse is a more effective way to kill harmful bacteria because of its similarities to punching a wall, more punches will weaken it better than one. However, light is not a fist. It is a form of energy, and continual energy is more effective than turning it on and turning it off. Additionally, bulbs generating UV-A, UV-B, and UV-C wavelengths are inherently less effective in disinfection than continuous UV-C.

The US Veterans Administration commissioned an infection prevention research team led by Curtis Donskey, M.D., to conduct an independent study of continuous ultraviolet disinfection versus xenon pulse UV disinfection. The study tested a continuous UV-C robot which was run for the same length of time from the same point in the room as a pulsed xenon (PU-UV) unit.  The results showed surprisingly low pathogen kill rates for the pulsed xenon device, about .5 log for both C.diff and VRE, even as close as 4 feet.  The continuous UV-C robot demonstrated a much higher CFU reduction for the pathogens C. difficile, MRSA and VRE.  The study states, “PX-UV was less effective than continuous UV-C in reducing pathogen recovery on glass slides with a 10-minute exposure time in similar hospital rooms” and “the UV-C device achieved significantly greater log10 CFU reductions than the PX-UV device”. Not only did the continuous UV-C robot in the study show much stronger disinfectant results, but that it was not run for its entire cycle time. The study calls attention to the dangers of bold claims and trying to complete a disinfectant procedure too quickly.

Chart from VA Donskey study: Study results showing log reductions achieved by a UV-C and pulsed xenon devices
when run for the same time (10 min.) at the same distance from glass microscope slides (4 ft).
(PRNewsFoto/Infection Prevention Technologies)

To read more on the comparison of these two technologies, click here.

Decontamination of Spiral Freezers

The biggest challenge in successfully cleaning spiral freezers is trying to reach all the surfaces.  Spiral freezers are constructed with minimal clearances, making it hard to use traditional cleaning techniques such as the spraying of liquid chemicals.  The interior is too tight to maneuver cleaning equipment properly and operate it effectively.  Cleaning every nook and cranny inside of a spiral freezer is a very difficult task when taking into consideration all of the internal components, all of the hard to reach crevices, the difficulty in maintaining the correct contact time of the chemical being used, and the difficulty in the agent reaching all surfaces.

Chlorine dioxide gas has been proven effective at eliminating listeria from within spiral and tunnel freezers. ClorDiSys’ chlorine dioxide gas is made using a proprietary generation method and is registered with the US EPA as a sterilant providing a 6-log (99.9999%) reduction of all viruses, bacteria, fungi, molds and spores. As a true gas, chlorine dioxide naturally fills the spiral freezer evenly and completely, and with a molecule size smaller than the smallest organism, there’s no surface that is safe for pathogens to hide. Gaseous CD is the only decontaminant that penetrates water and decontaminates both the water and the surface beneath, which is important for spiral freezers that typically have condensation issues.

One facility which produced frozen sausages had a persistent listeria problem, resulting in consistent positive swabs. After one treatment with chlorine dioxide gas, the facility was able to eclipse 16 weeks without a single positive swab after testing 2-3 times per day. CD gas decontamination has been written into a quarterly preventive maintenance schedule.

Attend our Food Facility Decontamination Services webinar on June 7^th to learn more or stop by Booth #10 at the North American Food Safety and Quality 2018 on June 5-6^th to further discuss.

How Ultraviolet Light Help Prevent The Spread Of Ebola

While combating the highly infectious Ebola virus disease (EVD) outbreak in West Africa, aid workers and other visitors have been inadvertently exposed and contracting the virus. In 2014, a number of infected individuals were evacuated from Africa and returned to the United States for treatment. The Nebraska Biocontainment Unit (NBU) was one of the several receiving hospitals for these patients. The NBU and Omaha Fire Department’s emergency medical services coordinated patient transportation from the airport to the high-level isolation unit. Following patient admission into this unit, biocontainment staff members relocated the ambulance to an isolated, controlled-access area to be decontaminated. All surfaces in the cab and patient compartment were thoroughly wiped with bleach solution. Then, as a final disinfection step, the back of the ambulance was exposed to ultraviolet light.

Ultraviolet light is a specific part of the electromagnetic spectrum of light that offers bactericidal effects. It is the wavelengths in the UV-C spectrum, which offer the greatest germicidal potential. UV-C provides a dry, chemical-free, and residue-free method of disinfection effective against bacteria, viruses, fungi and spores. For this reason, ultraviolet light disinfection was not only used in the ambulances, but as the final step in decontaminating medical equipment, patients’ rooms, and bathrooms after patients were discharged. Acknowledging the known limitations that UV-C only disinfects the areas light can reach, the Nebraska Biocontainment Unit used four ClorDiSys Torch systems in tandem to ensure the proper exposure was achieved to inactivate the Ebola virus.

Read more about the effective use of ultraviolet lightdisinfection against Ebola here.

Learn more about ClorDiSys Solutions’ Torch here.

How Often You Should Schedule Preventative Decontamination

Over the past couple of years, we've noticed a shift within our decontamination services projects.  At first, all projects were in response to active contaminations.  More recently however, we've noticed a shift as more of our decontamination service projects have been scheduled as part of a preventive sanitation effort, aimed at providing a more thorough kill than traditional sanitation can achieve.  One of the more frequent questions we get when discussing preventive decontamination is, 'how often should we decontaminate?'  It's a great question, and its one that doesn't have a simple answer as every situation is different.

When discussing the frequency and scheduling of preventive decontamination, the best first step is to review your environmental monitoring data.  Sometimes, there's a trend within the data that can help guide the process along.  In these situations, we would propose to undercut that trend so that the decontamination takes place before the next positive "is expected."

Example:
A processing area shows positive environmental monitoring swabs approximately every 6-8 months. 

Proposed Preventive Schedule:
Decontamination every 5 months

For areas where there is no easy to determine a trend in positive environmental swabs, another approach must be taken.  In these situations, the following factors should be considered:

• The environment itself (a room, spiral freezer, entire processing area, etc...)
• The risk level of the product and environment (raw meat vs. canned foods vs. produce vs...)
• Historical environmental monitoring data
• Downtime / Availability of the space (24/7 production, 24/5 production, yearly shutdown, etc...)

We've seen preventive decontamination schedules ranging from daily (for the decontamination of brushes and dry cleaning tools within a Decon Chamber) to quarterly (Spiral Freezers and Aseptic Fill Rooms) to Annual (Processing Areas and Production Rooms).

If you're interested in learning more about Preventive Decontamination as a supplement to your sanitation program, contact us at 908-236-4100 or visit www.clordisys.com/foodsafetyapp

Chlorine Dioxide vs. Chlorine Dioxide: Choosing the Right Provider

ClorDiSys Solutions approaches decontamination differently than other chlorine dioxide gas companies. We strive for excellent process control, high quality, and outstanding safety. Our chlorine dioxide gas is registered with the US EPA as a sterilant. It is proven capable of providing a 6-log (99.9999% reduction) of all viruses, bacteria, fungi, molds and spores. Our chlorine dioxide gas is the only one registered at this highest antimicrobial level.

The ClorDiSys method of generating chlorine dioxide produces a 100% pure gas. Other methods of generating chlorine dioxide mix an acid and a base which forms a chlorine dioxide solution which is then off-gassed to fumigate a space. That generation method produces two acidic components, acidified sodium chlorite and chlorous acid, alongside chlorine dioxide which makes these methods more corrosive. Our method of generating pure chlorine dioxide gas is accomplished by passing a low concentration chlorine gas through a proprietary sodium chlorite cartridge to convert the chlorine gas into pure chlorine dioxide gas. This allows our process to be safe when decontaminating stainless steel, galvanized metals, anodized aluminum, epoxy surfaces, electronics, and the most common materials of construction. Typically, if water will not corrode an item, neither will our CD. ClorDiSys’ chlorine dioxide gas has been proven to the FDA to leave behind no measurable residue. Once the gas has been removed, the area is safe and does not require additional cleanup.

ClorDiSys uses a highly accurate UV-vis spectrophotometer to measure the concentration. Photometers are able to measure precise locations, such as hot spots, in order to provide greater confidence (and data for regulators) that those locations underwent a specific exposure dosage. Our Decon Service team measures the concentration of chlorine dioxide gas throughout the entire process at multiple locations in order to ensure that all locations reach the proper dosage necessary to achieve a 6-log sporicidal reduction. Other chlorine dioxide gas decontamination processes monitor one location using a less accurate chemical sensor, making the process less repeatable and reliable.

Click here to learn more about our process or join us online May 15^th at 1:00pm EST for CD Gas 101 webinar.

Choose Prevention over Recall Apprehension

A recall can be extremely detrimental to a company both at the time of recall and well into the future. Avoid major consequences like production stoppages, adverse media attention, loss of consumer trust, and civil suits or federal investigations by being prepared and investing in routine preventive decontamination. Traditional sanitation methods have difficulty truly eliminating pathogens from hard-to-reach areas.  This is what allows growth niches and harborage sites to become established and create “resident strains” in your facility.  Supplementing your routine sanitation program with a high-level decontamination method can eliminate the pathogens within niches and harborage sites to provide a cleaner and safer environment.

ClorDiSys offers an all-encompassing Preventive Food Safety Program which brings together industry experts from complimentary organizations to help lead the way towards safer food manufacturing. Get an outsider’s perspective on your current Food Safety Program to gain insight and eliminate possible issues that are currently being overlooked. Through a single purchasing source, you can select from a variety of services not offered by a single organization to help find and address the gaps in your food safety program and ensure that your reputation stays in high regard among consumers.

Stop by to chat and learn more at the 20^th Annual Food Safety Summit next week or log in to our Preventive Food Safety Program webinar on May 22^nd.