In 1994, Dräger introduced the first electrochemical hydrogen peroxide (H2O2) sensor for monitoring low concentrations of vaporized hydrogen peroxide (VHP). VHP became the preferred substance for decontamination due to its bioactive effect of killing bacteria. Today it is used in filling machines, barrier isolators, glove boxes, workbenches, and entire rooms.
Vaporized hydrogen peroxide (VHP) is generated by actively vaporizing an aqueous hydrogen peroxide (H 2 O 2 ) solution and injecting it into a room. Achieving a high level of microorganism bio-decontamination requires a defined high VHP concentration and exposure time. VHP is rated harmful to humans. As a result, many countries have imposed an occupational exposure limit value. Values in the United States for both 1993-1994 ACGIH TLV and current OSHA PEL are 1 ppm (1.4 mg/m 3 ) TWA. Staff outside a fumigated room or facility must be protected from accidental contact with H 2 O 2 vapor. At the end of a sterilization cycle, the room or volume is rinsed with fresh air. An air analysis is necessary before it is safe for staff to enter the room or bring in new, sensitive material for a production stage. The concentration of H 2 O 2 must be reduced through ventilation to non-hazardous levels, usually less than 1 ppm.
The generator that creates the H 2 O 2 vapor for sterilization can also pose a risk to staff, which is why the generator‘s environment and connecting hoses need to be monitored for H 2 O 2 gas leakage.A risk analysis is necessary to satisfy regulatory guidelines. The purpose of the analysis is to identify all potential sources of risk, and to define measures to control exposure using gas measurement instruments, personal protection equipment and operating instructions.
Properties of VHP
VHP is a vapor – not a gas. This means that the H 2 O 2 concentration in the air never exceeds the vapor pressure at the corresponding temperature (and pressure). Above the saturation point (dew point), H 2 O 2 vapor starts to condense as an aerosol or on surfaces.
H 2 O 2 is completely soluble in water. Solutions of 30% to 35% H 2 O 2 are common for applying VHP. As vaporization of water is 15 times more effective than that of H 2 O 2 , the aqueous solution has to be actively vaporized, such as on a hot plate. When H 2 O 2 is exposed to condensed water, the solution absorbs H 2 O 2 and the VHP concentration in the ambient air diminishes.
H 2 O 2 is an unstable compound. It decomposes to form oxygen and water. Thus, the concentration of H 2 O 2 is constantly decreasing, which is why stabilizing chemicals are added to the aqueous solution. During active vaporization, these chemicals enter the fumigated room, and may condense on surfaces.
H 2 O 2 is highly absorbent. A loss of concentration through absorption by the surrounding air and on surfaces can be observed. To saturate a surface requires a certain quantity of VHP. Thus, smaller concentrations are more heavily influenced than high concentrations. In pumped systems, the hoses adsorb H 2 O 2 on their surfaces before it reaches the sensor and can be indicated. This loss and the accompanying delay in measurement must be taken into account. When rinsing with air, this effect extends the rinsing times of H 2 O 2 outgassing from the surfaces. DrägerSensors® measure H 2 O 2 vapor as a volume concentration (ppm).
H 2 O 2 is a chemically aggressive compound. Dräger transmitters and sensors are made from a chemical-resistant plastic (polyamide 12 blend). If high VHP exposure will be frequent, the transmitter should be installed outside the VHP atmosphere in a way that only the sensor extends into the measurement room (remote sensing). Any use that deviates from specified conditions must be verified by users on their own authority.
Because of the physical and chemical properties described above, calibration with hydrogen peroxide is not easy to perform. VHP has to be generated with resources under laboratory conditions, and the concentration verified with an analytical device. This is not possible in the field.
Dräger offers factory-calibrated sensors. The calibration information is stored in the sensor. For recalibration, the sensor can be removed from the transmitter and sent to a Dräger Service station for H 2 O 2 calibration. A spare sensor continues to measure in the interim. Sensors are supplied with a calibration certificate, which documents the measurement values before and after calibration. DrägerSensors for H 2 O 2 have a cross sensitivity to sulfur dioxide (SO 2 ). The empirical ratio of sensitivity between SO 2 and H 2 O 2 is known as relative sensitivity. This value has a statistical spread and does not have a guaranteed constant time. The tolerance for new sensors is ±10 %. For reasons of accuracy and reliability, it is therefore preferable to calibrate with the H 2 O 2 target gas instead of a substitute calibration with SO 2 . Other performance specifications are available in the datasheet.
Dräger H 2 O 2 Monitoring Solutions
Workplace monitoring and leakage detection
For personal protection, workers should wear a portable gas detection device that alerts them to exposure wherever they are. For area monitoring, a stationary gas detector monitors a defined area. It is important that stationary gas detectors be placed in an ideal location to detect gas quickly and reliably. To ensure this, it is necessary to inspect and consider gas dispersion and airflow.
Cycle parameter control and safe entry measurement
A sterilization cycle for isolators or cleanrooms can be divided into four phases. The first phase in a fumigation cycle is dehumidification. During this phase, air from the target room is cycled through a dehumidifier to reduce air humidity. This takes about 20 minutes, depending on the volume of the room. In the conditioning or fumigation phase, hydrogen peroxide is actively vaporized at a pre-set injection rate and fed into the room. This takes about 30 minutes. Sterilization is sometimes also called the “dwell” phase. The VHP concentration is kept constant for a predefined duration of exposure Pre-configured process parameters are applied during this phase.
The parameters have been determined in the application validation for the required microbiological extermination rate.
Ventilation is the longest phase in the cycle (up to 5 hours). VHP is no longer pumped into the room. The air is fed through a catalytic scrubber or replaced with fresh air to lower the concentration of H 2 O 2 to a pre-defined threshold value. The fumigation cycle, specific to each device, must be qualified and validated in compliance with Good Manufacturing Practice (GMP) rules during consignment. Chemical (CI) and biological indicators (BI) in the device or room measure the extermination rate. The programmed process parameters for VHP fumigation are derived from this.
Pharmaceutical companies with single-use or stainless-steel bioreactors are trusting JM Canty’s visual analyzers for boosting production, efficiency, and quality control.
One of our New Jersey pharmaceutical customers have chosen the Canty Biocam, specifically for foam control, for its reduction of anti-foam usage and allowing for more product per batch.
A fermentation user reported up to a 30% drop in anti-foam usage per batch, and another reported the ability to roughly increase batch size by over 25%.
Bristol Myers Squibb conducted its own testing of the Canty analyzer for cell viability and found that CantyPharmaflow Imaging analyzer demonstrated the ability to measure early and late apoptosis, correlating to biomarkers such as Caspase and Nexin.
How can the Canty cameras help your fermenters and bioreactors? Ask one of our engineers!
Check out how JM Cantys foam detection works in this short video!
This past year has seen massive investments in vaccine research and development as well as production efficiency. The pharmaceutical and biotech market utilizes either stainless steel tanks or single-use tanks in one of the main chemical processes for this development – fermentation. During the fermentation growing process with bioreactor vessels, mass spectrometry analyzers have traditionally been used to measure exhausted gases from the process. Analysis of these gases can determine respiration metrics – specifically looking at concentrations of oxygen, carbon dioxide, nitrogen and argon in the sample stream. These values are then used to determine the oxygen uptakes rate (OUR) and carbon dioxide evaluation rate (CER).
In 2019, Schneider Electric’s AIT gas analyzer division released a new mass spectrometer for this very application – the MGA 1200CS series. The MGA 1200CS was voted 2019 Product of the Year by the ISA Analyzer Division due to it drastically enhancing the respiration analysis by coming out with a mass spectrometer that has a 3 second response time: 1 second for purge, 1 second for measurement, 1 second for changeover to the next sample stream. With a vastly quickened response time, fermentation control can now be quickly adjusted and automated based upon the mass spectrometers readings allowing pharmaceutical research, development, and production to make a drastic jump forward technologically.
One of the world’s leading vaccine manufacturers has been successfully testing the system for the past year. By utilizing a full multi-stream sampling system and mass spectrometer deployment in labs with multiple bio-reactors. The system can do up to 100 sample streams with the appropriate sampling system.
The Schneider Electric MGA is ready for world deployment for any pharmaceutical or biotech applications where fermentation or bioreactors need quicker speeds!
Eurotherm offers a comprehensive range of scalable and flexible solutions which will satisfy the requirements of environmental and stability chamber monitoring for Pharmaceutical and Bio-Pharma industries. These solutions unify the environmental and security data from the manufacturing area for presentation to plant or laboratory managers and operators.
See the application note related to these products here: Pharmaceutical Environmental & Stablility Chamber Monitoring