High containment gloveboxes (HCG) have been used in the pharmaceutical industry for containment of potent compounds, along with providing specific environmental conditions, for years. These types of glovebox design fit well into the Class III Bio Safety Cabinet classifications but provide even better environmental attributes than the standard BSC designs.
If you review the classification design requirements provided in the table, you will notice that the BCS III design parameters actually describe a typical high containment glovebox. They are totally enclosed, HEPA filtered, and the operator utilizes gloveports for manipulation of pathogens. In a high containment glovebox, you have the same parameters but are working with potent compounds and not biohazardous materials.
In order to achieve what you need to with regard to choosing any type of environmentally controlled device, you need to first identify and assess the process. Then you can compare a HCG with a BSC cabinet and make the comparison between the two.
HCG has added benefits over a typical BSC cabinet:
- HCG designs are more robust, and they have a once through airflow requirement and do not recirculate. So everything in the glovebox is not “re-contaminated.”
- Relative humidity can be controlled with a nitrogen or argon purged environment. Nitrogen/argon will provide less than 1 percent relative humidity, at atmosphere or a slight negative pressure.
- The HCG can accommodate the same requirements as the Class III BSC but with a purged environment that can provide less than 2 to 3 percent oxygen which can be very instrumental in controlling some bacterium.
- Less turbulent than the BSC III and so finite weighing activities can be done. HCG have a cross flow vs. a downward/upward air flow in BSC cabinets.
- HCGs can be rated hazardous area with a Class 1, Div 1, groups C & D, F & G.
- UV lighting can be used for decontamination.
- Passivation of the main chamber, which provides better cleaning attributes to the surfaces of the HCG.
The commonality of HCG and Class III BSC systems are important to identify as these key features need to be included for both types of systems:
1. HEPA Filtration. In and out.
2. Airlock or dunk tank prior to the main chamber.
3. Gloveports and gloves.
4. Laminar flow is not used in Class III BSCs or HCGs.
5. Exhaust in dedicated and not into the room.
When evaluating the process for biohazardous contaminants, the following principles and methods need to be applied:
1. Risk assessment:
a. Recognize hazards and identification.
b. Exposure potentials.
c. Frequency of occurrence.
d. Evaluation of work tasks and equipment
e. Assigning protective measures to specific tasks.
2. Biological contamination evaluation:
a. Risks for workers.
b. Reduction of exposure potentials by evaluating the infectivity and transmissibility.
3. Concentration and enclosure:
a. Confinement of the biohazard
b. Use of one system. Less risk than if work is done in two or more systems.
4. Exposure minimization:
a. Fully enclosed system.
b. Automated features, such as conveyers, specialized equipment.
c. Barrier system between the operator and biohazardous compounds.
5. Physical containment:
a. Barrier for all aspects of the process.
b. Prevention of any aerosol or droplet generation.
d. Robotics or automation of the process.
6. Hazard minimization, activities if an exposure occurs:
a. Safety and contingency plan.
b. Emergency procedures and training.
c. Vaccination, if applicable.
Design is the key to the safety and operational features of any device used for environmental conditions or control. When looking at the initial design, it is key to establish the process flow and operating sequences. What are we going to handle? What mechanics are required to handle the materials of containers?
These items come into play and should be incorporated into a full scale mock up to be assessed by the operators prior to final fabrication. Testing of any automation requirements should be completed and proven. These type of facsimiles will prove concepts and workability of such systems.
Once you have decided on the best system and design, testing needs to completed. Testing methods are standard and can be applied to the HCGs. Testing of the HCGs would conform to the industry standard and include the following:
Air quality/flow and microbiologic testing.
1. Testing should only be done by a third party.
2. Testing needs to be relevant to the biohazardous substance.
3. Testing of the HEPA filters by DOP with particle analysis a ROYCO counter.
4. Tests using a micro nebulizer.
5. Bacterial or BI are placed in the glovebox and a decontamination cycle is run and submitted for results.
6. Air changes per hour need to be verified.
Containment/ cleaning validation:
1. Third party containment testing can be completed using the ISPE Guidelines.
2. Riboflavin testing for verification of CIP (clean in place systems).
Testing should be robust and conform to industry standards for both types of systems.
The HCG can be used for any biohazardous application with the added benefit of better control, a more robust design, and (typically) a lower cost.
The processes can utilize automation, which in turn provides the optimum in operator safety and concise process manipulations while under a stringently controlled environment. The process can be completed in one system, thus saving floor space and generating less utility requirements — all while reducing risk of contamination.
This article appeared in the November/December 2015 issue of Controlled Environments.