Q&A with James T. Wagner,
Controlled Environment Consulting
Pharmacy Purchasing & Products: What value do CAIs and CACIs bring to the compounding operation?
James Wagner: Because compounding aseptic isolators (CAIs) and compounding aseptic containment isolators (CACIs) provide a contained environment for compounding, they can be an excellent solution for hospitals with low compounding volumes or facilities without a cleanroom to compound sterile preparations in a cost-effective and compliant manner. Using a CAI or CACI also can be an effective short-term solution for managing compounding while a USP <797>-compliant cleanroom is under construction.
PP&P: What are the certification requirements for isolators?
Wagner: CAIs and CACIs should be certified to the Controlled Environment Testing Association’s (CETA) CAG-002-2006,1 rather than simply meeting the manufacturer’s specifications. (See TABLE 1 for CETA’s Mandatory Field Tests.) It is important to certify your isolator to an industry-based standard, as this robust test process will indicate whether this critical equipment is operating properly. USP <797> recommends that primary and secondary engineering controls be certified in accordance with CETA CAG-003, which in turn recommends that isolators be certified to CAG-002.
PP&P: What steps are necessary to ensure appropriate isolator use?
Wagner: Developing effective policies and procedures (P&Ps), training materials, and a competency checklist to measure staff adherence to P&Ps will ensure the isolator is used as intended. When developing P&Ps, include processes for transferring materials into and out of the isolator, removing sterile wrappings, and disposing of waste. Once P&Ps are developed, staff training materials should be generated based on these P&Ps. In addition, be sure to develop a competency checklist to help staff adhere to the P&Ps moving forward. The competency checklist should include all tasks required to perpetuate safe use of the isolator. (See PP&P’s December 2013 article, Operating and Maintaining Primary Engineering Controls, for direction on creating P&Ps.)
When developing P&Ps, training materials, and a competency checklist, pay close attention to the following:
Establish appropriate use of first air. In order to maintain an ISO class 5 environment at the critical site throughout the compounding process, the user must make sure the direct compounding area is appropriately located in a good unidirectional airflow stream. To identify the ideal location for the direct compounding area, perform an airflow smoke pattern test, which is a requirement of USP Chapter <797>. Although this test is commonly regarded as a nuisance that must be performed as part of the certification process, it is actually a critical element in ensuring safe use of the isolator. The smoke test will illustrate where first air is ideal, making it easy to determine the optimal setup for the isolator, including where to remove sterile components from their packaging and where to establish the direct compounding area.
Perform a dynamic particle count survey. Good aseptic processes can only occur when the unidirectional airflow stream is free of turbulence. Should turbulence be created within the space, particulates will enter the direct compounding area, and possibly the compound itself. To avoid this risk, conduct a dynamic particle count, wherein particle counts are collected while technicians complete the entire compounding process. Performing the test is straightforward: position the particle count probe six to 12 inches upstream of the critical site, under the ISO-classified first air. If you are getting good first air, the dynamic particle count should not measure any particles, even when performing activities that typically generate a large number of particles (ie, opening sterile wrappings).
Develop a process for introducing compounding components into the isolator. Prior to bringing compounding materials into the isolator, it is necessary to determine the length of time required to purge the pass-through chamber. Ideally, the manufacturer can provide this information, and it can be included in P&Ps and training materials; most isolators require one to two minutes. If the manufacturer cannot provide this information, develop the process internally, working closely with your certifier. CETA CAG-002 has test procedures to verify the material transfer process (2.09 Preparation Ingress and Egress Test).
Determine a waste-disposal procedure. Determining an appropriate method for waste disposal depends on the isolator. If the isolator has no trash chute, set trash aside and remove it through the ante-chamber once compounding has been completed. The disposal process is simplified for isolators with chutes for sharps and trash; however, an issue of concern is ensuring that bags or containers are tightly sealed to prevent any ingress of contamination. This is particularly important for CACIs, given that they operate under negative pressure, and as such, any leak could introduce contamination directly into the critical site. The timing for transferring materials out and confirming tight seals on trash containers must be incorporated into training materials. CETA CAG-002 has test procedures to verify the integrity of the enclosure and trash chutes (2.06 Particle Containment Integrity and Enclosure Leak Test).
Create an isolator cleaning process. Another process that must be developed, captured in P&Ps, and included in the staff-training program is the correct method for cleaning the isolator. (See PP&P’s September 2013 article, Requirements and Best Practices for Sanitizing Engineering Controls.) Often, the isolator manufacturer will provide cleaning guidance. Because reaching every area of the isolator can be challenging, special isolator cleaning tools are usually required. Cleaning should occur daily, as well as before and after every process.
Develop a procedure for the correct use of sterile gloves in the isolator. One preparatory step that may be overlooked is the USP <797> requirement to use sterile gloves. If sterile gloves are placed on the sleeve of the isolator, they may no longer be sterile by the time the operator puts them on. A better method is to put non-sterile, nitrile gloves on the sleeves of the isolator, place sterile gloves inside the isolator, and then put the sterile gloves over the top of the isolator gloves; that way, only the sterile gloves come into contact with the product.
PP&P: What PPE should be worn when using CAIs and CACIs?
Wagner: With aseptic compounding, the goal is to prevent the introduction of contamination into the isolator. The isolator manufacturer typically provides information on what PPE is required when working with nonhazardous sterile preparations, such as using gloves during any product transfers. However, when compounding hazardous drugs, full gowning is required. Full PPE is always necessary any time hazardous drugs are being handled, no matter what engineering control is in use.
PP&P: How should glove sleeve changes be handled?
Wagner: Ideally, the isolator manufacturer will provide a methodology for changing gloves. Generally, one glove slides over the top of the other, and using the plastic collar, the gloves can be changed without exposing the isolator to the outside environment. However, it takes a bit of practice to do this well so that the isolator remains closed. This is particularly concerning for negative pressure CACIs, as there is the potential for introducing contamination into the isolator if the process is not executed correctly.
Some isolators provide quick-change sleeves that allow you to mount the new glove onto a ring and push the ring into a collar, which then pushes the old ring out. A quick-change sleeve can make glove changes more efficient and sterile while maintaining safe use of the isolator. If glove changes are difficult, the likelihood is high that users will not change the gloves as often as they should. In addition to gloves, the sleeves must be changed on a regular basis; most manufacturers recommend changing sleeves every six months. However, in many cases, more frequent change-outs may be required. At a minimum, thorough daily checks are recommended, due to the potential for contamination in a negative pressure isolator should a small hole go undetected.
Include glove change instructions in P&Ps and training materials. It is critical to remember that developing P&Ps is only the first step in ensuring appropriate isolator use. For P&Ps to be effective, staff must be trained, should understand the intent of P&Ps, and must demonstrate adherence to these P&Ps.
James T. Wagner, principal of Controlled Environment Consulting, has over 30 years’ experience evaluating facilities and primary engineering controls used for aseptic processing. He has served on many industry-standard writing committees and was a member of the expert panel that revised USP Chapter <797>.