Q & A with Carl LaBella, MBA
CSI Testing Inc
Pharmacy Purchasing & Products: How can pharmacy managers successfully plan for a cleanroom construction?
Carl LaBella: Pharmacy managers need to take an active role in the cleanroom design process. Identifying requirements for space, workflow, ceiling height, personnel traffic, electrical power, and building exhaust, as well as other needs, early in the design phase can save money—and headaches—post construction. Designing a cleanroom to best support workflow should not be left solely in the hands of the architect or mechanical designer, input from the pharmacy manager—who best understands workflow needs—is crucial. One helpful practice is to map out workflow on the design blueprint: Sequentially number the steps workers will take, starting with where they enter the room, gown, wash hands, don gloves, and then proceed into the buffer area. Do not forget to account for inspection of finished compounded sterile preparations and the transfer of materials in and out of the room. Draw lines to mark the process flow to assess where conflicts may occur.
It also is important to choose which primary engineering controls (PECs) will be used in the cleanroom early in the project so the space can be designed to accommodate this equipment. When PECs are an afterthought, it is not uncommon to see contractors adjusting cleanroom door widths to install biological safety cabinets (BSCs) or compounding aseptic containment isolators (CACIs). Also, standard ceiling heights can interfere with necessary BSC and CACI exhaust dampers, so this needs to be considered in the design phase as well. Recently we tested a cleanroom where the ante-area sink was inadvertently left out of the design. It is much less expensive to address problems such as these in the design phase rather than after the room is built.
Finally, when planning, keep in mind these rooms need to be maintained and certified every six months, and the design of the room should help facilitate this process. A design that takes this into consideration can translate into cost savings over the life of the rooms. Because testing and certification are charged based on time, a cleanroom that requires multiple technicians or additional time to perform regular tasks, such as ceiling HEPA-filter leak tests, will add to the cost of testing. Consider simple design modifications, such as installing properly designed filter housings with aerosol test ports. While this may add a few hundred dollars to your construction costs, over time it can potentially save thousands of dollars on testing. Enlisting the aid of a qualified certification professional to review the design from this perspective is a key early step.
PP&P: What issues should be considered when installing PECs for hazardous drug compounding?
LaBella: In the 2008 revisions to USP Chapter <797>, specific guidelines for hazardous drug preparation were added—including the requirement that the buffer area where hazardous drugs are compounded maintains a negative air pressure of at least 0.01 inch water column. While more institutions are complying with this guideline, a subsequent problem has cropped up: We have encountered facilities with excessive negative air pressure in their hazardous drug buffer areas—sometimes 10 to 15 times higher than the minimum requirement, and these pressures are too high to be beneficial.
Non-hazardous positive pressure cleanroom design is intended to help keep surrounding particle contamination from entering through wall and ceiling penetrations. The negative pressure specification for the buffer area where hazardous drugs are compounded is meant to contain the airborne hazards; however, when the negative pressure level is significantly greater than 0.01 inch water column, airborne particles from adjacent areas can be drawn into the room under doors, through room penetrations, and whenever the door is opened. After reviewing a number of test reports, we found anecdotal evidence that too much negative pressure leads to high total particle counts. Specifically, ISO 7 hazardous buffer areas demonstrated higher total particle counts than the adjoining ISO 7 ante-area.
Optimally, these rooms should be designed to maintain negative pressure at a reasonable level by balancing the air entering the buffer room through the ceiling supply HEPA filters relative to the exhaust air. Reducing room penetrations that allow particle migration also help. Well-designed negative pressure cleanrooms often include sheetrock ceilings and specialty sealed light fixtures. In some cases, these rooms are even designed with a positive pressure corridor around them to reduce the chance of contamination being drawn in.
Finally, it is important to establish a reasonable pressure range for cleanroom designers to follow to minimize this problem. Presently USP <797> only addresses a minimum negative pressure. We consider a negative pressure range between 0.01 and 0.04 inch water column as reasonable. Designers also should aim to reduce any positive air pressure differential from the ceiling space to the room to minimize particle migration into the room through ceiling tiles, light fixtures, and other penetrations.
PP&P: What steps should be taken to ensure PECs are working properly?
LaBella: PECs are often viewed as infallible devices. And while many are very robust, they still require proper use to uphold aseptic conditions, and in the case of hazardous drug compounding, provide safe conditions for users as well.
Infrequent glove changes are a common problem at many facilities using PECs. Both USP <797> and the National Institute for Occupational Safety and Health (NIOSH) address glove inspection and recommend regular changes to ensure glove integrity. Nonetheless, we commonly find torn or damaged gloves when testing isolators. As a result, this costly equipment is rendered useless due to ineffective gloves that are inexpensive to replace. It is important to follow ASHP’s recommendation that gloves be replaced every 30 minutes during batch production in addition to changing them immediately if torn, punctured, or knowingly contaminated.
In addition, regular testing and certification should be performed by qualified technicians to ensure PECs are working properly. When choosing a certification professional, it is important to make sure that they have received the necessary training; experience alone is not an adequate gauge of expertise. NSF International offers accreditation for individuals certifying Class II BSCs, and while not every cleanroom has a BSC, the principles—such as airflow and HEPA filtration—used to certify a BSC apply to most other engineering controls. Recently, the Controlled Environment Testing Association (CETA) established a written and practical qualification process, the Registered Cleanroom Certification Professional in Sterile Compounding (RCCP-SC) credential, for certifiers who test secondary engineering controls according to the requirements of USP <797>. When choosing a certification professional, checking for these credentials is a good place to start.
PP&P: What measures can be employed to ensure staff is using PECs correctly?
LaBella: USP <797> requires the use of first air in the direct compounding area of the PEC. First air is essentially particle free air exiting the supply HEPA filter of the PEC in a unidirectional manner. It is imperative that this airflow maintains a clear, uninterrupted path through the direct compounding area to protect the critical site. We still see compounding personnel struggling with this concept, as evidenced by cluttered PEC workspaces, unnecessary supplies in the PEC, blocked airflow, covered exhaust vents, and a general lack of understanding of the airflow dynamics of a PEC. Turbulent airflow at or near the critical compounding site caused by poor PEC design, airflow obstructions, or inappropriate hand placement is an enemy of good aseptic practice since it can cause particles to be swept onto the critical site.
Education on HEPA-filtered unidirectional airflow needs to be a basic component of all compounding training programs, and part of this education includes in situ air pattern analysis via smoke studies in the PEC—ideally with personnel simulating compounding actions. This testing involves introducing a neutrally buoyant visible smoke stream into the airstream to verify unidirectional flow at the critical zone.
Even though USP <797> requires this type of testing, many pharmacy managers still resist performing it; they view smoke testing as interfering with operations since it requires taking the PEC or even the cleanroom out of service temporarily. However, the value this test provides cannot be understated and it often is an eye-opener for compounding personnel, especially when air turbulence around their hands or near materials in the PEC is clearly observed. It is not difficult to perform this test and it should be incorporated during sterile drug compounding training. While it is not necessary to have a certifier conduct this testing, keep in mind that a certifier can help highlight common turbulence areas.
Carl J. LaBella, MBA, is the president of CSI Testing, Inc in Plymouth, Minnesota. He has worked as a volunteer board member and association president at the Controlled Environment Testing Association (CETA). Carl earned his bachelors degree at the University of Wisconsin, Madison, and his MBA at the University of St. Thomas in St. Paul, Minnesota. He has presented for the Eagleson Institute, CETA, and ASHP on controlled environments. Carl also has presented on cleanroom operation and design, ISO 14644, USP <797>, aseptic isolator-use in sterile drug compounding, and engineering controls for hazardous drug compounding.