Develop a protocol that ensures sampling begins with the cleanest area and finishes with the least clean area.
USP <797> requires compounding pharmacies to have a sampling protocol in place even if the sample collection process is outsourced. The protocol will identify each sampling location and should include a notated floor plan. Determining the appropriate sampling locations can be a challenge for those without a microbiology background, so we recommend seeking out this expertise. Ideally, sample collection begins with the cleanest area and progresses to the least clean area, although a pharmacy’s layout may not always permit this. The protocol should include any points in the sampling process when the samplers should be re-cleaned. A thorough cleaning should take place at the beginning and at the end of each sampling period. The instrument should be wiped down with 70% isopropyl alcohol in between any area that is, or is perceived by the sampling personnel to be, more contaminated than the following area to be sampled.
There is a misconception that the chemotherapy buffer area is one of the less clean areas. In actuality, it is one of the cleanest areas as the hood and the room are both negatively pressurized and the air in both is HEPA filtered. Thus, the hoods in this room should be sampled first, followed by the chemotherapy IV buffer area itself and the laminar flow hoods in the IV prep buffer area. Any spills should be cleaned up immediately using the chemotherapy spill kit (chemotherapy neutralization kit) and the room disinfected again. If the positively pressured IV buffer area is HEPA filtered then the IV prep/buffer area can be sampled next, followed by the anteroom. Keep in mind that the chemotherapy buffer areas and chemotherapy hoods are negatively pressurized; therefore, any organisms introduced from a contaminated anteroom or an improperly sampled area prior to sampling these locations can result in unacceptable microbial growth and contamination.
Gain staff buy-in to conduct sampling under normal working conditions.
Environmental monitoring should occur while compounding staff is working—ie, the IV compounding areas are occupied—so that samples accurately reflect day-to-day conditions. This active sampling approach allows you to collect samples along the six-inch hood borders where the compounding is taking place. By placing samplers on either side of the staff member while he or she is compounding in the hood, the results will indicate if there is a problem with filtration or airflow across the sterile zone. This approach will clearly demonstrate if airflow is being blocked by manipulations during compounding or if supplies or finished products are being placed in the hood in a manner that blocks airflow. Target sampling locations should include areas where the greatest disturbance is taking place, such as in vertical or horizontal flow hoods with multiple technicians or equipment (eg, with an automated compounder) or in a hood used specifically to compound total parenteral nutrition. Areas in the IV prep room with heavy storage and in the anteroom near any sinks or hand blowers also should be targeted.
Oftentimes, staff members express trepidation when someone enters the cleanroom to perform environmental monitoring while they are in the midst of compounding. They frequently offer to leave and return after the testing. While it may seem more efficient to collect samples in an empty room, this approach is not recommended because it does not give a full picture of an active environment in use. Assuring staff that the equipment will not introduce contamination into the environment and underscoring that it is the environment being tested, not their techniques, should facilitate acceptance of active sampling. The IV room manager should explain in advance the goal of environmental monitoring and encourage staff to feel comfortable compounding during the testing process; the better staff understands compliant practices, the safer your CSPs will be.
Purchase the right equipment for the environment.
Choosing the right air sampler involves evaluating each product in light of the facility’s needs. For example, the pharmacy may be compounding high-, medium-, or low-risk products. The periodicity and number of sampling locations may affect your decision. A high velocity volumetric impaction system is necessary to collect samples in an area with multiple and variable engineering controls (eg, a cleanroom environment with laminar flow in the room and/or 30 air exchanges per hour or multiple hoods with velocities anywhere from 55 cfm to 100 cfm). When different velocities are generated from the heating, ventilation and air conditioning systems, as well as the hoods and the sampler itself, the sampling process becomes inherently complicated. The volumetric sampler must have sufficient volume against the other velocities in the room or hood to pull the organism in.
Samples may be affected by additional factors, such as the cleaning agents and/ disinfectants used, the design and engineering controls in the room, or even the size of the organism itself. Organisms such as Staphylococcus spp., Bacillus spp., and Alternaria spp. have very different molecular weights. With organisms of different sizes and weights, the media in the sampler must be exactly the correct depth from the head to prevent an organism or spore from hitting the agar and bouncing off. The media also must be sufficiently moist so that the organism is not rendered nonviable upon impaction. If incorrect equipment or media is used during monitoring, it is likely that the laboratory data, as well as the interpretation of that data and the resultant conclusions, will be incorrect. Establishing any type of trend will be difficult.
Impaction samplers are available in a wide range of speeds and volumes as they are designed for myriad uses. The cleanroom is a relatively pristine environment with significant air exchanges, multiple and variable engineering controls, as well as a range of temperature and relative humidities; therefore, the volumetric air sampler should be able to collect a relatively large volume of samples at a reasonably high speed. For these purposes, the sampler should collect at 100 liters per minute at a minimum. We use a direct impaction volumetric sampler that collects 180 liters per minute and have found that to be very effective and reliable.
It is important to follow the United States Pharmacopeia (USP) guidelines for media use. Trypticase soy agar with polysorbate and lecithin (TSAp/l) is used for a variety of environmental testing. Fungal media, which can be either malt extract agar or yeast malt extract agar, is used in air sampling. The polysorbate and lecithin serve as a buffer and help to neutralize the effects of any alcohols and disinfectants, including phenolics, that may be collected with the source samples. Because alcohol and disinfectants are used throughout the compounding process, it is not uncommon for them to be aerosolized in the hood. For just this reason, you may want to consider using a fungal media that also contains polysorbate and lecithin, although this is not required by USP.
Avoid samplers with plastic parts and disposable heads. They do not offer as high a level of reproducibility as stainless steel and cast aluminum samplers. Also, disposable parts can get costly and plastics can serve as nutrition for “plasticizer” bacteria and fungi and also be difficult to sterilize. In addition, the volumetric air sampler must run independently, without cords. Choosing a battery-run product avoids the risk of bringing contamination into the cleanroom via the extension cord that has possibly been in a lot of dirty places. Again, any additional or external items have to be cleaned and periodically disinfected; follow the manufacturer’s recommended methods.
Finally, staff conducting any kind of environmental monitoring must be qualified—and in some states certified—to interpret the results and recognize when a problem exists, is developing, and what the problem is. Staff also must have some understanding of psychometrics (characteristics of water and moisture on the indoor environment) as well as some knowledge of the microbiology of the organisms isolated. This requires a solid understanding of the products being compounded, which engineering controls are in use, cleanroom workflow, and the interpretation, both clinical and environmental, of any positive microbiological results.
Support staff education and provide regular training in proper technique to ensure USP <797> compliance.
Staff members often confuse ISO validation testing conducted by the certifier with environmental testing. While ISO testing measures particle counts, its purpose is to measure the equipment’s ability to maintain a level of cleanliness to the ISO standard. Environmental monitoring, on the other hand, checks for organisms that are growing, have grown, or can continue to grow, survive, and create a reservoir that is not being controlled by the engineering controls or the HEPA filtration (for example, if there is a hole in the filter). Additional infection control concerns, such as contaminated ceiling tiles or water leaks in or near the IV pharmacy areas, create a safety hazard—or worse—affect patient care. Empower staff to report any concerns.
Too often we see staff collecting inappropriate volumes, collecting in a typically unused area, or using a vendor’s kit that was never intended to monitor the end product being tested. While pharmacy must develop a strong knowledge of USP <797> requirements, for pharmacy to simultaneously become experts in microbiology is certainly not feasible; therefore, it is key to take advantage of the expertise of microbiologists when establishing a monitoring protocol. This will ensure that the correct testing is performed by knowledgeable staff using the appropriate equipment to ensure accurate results.
Alice S. Weissfeld, PhD, D(ABMM), F(AAM), is the president, CEO, and laboratory director of Microbiology Specialists Incorporated, a reference laboratory she co-founded in 1984. She also serves as an adjunct assistant professor in the department of molecular virology and microbiology at Baylor College of Medicine. Alice earned her doctoral degree in microbiology at Rutgers University and completed a postdoctoral fellowship in public health and medical laboratory microbiology at Baylor College of Medicine. Her areas of expertise include virology, pathogenic bacteriology, mycobacteriology, administration, and regulatory affairs.
Paula H. Vance, RM/SM(NRCM), SM(ASCP), CIE(IAQA), is the vice president of Microbiology Specialists Incorporated. She is certified as a general supervisor in all subspecialty areas of clinical microbiology. Paula graduated from the University of Texas at Austin. She maintains certifications as a specialist microbiologist in public health and laboratory medicine, RM/SM(NRCM), a specialist in microbiology, SM(ASCP), and a certified indoor environmentalist, CIE(IAQA). Paula’s areas of expertise include mycology, mycobacteriology, and virology.
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