Pharmacy Purchasing & Products: What value does environmental monitoring bring to pharmacy’s compounding operation?

Fran McAteer: When USP Chapter was first released, many pharmacists viewed environmental monitoring as another financial burden that could be mitigated by employing an outside consultant or laboratory. However, over the last year or two most have realized the positive impact of on their entire IV quality system. The reality is that the statutes on environmental monitoring provide a quality feedback process for the entire CSP program. Closely following the guidelines provides a precise measure of how personnel are performing, whether equipment is working properly, and whether facilities are properly designed and engineered. These measurements can then help determine whether cleaning and sanitization procedures are adequate, or whether technicians’ techniques are aseptic.

PP&P: What microbiology issues does a pharmacist need to be informed of regarding environmental monitoring?

FM: While pharmacists certainly understand environmental monitoring techniques, it is important to recognize the impact the pharmacy environment can have on contamination levels. A properly designed cleanroom provides constant air filtering, pressure differentials, and air velocity, for example—all which help prevent bacteria and microorganisms from creating contamination in the workspace.

Never underestimate the ability of contamination to be introduced and to spread due to improper aseptic technique. This applies to more than just the actual cleanroom. Proper technique should always be used when compounding and storing IVs. Frequent training of personnel in the practice of donning PPE, disinfecting biological safety cabinets, and practicing good hand hygiene is essential to ensuring compliance.

PP&P: How serious is the risk of contamination for products compounded in the pharmacy?

FM: It is important to realize that if contamination exists in the compounding area, there is a tremendous risk of transferring it directly to the patient population via intravenous medications. In the case of a contaminated drug from a manufacturer, the product can be recalled rather quickly due to the network of distributors and wholesalers that serve as a buffer for the hospital and, ultimately, the patient. A hospital, however, has little in the way of a buffer zone between the pharmacy compounding area and the patient, making contamination a major area of concern.

To address this risk, a cleanroom must be cleaned, sanitized, and disinfected frequently in order to maintain aseptic conditions. Personnel working in the cleanroom need a schedule of continual training on proper aseptic technique, as well as reinforcement of the proper use of PPE and how to enter and exit the cleanroom. One of the challenging elements of is ongoing and persistent enforcement of proper garbing, hand hygiene, and disinfection of staff.

PP&P: What are good approaches to educating pharmacists on preventing contamination?

FM: It is important for all pharmacy staff to understand the science behind the techniques they are employing. Didactic training programs—whether they are live, online, or written programs—are all good sources for this. As consultants, we always couple our environmental monitoring programs with staff educational seminars on topics such as cleanroom basics, sterile compounding, and requirements of USP . These in-service programs cover topics such as the impact personnel can have on the environment, the factors that go into cleanroom design, basic microbiology concepts, how contamination can spread through normal activities, how PPE should be donned and used in a cleanroom, and principles of disinfection. We then immediately follow up these educational programs with individual media fill testing to ensure proper aseptic technique for IV preparation is being followed; a particle counter is inserted in the compounding area so the technician can see how increased particle generation is directly linked to contamination risk. After observation and discussion, we do glove-fingertip samples on the technicians to emphasize the importance of disinfection.

The strategy is to introduce the pharmacy staff to the appropriate level of education and hands-on training before initiating the environmental monitoring program. When pharmacy staff understands the principles behind avoiding contamination, the risk can be minimized at the onset. All of these steps lead to consistent prevention of contamination.

PP&P: How can the risk of false positives/negatives be avoided?

FM: Bad sampling techniques can result in many problems. When there is a spike in positive results, it is important to review whether there have been any recent changes in compounding procedures, equipment, materials, and/or personnel. We have actually seen spikes in positive results with colonies forming on the outside edges of sampling plates when there is a new pharmacist overseeing the compounding technicians. This is caused not by the compounding technician, but rather by the new pharmacist not using proper aseptic technique when handing the plates to, or collecting them from, the technicians.

It is important to remember that environmental monitoring is a dynamic process that is meant to provide realistic feedback on contamination levels present during your IV medication compounding. It is imperative that staff understands this concept so they do not engage in practices that are likely to result in false negatives, leaving patients at increased risk for receiving contaminated products. For example, when fingertip testing is initiated, we have seen staff spraying their hands immediately prior to the testing with isopropyl alcohol (IPA), thus producing a false negative. When analyzing environmental monitoring trends, numerous false positives or false negatives will give the wrong impression. False negatives are particularly disconcerting as they will lead pharmacy management to think there is no contamination at their facility, while it may simply mean staff are either wiping surfaces or spraying fingertips with IPA prior to testing, ensuring zero growth and not demonstrating actual conditions.

PP&P: What are the types of conditions that can adversely affect an environmental sample?

FM: An environmental sample can contain living organisms, so many different factors can affect it. This underscores the need for sampling to be done under aseptic conditions. Whether this is done in-house or outsourced, specialized training is necessary for those who are doing the sampling.

Aseptic conditions also should be in place when transporting sampling plates to the incubator. If plates are transported in a bag, the bag should be sterile. If the plates are dropped on the floor, they should be discarded and the sample retaken. If samples are transported to an outside facility, outside temperature conditions (i.e., higher than average heat or cold) can cause condensation to appear on the media and ruin the sample.

PP&P: How should pharmacy approach glove fingertip sampling?

FM: Glove fingertip sampling is a good monitoring technique that provides dynamic feedback by supplying measurements of contamination at the fingertip level—the tactile manipulation point of the technician compounding an IV medication. This type of monitoring can yield significant data points as any contamination on the fingertip can easily be transferred into an IV medication. It is always important for those conducting testing to stress that no IPA or ethanol should be used prior to performing a sampling, as this will lead to a false negative.

Another effective method is to tie sampling to a media proficiency test. After a technician or pharmacist does a media proficiency test, they should perform a right and left fingertip test, thereby gauging media proficiency for their whole compound plus their fingertips. This practice can reinforce good technique by associating fingertip testing with contamination and media proficiency.

You should also keep in mind that whoever is performing the sampling should be well trained in aseptic technique to avoid introducing a false positive scenario into fingertip testing, which can incorrectly influence a recall of products.

PP&P: What trending data should pharmacy be particularly aware of when reviewing environmental monitoring reports?

FM: If you find increased particle counts on the non-viable monitoring side (usually indicative of more dust in the air) those increases are often directly proportional to bacterial contamination. For example, if you sample your ISO Class 100 laminar flow hood—which should normally display less than 100 0.5 micro particles—and you start seeing increases up to the 50s or 60s or counts over 100, you may have an engineering issue where the HEPA filter is damaged or the pre-filter is clogged, indicating to management that maintenance is needed. If there is a trend of increasing contamination levels over time, it may signal that a action level for surface and/or air contamination may be triggered; this should be followed by an investigation that includes resanitization and retesting. Higher bacterial level trends may indicate  that  cleaning and disinfection is not adequate and needs to be more frequent, or it could signal an influx of new technicians being trained or perhaps increased particle contamination from dust due to son-going construction in or around the hospital pharmacy area. The key is to pinpoint where trends are starting to increase and then be proactive with training, education, or corrective action programs and enforcement scenarios.

PP&P: When does it make sense for a hospital’s microbiology lab to conduct the monitoring as opposed to the hospital pharmacy?

FM: Making this kind of determination can be difficult. A hospital microbiology lab is a clinical laboratory that is set up for mostly automated techniques. Pharmaceutical microbiology for cleanroom and IV testing is different than clinical microbiology in that there are different types of bacteria in the pharmacy and different techniques needed to measure and isolate them. Methods such as USP Sterility Testing and USP Bacterial Endotoxin Testing are formal, recognized procedures for testing CSPs. The techniques and incubation temperatures required are often unique to testing of the cleanroom and not used by the hospital’s clinical microbiology lab. Environmental monitoring is used to looking for very low levels of contaminants in the sterile products pharmacy operation. When using a modern cleanroom with a high level of air filtration (e.g., an ISO Class 7 with 150 room changes per hour), there are not a lot of organisms that can grow and survive in that type of environment, but the ones that do are of particular concern, as they are showing resistance to cleanroom design and the frequent disinfection process. So, in pharmaceutical microbiology we are looking for low levels of contaminants, generally less then 100 CFUs (colony forming units) per plate. Media used in environmental monitoring such as TSA (trypticase soy agar), used in both air and surface monitoring, is typically qualified before use to demonstrate growth promotion of low levels of organisms (10 to 100 CFUs). This is opposed to a clinical setting where blood, urine, or other types of body fluid samples are analyzed for different pathogenic organisms with much higher counts. So, in pharmacy the approach to environmental monitoring is different and may not be within the expertise of the hospital clinical microbiology lab.

The two governing sections of USP relating to environmental monitoring are Chapter Pharmaceutical Compounding—Sterile Preparations and Chapter Microbiological Evaluation of Clean Rooms and Other Controlled Environments. Whereas focuses on sterile compounding, covers specific microbiological evaluations of cleanroom and control design. You want to make sure your hospital microbiology lab has this expertise and can allot the necessary FTEs to conduct the monitoring in a timely fashion.

PP&P: Is there an argument against pharmacy using their own incubators for environmental monitoring?

FM: There are certainly qualitative measures that must be taken into account when deciding which incubators to use. Environmental monitoring, as defined by USP and , is based on specific incubation temperatures and duration. It is not uncommon to find incubators in the pharmacy that have not been calibrated, usually indicating that they have not been held to National Institute of Standards and Technology (NIST) standards and therefore have not been proven to maintain the appropriate temperature. Generally, incubators should be calibrated on an annual basis. If an incubator’s temperature is running too low or too high, it will impact environmental monitoring results.

In addition to being calibrated to maintain overall temperature, most microbiology lab incubators also are validated to ensure the designated temperature can be maintained for a period of 24 hours with both full and empty loads. This involves thermocouple measurements for each shelf, as temperature specifications within a pharmaceutical microbiology lab are precise. Lastly, pharmacy incubators often are not cleaned and sanitized on a regular basis. Incubators are prone to mold contamination—especially if standing water is present.  Obviously, when measuring contamination levels of samples in a contaminated incubator, the results will be inaccurate.

PP&P: When do you recommend pharmacy consider using outsourced services for environmental monitoring processes?

FM: Outsourcing generally makes sense, although we do have clients that prefer to perform their monitoring processes in-house and leave the analysis, training, and trending to us. Consider the time commitment required to develop a sufficient expertise in microbiology. This requires building an in-depth knowledge of the appropriate procedures and applicable compliance statutes, as well as how to procure the proper equipment. It may make more sense for pharmacy to outsource their environmental monitoring rather than impede on pharmacists’ patient care expertise by making them, in effect, microbiologists. While an in-house process may be cost effective for some institutions, factor in the cost of training as well as the financial impact of taking a pharmacist away from his or her other duties when comparing the cost of an in-house process against an outsourced one.
 

Fran McAteer, MS, MBA, is vice president of quality at Microbiology Research Associates, Inc, an FDA-registered contract microbiology testing laboratory specializing in USP testing for pharmaceuticals, biologics, and medical devices. Fran has expertise and experience in the implementation of USP programs for hospital pharmacies and acts as a consultant for many hospitals.