Q&A with Firouzan Massoomi, PharmD, FASHP,
Pharmacy Operations Coordinator,
Nebraska Methodist Hospital, Omaha
Pharmacy Purchasing & Products: How can outsourced environmental monitoring augment your in-house program?
Firouzan Massoomi: The primary issue within environmental monitoring is the consistent collection of the thorough information required to meet USP specifications. Sterile compounding is one of the most critical programs that pharmacy provides to our patients. We all understand the grave risks inherent in not following established standards when developing a thorough quality assurance program, as evidenced by the recent deaths and illnesses caused by contaminated compounded products. A good test is to put your sterile compounding team in the mindset of having to defend your program if an issue were to arise: Can you justify your program based on your processes for quality? By using a third-party vendor that provides expertise, and a continuous review of our processes, we can validate these processes.
Consider the radiation, oncology, and/or nuclear departments working with radioactive materials. They are held to high standards for radiation safety by both the state and the Nuclear Regulatory Commission (NRC). Biannual inspections verify whether the department is in compliance, and if not, the state agencies and NRC can shut it down. In addition, these departments must provide continuous documentation that radioactive agents are handled within established regulations. Unfortunately, <797> standards and inspections for sterile compounding are not held to the same high criteria, and they should be. Just as radiology cannot choose to be partially complaint with NRC regulations, pharmacy cannot choose to be partially compliant with <797>.
Given the high risk involved in this core pharmacy service, it is impossible to provide a 100% guarantee that there will never be an incident with a compounded product, but we can ensure that every possible safeguard is implemented to minimize risk points, and having a third-party vendor validate those processes and attest to the efficacy of the equipment should be part of that plan.
PP&P: How does outsourcing environmental monitoring impact USP <797> compliance efforts?
Massoomi: The purpose of USP <797> is to establish minimum standards for sterile compounding practice; the chapter is not intended to serve as a best practices document. To begin with, you need to ensure that, at a minimum, your practices consistently reflect these standards. As leaders, we have an inherent bias to assume our staff is doing things properly, which is why a third-party inspection is so valuable. Not only does a third party provide a fresh viewpoint, but their staff often comprises engineers and medical technicians, who bring additional expertise to the evaluation of your practices. It is impossible to overstate the value of verifying the compliance of your practice, and in my experience, a third-party vendor is perfectly suited to provide the checks and balances necessary to ensure full compliance.
PP&P: What criteria do you use to choose a vendor?
Massoomi: Reviewing the vendor’s sample environmental testing report will give you a clear understanding of how they operate. First, you are looking for a report that provides comprehensive information; you should not have to request additional data after reading the report. Look for a summary page that compares your facility’s test results to USP and other national standards such as International Organization for Standardization (ISO) standards for HEPA filter testing, American Society for Testing and Materials (ASTM) requirements for air particle counts, USP standards for room pressure, and Controlled Environment Testing Association (CETA) standards for laminar air flow hoods. Likewise, the report should be well organized and easy to read. Issues requiring action on your part should be clearly delineated.
The 45-page report our vendor provides twice a year describes all the tests they perform, the standards that each test is based on, the reason each test is performed, the areas tested, the certification of equipment used for testing, and the results (including the acceptance criteria for each result). The report is not simply perused and then filed away. Instead, we review the results as a team, noting any developing trends or process changes, and the resulting data serves to inform any necessary improvements to our practices.
To avoid complacency, we have reviewed multiple vendors over the past few years. Nonetheless, we have remained with our current vendor for the past 15 years due to their thorough processes, their depth of knowledge with regards to USP, ISO, CETA, and ASTM standards, and their overall relationship with vendors for laminar flow hoods, isolators, and HEPA filters. In addition, they have experience with various types of cleanrooms: negative pressure, positive pressure, open architecture, and closed architecture.
PP&P: In addition to reviewing a sample report, how else can pharmacy directors evaluate outsourced vendors?
Massoomi: It is important to verify the vendor’s expertise with not only USP <797> but with all standards surrounding sterile compounding; this is best accomplished by querying their approach to compliance testing. For example, ask how the vendor validates negative pressure in a cleanroom dedicated to hazardous compounding. It is also prudent to ask how the vendor alters their primary engineering control (PEC) tests depending on the manufacturer of the product in use. If the outsourced vendor does not have established policies and procedures (P&Ps) specific to your equipment, consider whether you want to serve as the test site, wherein the vendor investigates options, establishes procedures, and then tests and validates them at your expense.
Ultimately, I rely on the vendor to validate our processes. The cost of these services is less important to me than knowing that our compounding environments consistently follow the standards with the goal of delivering safe, sterile products to our patients. The definitive test of a vendor’s report is to ask: Should a patient incident occur, would you be confident presenting the document in court as a validation of your quality plan?
PP&P: Has your outsourcer identified any weaknesses in your procedures?
Massoomi: Each time they come in they identify new opportunities to improve our processes. Operational items our team performs on a day-to-day basis have been overlooked, and our vendor has been an excellent resource to ensure continuous compliance. For example, our latest report showed there were airborne bacteria in our anteroom that were not present in previous internal tests. To determine the source of the bacteria we brought the staff together to identify any practices that might have changed since the previous air sampling. One of the staff mentioned that a new cart had been brought into the anteroom and housed numerous medications the week before the latest inspection; we discovered that nobody had wiped the cart or the medications per our required standards. To remedy this, the cart and everything else in the room were wiped down, the vendor returned to resample, and the samples were clean. Although it is unknown whether this was the source, it was identified as a break in our standard of practice and required remediation.
Vendor reports should be read and examined carefully. We review the report (see sample page in Figure 1) in great detail to assess our progress in the previous six months. Pharmacy, engineering, and microbiology discuss each report, and determine where we have improved and where we failed to identify issues that we need to work on. Unfortunately, the state of Nebraska does not inspect for USP <797> compliance; thus, there are no state agencies to review our practices. Having a high-quality vendor that ensures we meet and exceed established standards gives us peace of mind.
PP&P: How do outsourcer inspections differ from those conducted by the state or other regulatory groups?
Massoomi: Nebraska state regulations do not mandate compliance with <797>; rather they defer accountability to federal regulations regarding <797>, so the enforcing agency is the FDA. Yet the FDA does not inspect hospitals for <797> compliance. Nebraska also does not recognize hospital pharmacy as a separate standard or group that needs to be inspected, so there is no state inspection of hospital pharmacies unless a health issue arises or a patient complaint is filed.
Unfortunately there are some people who may take advantage of this situation, but that is a an unacceptable practice mindset, and those individuals should not practice pharmacy. Because we average 650 compounded sterile products a day, I need my staff to be confident in our processes. They know that sterile compounding is one of our highest risk areas and as such requires the highest standards to ensure proper care of our patients. To that point, I leverage the biannual vendor inspection as if it were an inspection from the state or a Joint Commission review, in combination with continuous safety rounds with compounding personnel. Our goal is to ensure that our policies are technically correct and that our daily practice reflects our policies and meets the standards established by USP <797>.
PP&P: Is in-house testing still necessary if environmental monitoring is outsourced?
Massoomi: Yes, because the outsourcing report simply reflects a point in time every six months. We have partnered with our microbiology lab to help us develop a robust in-house program, including fingertip testing, air sampling, and swab testing. Fingertip testing is a part of our annual recertification, conducted at the beginning and during the compounding portion of the certification to identify gaps with standard operating procedures. We sample the rooms for airborne particle counts four times a year during the busiest compounding time. We swab high-use and high-risk areas, and our vendor swabs the same areas during their inspection.
There are other variables to test as well. For example, it is important to have pressure gauges in place to check the variances between rooms. Relying solely on a vendor to check the air pressures every six months leaves you with little understanding of what is going on day-to-day between rooms. Realizing this, we installed gauges and found that on a daily basis (and in some cases on almost an hourly basis), we were experiencing dramatic swings in air pressures between all the rooms; the rooms fluctuated from positive to negative pressure and back again multiple times during the day.
By <797> standards, a cleanroom always should be under positive pressure unless it is a designated negative pressure room for hazardous compounding. We worked with our engineers to remove the rooms from the main ventilation grid and reroute them so that they were not subject to building pressure variations. Now if the cleanroom veers toward negative pressure, we halt all compounding until the pressure returns to USP standards. Such room variations are not apparent if air pressure is checked only once every six months. We now have an internal checklist for monitoring room pressures, as well as temperature and humidity.
PP&P: Does it make sense to establish a dedicated staff position for ensuring <797> compliance?
Massoomi: Certainly each pharmacy director is ultimately responsible for overseeing the maintenance of USP <797> standards and ensuring the quality control components. However, in my experience I have found daily monitoring to be time consuming, particularly as the quality portion became more complex. To resolve this, I approached administration and received approval to reclassify a pharmacist as a sterile compounding specialist. We created a job description for a pharmacist whose role is to oversee and ensure the appropriate and safe compounding of all sterile pharmaceuticals for hospitalized and ambulatory patients, and trained this pharmacist to manage all our sterile compounding practices for both hazardous and non-hazardous drugs. This pharmacist liaises with our in-house microbiology department and our cleanroom vendors, and relies on our outsourced environmental monitoring vendor for additional support when necessary.
While our outsourced vendor inspects our facility twice a year, they are also available throughout the year if we have a concern with cleanroom operations or a sterility issue. On average, they are on site five times a year, in addition to the biannual inspections, in order to address situations such as malfunctioning laminar flow cabinets that require repair and retesting. At these times the benefit of a long-term relationship is obvious, as our vendor is familiar with our setup and understands our equipment. Given the depth of their experience with the various engineering control vendors, I rely on our vendor to order and install replacement parts when necessary, rather than assigning this task to the biomed department, as they have less experience with this equipment.
PP&P: What is the best approach for convincing administration to support the additional cost of outsourcing?
Massoomi: We simply estimated our costs for all the supplies and testing for each of our pharmacy team members in combination with the certifications for the rooms and equipment, and then budgeted for it annually. The pharmacy director needs to educate the administration that this is a cost of doing business. Sterile compounding is one of the core business lines pharmacy provides and given the inherent safety issues, this is not an area to skimp on to cut costs. Just as our facility would not choose to be compliant with only 50% of NRC regulations, we cannot choose to be only partially compliant with USP <797> in order to save money.
PP&P: What other reasons can you give pharmacy directors to consider outsourcing environmental monitoring?
Massoomi: Our profession exists to ensure safe medication practices for our patients. It is an unfortunate fact that patients get nosocomial infections in a hospital. The question to consider is whether pharmacy is contributing to patient infections. It is difficult to trace contamination to a single, patient-specific product; typically contamination is only identified when there is an outbreak from a large batch. Thus, it is imperative to have QC processes in place to minimize those risk points. Having a competent third-party vendor validating your environment and attesting to the equipment’s effectiveness is part of that process.
The easiest part of managing a cleanroom is the installation. Ensuring the continual safety and effectiveness of the cleanroom over time is where the challenge lies. As a living environment there is a long list of variables—people and products entering and exiting, changes in temperature and humidity, construction occurring within the building itself—that impact the cleanroom’s functioning. But the primary risk in any cleanroom is the variability introduced by staff members. It is the individual lapses that occur, like the new cart brought into the anteroom without first being wiped down, that generate potential contamination. Diligence is required to maintain a proper cleanroom environment, and that responsibility does not belong only to the pharmacy director or the sterile compounding specialist. It is vital that staff is educated as to the importance of being continually attentive to sterility, and ensuring that proper procedure is consistently followed.
The validation for that effort is the report from your external testing vendor that demonstrates your program’s effectiveness at assigned checkpoints. Without conducting sterility, stability, and concentration testing on every sterile compounded dose that leaves the pharmacy department, it is impossible to guarantee that every product is 100% safe. Hopefully, we are on the cusp of realizing robotic technology that can compound all sterile products in sealed cleanrooms without any human intervention, approaching a quality level wherein each product’s safety can be 100% guaranteed. But until that time, we must demonstrate that we are doing the best we can with the knowledge we have.
Firouzan “Fred” Massoomi, PharmD, FASHP, received his doctorate from the University of Kansas School of Pharmacy and is the pharmacy operations coordinator at the Nebraska Methodist Hospital in Omaha. He currently serves on the Nebraska Pharmacists Association Board of Directors.