When considering how to approach a new cleanroom construction project or the renovation of an existing facility, there are several key factors that will influence the design. These factors include operations, equipment, workflow, safety, quality, and more. Careful attention to these subjects helps demonstrate a facility's ongoing commitment to staff and patient safety. However, there is another key component that is often overlooked during clean room design. Environmental monitoring (EM) should be a key element when designing a cleanroom construction or renovation. Frequently, EM can be an afterthought and is only paid attention to when issues arise with results during the testing and acceptance phases of construction. This article reviews the key items that the pharmacy cleanroom manager, cleanroom consultant, architect, design team, MEP (mechanical, electrical, and plumbing) consultant, and facilities team should consider for a successful EM program at the conclusion of construction and beyond.
EM testing is a requirement of USP compounding standards and for facilities operating under FDA current Good Manufacturing Practice (cGMP) regulations. With a robust EM program, a facility can demonstrate that they are meeting the minimum compounding standards and are operating under a state of control. By monitoring air and surfaces for viable and total airborne particle counts, the facility can assess whether proper personnel practices are being followed, cleaning and disinfecting agents are effective, environmental quality is maintained, and ensure the engineering controls are performing properly. During the design phases of cleanroom renovation projects, special consideration should be taken to assess the layout, finishes, and selection of engineering controls and heating, ventilation, and air conditioning (HVAC) systems to ensure they will allow the facility to operate under a state of control.
The cleanroom construction journey begins with the design. Often, facilities collaborate with an architect and a cleanroom design consultant to optimize the design. It is important to recognize that both the design and layout of the facility have a direct impact on the success of the future EM program. For example, consider two activities that generate significant particles and aerosols: garbing and hand hygiene. Simply moving the arms, legs, or head can generate particles, while performing hand hygiene can cause splashing which can release further aerosols into the air. These two activities, coupled with the placement of the sink and the layout of the anteroom in conjunction with the other classified spaces, will have a significant impact on the success of the future EM program.
The 2021 draft of USP <797> allows for physically separated dirty (ie, wet) and clean (ie, dry) anterooms.1 This separation of the particle generating activities, especially in a cleanroom suite with a negative pressure hazardous drug (HD) buffer room, may have significant impacts on preventing the ingress of particles and aerosols through the offset balancing airflow into the negatively pressured HD buffer room. One design solution is the physical separation of the ISO 8 wet anteroom where garbing and hand hygiene occur from the negatively pressured ISO 7 sterile HD compounding space with the addition of a sterile dry ISO 7 anteroom (See FIGURE). With this approach, activities in the dry anteroom should be kept to a minimum.
Modular vs Stick-Built Construction
Another key decision is whether to utilize a modular cleanroom vendor or pursue stick-built construction with a local general contractor. The November 2021 PP&P article “Choosing the Right Cleanroom Construction Approach” outlines the pros and cons of these two construction approaches.2 A modular vendor usually has extensive experience building classified spaces and fabricates the modular portions in a highly controlled environment, whereas a local vendor hired for a stick build may not have a similar depth of experience with classified spaces. There are also EM impacts to weigh as part of this choice. With modular construction, be cautious to ensure the design minimizes or eliminates dust collecting ledges. For stick builds, the primary concern is preventing the dirt and debris that are generated during construction leading to future environmental contamination issues.
Cleanroom Air Changes
The impact of compounding volume, the number of personnel, and cleanroom activity levels can drastically affect EM considerations. Discuss these variables during the design phase with the mechanical engineering team, commissioning team, and the cleanroom design consultant to better understand how they will impact future EM. High volume facilities may require additional high efficiency particulate air (HEPA) filtered air changes per hour (ACPH) to maintain ISO Class 7 air under dynamic conditions. A 1000 bed facility that is compounding an average of 800 doses per day with 5 or 6 technicians in the cleanroom at a time will have different design needs than a small community hospital with a single PEC with a lower volume of CSPs performing only occasional HD compounding in the HD space. Furthermore, when considering personnel load in ISO classified spaces, look at not only the number of pharmacists and technicians, but also consider trainees and the certifying vendor that comes in to take samples. Remember that USP ACPH levels are minimum standards, and there should always be flexibility in your ACPH.
Understanding the type of exhaust fans used for negative pressure rooms is also important for the overall design. The pros and cons of belt drive vs direct drive need to be considered by the MEP team. Belt driven systems require significant preventative maintenance on the part of the facilities department as the belts must be exchanged or adjusted every 3 months. Recertification should occur after each belt adjustment. Direct drive exhaust fans may be more appropriate as they require less maintenance. Consider storing backup equipment on-site may to allow for quick replacement should an issue arise.
HVAC design considerations are a cornerstone to the success of a program’s EM. First, the engineering and commissioning teams need to assess the capacity of existing systems and consider whether additional HVAC modifications are necessary to achieve cooling and air change requirements. Additionally, the HVAC systems should be designed with a safety factor of at least 20% beyond the minimum ACPH and at least 5% below the maximum allowable temperature and relative humidity. If the system is designed only to meet the minimum standard, you will drift out of compliance very quickly. For example, if the ACPH in a buffer room are designed to the minimum of 30 ACPH, the space will likely be almost immediately out of compliance due to HEPA filter loading. In addition to ACPH, the facility’s temperature requirements must also be considered. USP’s minimum standards for temperature are also a recommendation. As such, it is critical to determine what standards are necessary for your particular space. The number of staff, equipment, and type of PPE worn inside the room should be used to guide the decision-making. For example, if staff is expected to wear full coveralls and a polypropylene coated chemotherapy gown for the entire day, the USP temperature recommendation is going to be too warm.
Do not overlook the importance of designing precautionary safeguards for your cooling system and chillers. These safeguards will vary depending on geographical location and climate (eg, Colorado vs Florida). Consider a situation wherein a very cold room (eg, 62°F) gets a burst of 90°F air into the space due to the building chillers being down; this will cause significant moisture and condensation within the cleanroom. One option is to design the system to ensure the air handlers will shut down if the cooled water system goes above a certain temperature. Of course, this needs to include operational considerations for next steps once the air handlers are turned off.
The selection of architectural finishes and any additional items that will be placed into the ISO classified spaces all have a considerable impact on future EM program success (see TABLE 1). See the July 2019 PP&P article, “Designing the Pharmacy Cleanroom of the Future” for design element considerations throughout the cleanroom design process.3 An important element to carefully consider is the selection of the sink, which should be stainless steel and have a deep scrub basin to minimize splashing and the generation of aerosols. Examples of this are scrub sinks that provide adequate space for staff to ensure proper hand hygiene technique and have a built in eye station (see PHOTO 3). A low wall return should be placed near the sink on the side farthest from the entrance of the ISO 7 classified spaces to pull aerosols and particles away from the entrance to the buffer room or ISO 7 classified dry anteroom.
When preparing to embark on construction, the construction project manager needs to have a keen understanding of the differences in building a pharmacy space as opposed to other construction projects in a hospital facility. This individual is responsible for overseeing the coordination of work among the various vendors and must also ensure there is a clean construction protocol (CCP) in place throughout the construction phase. Clean construction is the practice of employing clean construction methods and processes to prevent excessive non-viable and viable particles from being introduced into and left behind in the facility as it is constructed.
Throughout the project, various clean construction stages should be established within the construction schedule in which cleaning requirements for the project become more stringent, and the type and methods of work become more restrictive. The CCP includes establishing a controlled access entrance, required actions for equipment delivery (such as establishing an equipment wipe down area), specification of sporicidal and disinfecting agents used to wipe down all equipment, and garbing procedures specific to each of the four clean stages. The CCP stages are:
Another important role during construction is the construction quality control manager (CQC). This role can be designated by the contractor, pharmacy director, or the cleanroom consultant. The oversight of construction quality assurance throughout the entirety of the project by an appointed CQC manager ensures the correct materials and finishes are chosen, those materials are properly installed, and the CCP is followed consistently. The importance of proper material selection is exemplified in ceiling and drywall choices; typically, hard ceilings are preferred; however, if using ceiling tiles, they must be cleanroom grade and the silicone caulking used must be mold-, mildew-, and moisture-resistant. The improper selection of materials, such as paperfacing drywall, can become an excellent food source for mold. The contractor and CQC manager must also understand the impact of improperly applied materials. For example, if epoxy paint is used, improper application without the proper cure time between coats can lead to peeling, chipping, and EM failures. In addition, unsealed ceiling tiles and unsealed electrical outlets in a negative pressure space will constantly pull in contaminants, which can cause EM failures.
Avoid Construction Traps
There are several issues that are easy to overlook during cleanroom construction, but have simple solutions:
Cleanroom design and construction are complex undertakings that require expertise from multiple stakeholders. It is critical that pharmacy be at the table and participate in the decision-making throughout the process. To ensure a successful ongoing EM program, EM principles must be incorporated into the design process at the outset of the project. Pharmacy leaders should invest time upfront in understanding the potential pitfalls of their cleanroom program’s proposed design and its impact on EM. It is equally important to keep EM in mind during the cleanroom construction process. Partner with a vendor that appreciates the importance of clean construction and construction quality control in a cleanroom project. Given the variability of expertise among vendors, subcontractors, architects, and engineers, a qualified and experienced cleanroom consultant can provide value by leveraging past experiences and applying best practices. Ultimately, pharmacy leadership is responsible for the ongoing cleanroom certification and EM, therefore having a strong understanding of the design is crucial for long-term EM success.
Elaine Strauss, PharmD, MS, BCSCP serves as the senior consultant for cleanrooms and sterile compounding at WorkingBuildings, a Trinity Consultants Company. She received her doctor of pharmacy degree in 2010 from the University of Georgia and a master of science in health system pharmacy administration from the University of Pittsburgh in 2012. In 2021, Dr. Strauss achieved Board Certification as a sterile compounding pharmacist.
Lilit Smith, PharmD, MBA, BCSCP serves as the manager for compounding and compliance at Baptist Health South Florida. She received her doctor of pharmacy degree in 2007 and master of business administration in 2015 from the University of Connecticut. In 2019, Dr. Smith achieved Board Certification as a sterile compounding pharmacist.