When designing a new cleanroom—be it for USP compliance or to improve compounding efficiency—one of the first decisions is whether to install a modular design or the more traditional stick-built compounding facility. Because cleanroom construction has historically been stick-built, this continues to be the most common choice for new cleanroom installations, accounting for 85% of total cleanroom installation worldwide. The remaining 15% is the modular/prefabricated type.1 At first glance, standard off-the-shelf, prefabricated modular units may appear more cost-effective. However, once customization due to regulatory requirements comes into play, the total cost between the two methods may be similar. Also, bear in mind that due to economies of scale, the larger the room, the lower the cost per square foot. This article explores how the specific requirements of your project might drive your decision in either direction.

Decision Points

The first step is to decide which option—a traditional stick build, a modular build, or a hybrid of both—is the best fit for the organization. No one solution is better than another as each offers a variety of features; thus, the best fit ultimately depends on the individual needs of the facility.

There are a few key areas to consider before making a decision:

• If you are unfamiliar with modular cleanrooms, research different manufacturers to understand the design options, functionality, and regulatory compliance.
• Visit sites with stick-built cleanrooms and sites with modular cleanrooms.
• Obtain multiple quotes from modular manufacturers and cleanroom construction companies.
• Ensure operational functionality by communicating your design requirements and review how the construction team envisions your workflow.
• Analyze the overall cost differences between the two design options.

Each sterile compounding facility project presents unique design challenges. Nevertheless, there are some common considerations, including project budget, existing facility conditions, and the availability of skilled labor to perform the work. It is important to have a complete understanding of the different construction options before committing to a final design.

Traditional Stick-Built Compounding Facilities

Traditional stick-built construction with wallboard, such as gypsum or fiberglass composite, is field-fabricated and installed onsite. The build begins with the construction of the stud structure, which may be metal or wood. Wallboard is then attached to the studs and a joint compound is applied and smoothed by sanding. Finally, either several coats of epoxy paint are applied or a supplemental finished surface, such as polyvinyl chloride (PVCu) wall cladding, is installed. An acoustic ceiling is typical, consisting of an aluminum-grid frame with ceiling tiles of varying materials or epoxy-painted wallboard. There are both positive and negative attributes to this type of construction, which should be examined closely.

Traditional Stick Build Pros

• The construction costs can be spread over the time frame of the construction process versus incurring one large upfront cost.
• The construction materials (eg, studs and wallboard) used for traditional builds are quite common and thus typically cost-effective.
• Ordinarily, the necessary construction materials are readily available; however, the pandemic has delayed some material acquisition time frames.
• Contractors can usually accommodate field modifications and changes—both in the initial construction and in future mechanical, electrical, and plumbing (MEP) changes.
• There is a deep knowledge base for the means and methods of construction amongst many contractors.
• The facility has complete ownership of the build process.

Traditional Stick Build Cons

• Project quality will rely primarily on field construction rather than the factory-controlled conditions used for fabricating modular systems. The quality of the fabrication can vary due to human factors.
• While construction materials may be cheaper, time and construction management costs escalate the total price.
• Paper-based wallboard provides the necessary medium for fungal growth, such as mold, even if mold-resistant products are specified. However, the use of sealed, floor-to-ceiling wall cladding systems mitigate this risk.
• The sanding of the joint compound connecting the wallboard creates excessive particulate matter, which could transfer to sensitive areas.
• The harsh cleaning chemicals required for compounding facilities, such as sporicidal agents, can damage wallboard if proper precautions are not taken. The use of appropriate epoxy paint or wall cladding mitigates this risk.
• If there are construction delays, this can significantly impact pharmacy operations.
• Because the facility has complete ownership of the process, some may see this as a con, given the time commitment necessary to oversee the construction.
• Expansion of the current facility without going offline is nearly impossible.

Modular Compounding Facilities

The wall and ceiling systems for modular compounding facilities typically have a lightweight core composed of an aluminum honeycomb or foam inserted between galvanized steel or fiberglass outer sheets. The wall options are either glass panels that sit in aluminum frames or panel faces exposed to the compounding environment that are generally finished with a white, hygienic coating such as PVCu and are cold-welded together to create a monolithic, air-tight environment. Like stick-built cleanrooms, there are both advantages and disadvantages to this construction approach.

Modular Panel Pros

• Life-cycle costs are reduced with modular wall systems due to efficiencies gained in the cleaning process, such as elimination of the need to touch-up walls damaged by carts/equipment.
• Panels interlock during installation to create a closed environment with minimal air leakage/infiltration; thus, protecting the environment.
• Because field finishing is not required, no joint-compound sanding, priming, or painting is needed, which prevents the release of excess particulate and vapors in the facility.
• Walk-on ceiling systems allow for the creation of an interstitial space above the compounding areas, reducing shutdown requirements during regular maintenance by eliminating the need for ceiling access panels in ISO-classified rooms.
• Modular systems include cleanroom doors and hardware that are prepped for installation, which saves time.
• Because significant components are manufactured and assembled offsite, the construction and installation cycles are typically shortened, which reduces onsite intrusions and disruptions.
• Typical prefabricated modular units are freestanding and self-supporting with integrated HVAC and environmental systems.
• Cost savings can be realized in both labor and construction management.

Modular Panel Cons

• Supplied as a complete product, modular wall and ceiling systems typically require a significant upfront capital investment.
• The modular vendor may require the compounding facility provide a detailed spec document, which introduces an additional cost.
• Longer lead times are typically required for the build, as the required materials must be designed and fabricated.
• There is limited flexibility in conducting field modifications to modular panels. Onsite modifications may not be possible or may result in significant additional fees.
• If the optional walk-on ceiling system is chosen, the building structure must be substantial enough to support that load and there must be sufficient ceiling height to allow staff to stand and work in that space.
• Due to height restrictions incurred by current global building MEP infrastructure requirements, local building codes may make it difficult to retrofit into the existing space.
• Equipment customization may be limited due to the modular company’s contracts with equipment providers (for items such as HEPA filters, lighting fixtures, hand wash sinks, or pass-throughs). Ensure that all pre-contracted equipment is in line with best practices. For example, pass-throughs must be constructed of stainless steel, not plastic laminate over particle board, as this tends to chip over time and release particulates into the compounding area.

Review all applicable regulations with the manufacturer. Like stick-built construction, the modular units must meet local code requirements as well as USP and board of pharmacy requirements. To accomplish this, there are specific approaches that must be avoided in modular construction; for example:

• Avoid surfaces with ledges as this adds to cleaning time
• Exclude walls with a subtle pebbled texture, which does not meet the smooth-wall-surface requirement and can present cleaning challenges.
• Swinging doors are not appropriate, as they do not fully seal when closed.
• Ensure that the HEPA filters and fan filter units (FFUs) are connected to a dedicated HVAC supply without recirculation of the interstitial space above the ceiling, as this design provides for the best control of temperature and humidity.
• Avoid inappropriate airflow balance mechanisms such as transfer grilles in sterile compounding environments.

Hybrid Compounding Facilities

A third option is a blended or hybrid design that utilizes stick-built ceilings, sides, and flooring with modular frames and viewing windows or panels. These hybrid compounding facilities may decrease the costs associated with modular builds, particularly if the foundation already exists for the stick-built segments.

Ongoing Maintenance Costs

While initial construction and installation costs are primary concerns when building a cleanroom, another item to consider is the cost of maintaining and repairing the physical structure after installation. Both types of cleanroom designs—stick-built and modular—will require ongoing upkeep; neither option provides zero preventative maintenance.

It is important to establish who will be responsible for providing any required services post-construction. Traditional stick-built facilities will need preventative maintenance and damage mitigation. It is best practice to look to local contractors with cleanroom experience to manage repairs and maintenance. Due to its specialized nature, modular construction maintenance may need to be conducted by the primary installation company. When preventative maintenance and repair from damage or deterioration is limited to one company’s staff and materials, it may be more costly and not as readily available, leading to more downtime. Further, some replacement parts may be unavailable years down the road due to the age of the modular build.

Conclusion

Undertaking a cleanroom construction project can certainly seem daunting at the outset; however, there are many resources available to answer any questions that may arise throughout the process. It is quite likely that neighboring facilities have recently taken on similar installations and can serve as a font of information. State boards of pharmacy are an excellent resource for identifying issues that should be avoided. Finally, consider engaging with a consultant who is familiar with design, operational functionality, and regulatory compliance when building new compounding facilities. They often provide a unique, outside perspective and have direct experience with the challenges your pharmacy may face. Ultimately, it is pharmacy’s responsibility to ensure the selected company is familiar with USP <797> and USP <800> standards for 503A facilities, or FDA cGMP regulations for 503B facilities. Including your contractor in the design process and reviewing the construction documents prior to completion will provide the best outcome.

Mark Bodnar is the director of special projects for Kastango Consulting Group. He has over 40 years’ experience in sterile compounding, covering hospital, home infusion therapy, and LTC as well as FDA-regulated outsourcing facilities. Mark performs construction document reviews to ensure regulatory compliance and recommends best practices for sterile compounding facilities. He is also a peer reviewer for gap analysis, facility design development, and other related documents.

References

1. Rader RA. The next decade of cleanrooms. Pharma Manufacturing. www.pharmamanufacturing.com/articles/2019/the-next-decade-of-cleanrooms. Accessed October 1, 2021.
2. Manohar R. Following standards while designing clean rooms ensures mutual benefits for makers and buyers. Beroe. www.beroeinc.com/whitepaper/clean-rooms. Accessed October 1, 2021.