Preparing for USP Chapter <800>: The Road to Remodeling

Corbin Bennett, PharmD MPH
Senior Director of Oncology and Outpatient Infusion Pharmacy Services
National Pharmacy Programs and Services
Kaiser Permanente
Fresno, CA

As the implementation date of U.S. Pharmacopeia General Chapter 800 (USP <800>), Hazardous Drugs—Handling in Healthcare Settings, quickly approaches, healthcare organizations are faced with challenges to ensure timely delivery of compliant clean rooms. USP <800> outlines facilities and engineering standards “to promote patient safety, worker safety, and environmental protection.” Pharmacy leaders must balance potential regulatory risk with cost when determining how and when to remodel existing clean rooms in order to meet USP <800> facilities standards. At Kaiser Permanente (KP), Pharmacy Services is closely collaborating with internal architects, engineers, and the finance department to remodel more than 100 sterile compounding pharmacies in nine states.

The Cost of Compliance
The initial USP <800> implementation date of July 1, 2018, was moved to December 1, 2019, in September 2017 to ensure alignment with the expected revision of USP Chapter <797>.¹ Prior to the delay, the National Alliance of State Pharmacy Associations (NASPA) released a chart outlining USP <800> adoption by state boards of pharmacy.² Only 14 states had adopted or planned to adopt USP <800> by the original implementation date of July 1, 2018. In most states a decision had been made not to enforce USP <800>, or discussions were just beginning. Despite the current general lack of state enforcement, the Joint Commission has begun enforcing elements of USP <800> related to facilities, including air-pressure differentials and primary engineering controls requirements.³

Some states may be reluctant to adopt USP <800> because of the potential high cost of upgrading sterile compounding facilities. This is understandable because costs to remodel to USP standards may total in the millions.⁴The average remodeling cost at KP is roughly $2 million per project, with some projects exceeding $3 million. Why the excessive cost? Three primary cost drivers are at work: space, location, and mechanical components.

Space is at a premium in all organizations. Many pharmacies built before the release of USP <800> lack a negative-pressure buffer room or dedicated receiving area. In the Kaiser Permanente National Template, a minimum of 170 square feet is suggested to ensure adequate room for equipment (biological safety cabinet, refrigerator, carts, etc.) in a negative-pressure buffer room to support a small-volume hazardous drug operation. Fifty square feet is the suggested size for a dedicated receiving area. This is in addition to the required positive-pressure room for nonhazardous drugs (110 sq. ft.), anteroom (170 sq. ft.), and nonclassified work space (250 sq. ft.). Kaiser Permanente hospital pharmacies are generally more expensive per square foot to remodel when compared to ambulatory outpatient clinics. This is primarily because of the limited options available in hospital space.

Location of the pharmacy is a significant cost driver. In many of our projects, bathrooms, exam rooms, offices, and other premium spaces have been sacrificed to carve out room for pharmacy expansion. This has a domino effect, causing other departments to be relocated, which in turn requires additional capital outlay to ensure operational harmony. Another aspect of the domino effect is the need for temporary space during the remodeling period. Temporary clean rooms built in a separate location and mobile clean rooms add to the cost of a project.

In a majority of KP projects, the phenomenon of trying to “fit a square peg in a round hole” also occurs, requiring unique solutions to meet compliance in less-than-ideal spaces. Pharmacy leaders need to begin crucial conversations now with the executive staff and other primary decision makers for space allocation. Healthcare leaders need to understand space and adjacency requirements up front. Organizations with “regulatory muscle,” such as those located in states or licensed spaces requiring compliance with USP <800>, may find it easier to procure adequate space. The delay in implementing USP <800> may have weakened this muscle in the short term, but pharmacy leaders understand that 18 months is a very tight timeline for procuring, designing, and constructing a new space.

Mechanical—or heating, ventilation, and air conditioning (HVAC)—design and construction is complex for even the simplest pharmacy remodel. But if your pharmacy is located in the basement of a multistory building, it becomes almost impossible. Mechanical upgrades in KP remodels are accounting for roughly 40 percent of the total cost. Discussions between pharmacy leadership and the design team are required to ensure clear understanding of the differences between the regulatory minimum and best practices. USP <800> requires the following: “Sterile and nonsterile HDs [hazardous drugs] must be compounded within a C-PEC [containment primary engineering control or hood] located in a C-SEC [containment secondary engineering control or buffer room]. The C-SEC used for sterile and nonsterile compounding must be externally vented, be physically separated (i.e., must be a room different from other preparation areas), have an appropriate air exchange (e.g., appropriate number of air changes per hour), and have a negative pressure between .01 and .03 inches of water column relative to all adjacent areas.”⁵ Organizations can meet these standards by using the biological safety cabinet (BSC) as the sole source of exhaust at a minimum. Although this is not stated in USP <800>, design consultants recommend a more elegant design using dedicated air-handling units with low exhausts built within the walls of the buffer room and also automated pressure controls with monitoring. The difference in capital outlay between the minimum and best-practice standard totals in the hundreds of thousands of dollars. However, in the long run the best practice ensures a cleaner space and may reduce the chance of failure in the environmental sampling program.

BSC selection is another cost driver. USP <800> requires that sterile compounding be done in a Class II Type A2, B1, or B2 BSC. Type A2 BSCs provide a portion of air that is recycled through a high-efficiency particulate air (HEPA) filter while exhausting the remaining air. Type B2 BSCs exhaust 100% of the air from the buffer room to the external environment.⁶ The difference in equipment cost of these two hoods is negligible. However, Type B2 BSCs require a complex design, making it difficult to maintain air balancing in the sterile compounding area. This leads to higher maintenance and energy costs for Type B2s. Type B2s are generally reserved for compounding volatile agents such as cyclophosphamide and fluoruracil.⁵ KP recently completed an internal study showing equivalent employee protection with the Type A2 and B2 BSCs when a volatile agent was being compounded. The KP standard for BSCs was changed to a Type A2 on the basis of these results.

Mobile Solutions
Mobile compounding trailers have created a significant buzz over the past year as a potential option for both temporary and permanent sterile compounding solutions. These units are self-contained, including buffer room, anteroom, and work rooms with compounding equipment (Type A2 hoods), all within a trailer on wheels. The small footprint allows for positioning on hospital or clinic property similar to mobile imaging units. Using mobile trailers may be a better option than remodeling a temporary space on the medical campus. However, pharmacy leaders must consider volume, regulatory requirements, and cost when evaluating the benefits of mobile trailers.

Mobile trailers can snugly accommodate two 3-foot hoods in each of the hazardous and nonhazardous buffer rooms, potentially allowing four technicians to compound at the same time. However, because of storage constraints, it is more likely that each buffer room will comfortably accommodate only one technician. The work area is small, making its use for document storage difficult. High-volume compounding pharmacies may be challenged to transition all sterile preparations to the mobile unit.

Regulatory requirements for mobile trailers vary by state. Some states allow for a “plug-and-play” model; compounding may commence after the trailers are parked and electricity and water have been connected. Other states require licensure prior to operation. California, for example, requires that mobile trailers be licensed by three regulatory bodies (Board of Pharmacy, California Department of Public Health, and the Office of Statewide Health Planning and Development).⁷ If the trailer is moved to a new location, even within the same medical campus, it must be relicensed. Licensure may take approximately 6 months from application submission to final inspection. This significantly limits the utility of mobile units as short-term solutions for pharmacies that require immediate support (i.e., pharmacies with positive environmental samples forced to cease compounding operations). The bottom line: it’s important to research your state’s regulatory requirements for licensing mobile trailers prior to purchase.

Cost must also be considered. Mobile compounding vendors offer both lease and purchase options. Lease options currently range from $25,000 to $30,000 per month with a 12-month minimum agreement. The cost to purchase may be nearly $1 million. If the mobile trailer will be used for more than 2 years, purchase may be the better option. In addition, some states may require registration with the Department of Motor Vehicles, which may add a significant cost.

KP has purchased one mobile trailer and leased two additional mobile trailers for temporary support of small- to medium-sized pharmacies. KP is still assessing the long-term potential for the purchased trailer at this time. The overall benefit of these mobile trailers remains to be seen.

Conclusion
The design and construction of clean rooms is a complex endeavor that requires thoughtful planning, significant capital, and careful timing. Pharmacy leaders are required to make a multitude of decisions during the process and must partner closely with facilities experts to ensure compliance while containing costs. Leaders must first assess the regulatory landscape and then engage organization leaders to identify space and capital. In addition, solutions for compounding during the construction period need to be identified; these may include mobile trailers and temporary compounding areas.

References

1. International Academy of Compounding Pharmacists. USP announces general chapter <800> implementation postponement to December 2019. September 29, 2017. http://www.iacprx.org/news/368148/USP-Announces-General-Chapter-800-Implementation-Postponement-to-December-2019.htm.
2. National Alliance of State Pharmacy Associations. USP 800 adoptions by state. August 17, 2017. https://naspa.us/2017/08/usp-800-adoptions-state/.
3. The Joint Commission. Prepublication Requirements. June 19, 2017. https://www.jointcommission.org/assets/1/18/PrePub_MC_OME_Final.pdf.
4. Beans BE. USP <800> adds significant safety standards. P T. 2017;42(5): 336-339.
5. USP Compounding Compendium 2017. Rockville, MD: United States Pharmacopeial Convention; 2017. USP <800> Hazardous Drugs—Handling in Healthcare Settings, Section 5.3.
6. USP Compounding Compendium 2017. Rockville, MD: United States Pharmacopeial Convention; 2017. USP <800> Hazardous Drugs—Handling in Healthcare Settings, Appendix 3.
7. Office of Statewide Health Planning and Development Facilities Development Division. Advisory Guide for Sterile Compounding Pharmacies. December 2017. https://www.oshpd.ca.gov/FDD/Training_Education/AdvisoryGuideA2-Pharmacy12072017.pdf.