Since the tragedy that came to light in October 2012, when contaminated epidural steroid injections produced by NECC caused significant patient harm, including the deaths of 64 people, there has been a strong focus by the FDA and local state boards of pharmacy on ensuring strict regulatory compliance during sterile compounding. A likely contributory factor to the contamination appears to be the general disrepair of NECC’s physical plant and a lack of proper upkeep of the cleanrooms themselves, concerns that have received extensive government and media attention.¹ In 2012, the FDA issued 47 Form 483s involving procedures for sterile drug products; in 2013, the number of Form 483s issued to pharmacies detailing objectionable conditions concerning procedures for sterile drug products that required correction surged to 76.^2,3 

With this renewed zeal behind regulatory efforts, cleanrooms themselves have become the central focus of many inspections; however, it is important to note that a compliantly constructed cleanroom also requires the establishment of comprehensive policies and procedures (P&Ps) and an all-inclusive, competency-based compounder training program to exert the proper control over compounding operations. A properly designed, constructed, installed, and maintained cleanroom is not the sole factor in a fully compliant USP <797> sterile preparations compounding program; nonetheless, it is the largest and most visible component. Maintaining a compliant cleanroom is essential to ensuring that regulatory bodies have a high level of confidence in your compounding program. 

When planning a reinvestment in the physical plant, a well-designed strategy and a complete project checklist are essential to ensure success. (See Sample Cleanroom Construction Checklist Excerpt below.) Developing a complete plan before embarking on construction will keep your team focused on the ultimate objective of the project—building a <797>-compliant cleanroom that effectively supports pharmacy workflow—and will help you stay within budget and avoid the major roadblocks that can derail any renovation project.

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Develop a Project Checklist
Create a list of desired elements for the new or renovated cleanroom and assign them to one of two categories: the essentials (elements that are critical to the basic functioning of the cleanroom complex, mandated by regulation, or central to the efficient functioning of the operation), or ancillary items (components that would be nice to have but are not crucial to ensure functionality or compliance). The essential items are outlined in the Facility Design and Environmental Controls section of USP General Chapter <797>: 

• Basic Cleanroom Structure. Determine whether the cleanroom will be modular construction or traditional drywall construction (ie, stick built). Then, evaluate the available options and select the fit and finishes of the cleanroom, including ceilings, floors, walls, doors, and light fixtures. 
• Safety Systems. Choose flush-mounted sprinkler heads, emergency lights, eye wash fixtures, and any other life-safety elements as mandated by local code. 
• Secondary Engineering Controls (SECs). To control your cleanroom complex within acceptable limits and approved tolerances for temperature, humidity, and airflow, a properly sized and maintained HVAC and HEPA air filtration system is vital. The Controlled Environment Testing Association (CETA)4 and USP <797> provide broad guidance on SECs.
• Primary Engineering Controls (PECs). Select effective laminar flow cabinets, workbenches, biological safety cabinets, and/or isolator units for compounding. 

In addition, consider taking an open architecture approach to cleanroom builds, which can include integrated, unidirectional vertical laminar flow (UVLF) workbenches (see Open Architecture Design Considerations in the Cleanroom in PP&P’s May 2014 issue).

Ancillary elements in a cleanroom build or renovation project may include new and innovative technologies:

• Telepharmacy systems with camera or video capture systems
• Automated continuous environmental monitoring systems
• Automated compounding devices or other robotics

Other non-essential, but possibly valuable additions to your cleanroom may include:

• Powered door openers
• Cleanroom seating
• Large view windows
• Pass-through cabinets, pass-through refrigerators, or full-height pass-throughs for transferring drugs, supplies, and other materials into and out of the cleanroom

A qualified cleanroom consultant can assist in evaluating the myriad choices available and can provide insight into what has worked—and more importantly, what has not worked—in installations at similar facilities. In addition to providing guidance on technical and regulatory issues, an experienced consultant can advocate on your behalf with both the cleanroom contractor and your organization’s administration for elements that are required to ensure the long-term success of your operation. Even if your team already includes an architect and general contractor, a consultant with pharmacy experience in cleanroom workflow and design, budget processes, and assembly of these complex rooms can aid in ensuring a smooth process. 

Managing the Construction Timeline

After approval of the project is granted by administration (see Design Your Cleanroom to Ensure Easier Use, Cleaning, and Maintenance from PP&P’s March 2006 issue for tips on gaining administrative buy-in), and alteration of this state-registered space is granted by the appropriate regulatory authority (state board of pharmacy or local health department), effective coordination of the cleanroom builder and other associated trades (eg, plumbing, electrical, fire suppression, etc) is essential. An organization’s internal resources—a qualified maintenance engineer, plant operations personnel, or an experienced pharmacist assigned to the project—may coordinate the project; however, a qualified general contractor or cleanroom consultant may have more experience in pharmacy renovation. Some regulatory authorities require a written transition plan that delineates where and how services will be provided during the construction phase.

Ideally, a suitable temporary cleanroom location is designated, and proper primary and secondary engineering controls established before the primary compounding room(s) is disabled. Another strategy is to temporarily transfer compounding to satellite areas. The short-term lease of containment technology (ie, isolators) may be another suitable alternative. Finally, if approved by the hospital’s P&T committee, temporarily employing an offsite contract compounder or outsourcing vendor may assist in the short term to reduce workloads and compounding volumes during the construction process. Compounding at the patient bedside and the overuse of the immediate-use exemption within USP <797> should be avoided—these practices are potentially perilous and violate many TJC standards and local regulatory statutes. 

All options should be thoroughly discussed and the agreed upon plan communicated to all disciplines within the organization. 

Determine the Size and Composition of the Cleanroom

When planning a cleanroom renovation, it is essential to determine how much space will be required to ensure workflow efficiency, as well as to identify the ideal materials to ensure longevity of the investment. Key questions to ask include:

• Is the existing space sufficient for current operations (both compounding areas and the surrounding supportive areas)?
• Does the current compounding space support an ideal workflow? If not, how can it be improved?
• Is a significant increase in compounding volume expected in the future? 
• Does the current space have both hazardous and non-hazardous compounding areas required (ie, positive and negative pressure spaces as needed)?

To maximize the available space, careful consideration should be paid to the type of construction materials utilized. The higher costs of a modular room made with aluminum composite materials (ACM) or other durable panel materials may be offset by the daily labor-time savings realized, because these rooms are typically easy to clean since their joints and finishes have been designed for that purpose. Consider both durability and aesthetics when choosing components. Your staff will appreciate efforts to create a pleasing work environment. In addition, ease of assembly is important during the construction phase; components that are pre-fabricated offsite can result in a more efficient installation. 
Although most state boards allow traditional drywall construction with epoxy-coated, water-based paint finishes, and oil-based epoxy paint is no longer available, use of water-based epoxy paints tends not to stand up to repeated cleanings and sanitization cycles as well as oil-based epoxy paint. This necessitates increased maintenance of the cleanrooms and could affect their usable lifespan. In addition, choosing mobile carts and racks rather than built-in shelving and other static casework may be prudent:

• Mobile racks can be continually reconfigured within the space to accommodate changing workflow, even on a shift-to-shift basis as the nature of compounding changes.
• Mobile racks are cost-effective and easily replaced if worn or damaged.
• Movable racks permit quick and thorough cleaning.
• Since these items are not tethered to the walls or flooring, air flow within the space is efficient.

When considering mobile storage solutions for the cleanroom, be sure they are cleanroom grade and constructed of acceptable materials, such as stainless steel, composites, and aluminum.

Summary
Committing to a rehabilitation of a critical space, such as a cleanroom, must be undertaken with the forethought such a project deserves. A detailed project plan and complete checklist of items and activities required is essential for a successful redesign and build project. Involving qualified, knowledgeable, and experienced professionals may assist in keeping the project on track, within budget, and in line with the business plan. Close adherence to the project plan and checklist will ease the burden on compounding leadership in their efforts to keep their team apprised of progress, ensure service providers are accountable for their areas of expertise, and provide peace of mind during a challenging renovation project. 

References

1. New England Compounding Center (NECC) Preliminary Investigation Findings, 10.23.12 – The Commonwealth of Massachusetts Executive Office of Health and Human Services (Massachusetts Department of Public Health). http://www.mass.gov/eohhs/docs/dph/quality/boards/necc/necc-preliminary-report-10-23-2012.pdf. Accessed June 9, 2014.
2. US Department of Health & Human Services. US Food and Drug Administration. Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letters. http://www.fda.gov/iceci/enforcementactions/warningletters/default.htm. Accessed June 23, 2014. 
3. US Department of Health & Human Services. US Food and Drug Administration. Drugs: Registered Outsourcing Facilities. http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/pharmacycompounding/ucm378645.htm. Accessed June 23, 2014.
4. Controlled Environment Testing Association (CETA) Web site. www.CETAinternational.org. Accessed June 11, 2014.

Lou Diorio, RPh, FAPhA, is a principal of LDT Health Solutions, Inc, a medication safety and quality management consulting company. Lou is a graduate of Long Island University’s Schwartz College of Pharmacy, where he is also an adjunct professor of pharmacy practice, a member of the college’s Alumni Board, and preceptor of pharmacy students.

David Thomas, RPh, MBA, is a principal of LDT Health Solutions, having previously served as the director of information technology operations for SoluNet, LLC. In addition, Dave served as a manager of implementation and technology development for Baxter Healthcare. Prior to his 15-year tenure with Baxter, Dave held hospital practice and management positions for five years. He is a graduate of St. Louis College of Pharmacy.