Designing Pharmacy Cleanrooms to Comply with USP 797 & 800 Guidelines

March 11, 2025 // Insights; Healthcare

Why This Topic?

Designing high performing pharmacy cleanrooms are critical to preventing patient harm from contaminated pharmaceuticals and limiting healthcare workers exposure to hazardous drugs that have a serious risk of adverse health effects.  The strict operational standards and best practices pose several implications for the space planning and design of these spaces. Pharmacy clean compounding rooms are complex spaces to construct, operate, and maintain in a healthcare facility due to the density of building systems and the stringent operating procedures required to keep the environment clean and safe.

In 2014 and 2016, The United States Pharmacopeia (USP) released USP General Chapters 797 and 800, respectively, with an initial planned effective date in December 2019. To achieve USP compliance, a design team lead by Perspectus and consisting of, Hasenstab, IMEG, and Smith Seckman Reid (SSR) designed renovations for twenty-eight pharmacies throughout the University Hospitals of Cleveland system, with projects to be completed by the end of 2019.

The official enforcement of United States Pharmacopeia (USP) guidelines for clean compounding rooms went into effect in November 2023, and several common areas of scrutiny have emerged.  In this overview, we will discuss the design of pharmacy cleanrooms for safety, operational efficiency, and compliance with USP 797 and 800, while providing insights into potential solutions for common challenges.

This material was presented at the 2024 PDC Summit as an educational session titled “Designing Spaces to Comply with USP 797 & 800”. The presenters included Bradley Fink, AIA, Principal at Perspectus; Bridget Gegorski, PharmD, MS, BCSCP, Medication Safety Officer at University Hospitals; Ray Minotas, AIA, ACHA, Principal at Perspectus; and Brian Widowski, PE, MBA, Senior Project Manager at Smith Seckman Reid (SSR).

United States Pharmacopeia (USP)

Established in 1820, USP aims to ensure the quality of drug products. It is a non-profit standards-setting organization, not a government entity, and has no role in enforcement. However, USP General Chapters are recognized under the Federal Food, Drug, and Cosmetic (FD&C) Act, with specific chapters referenced in the Code of Federal Regulations. State boards of pharmacy determine which parts to implement, resulting in varying degrees of stringency across states. With the implementation of these guidelines, several common areas of scrutiny have emerged.  In the following sections, we will explore key considerations in designing pharmacy cleanrooms for safety, operational efficiency, and compliance, while addressing potential challenges and solutions.

Why All This Attention?

Historical Context

With the implementation of these guidelines, several common areas of scrutiny have emerged.  In the following sections, we will explore key considerations in designing pharmacy cleanrooms for safety, operational efficiency, and compliance, while addressing potential challenges and solutions. USP 797 was first published in 2000 and has undergone several updates, the most recent in November 2023. Regulatory enforcement increased significantly after the 2012 NECC tragedy, where poor compounding conditions led to a fungal meningitis outbreak, resulting in numerous patient deaths and illnesses. This tragedy prompted stricter regulatory oversight and the establishment of the Drug Quality and Security Act (DQSA) in 2013, which includes direct FDA oversight of certain types of compounding pharmacies.

Sterile Compounding and HD Handling Enforcement

As a result of these developments, regulatory agencies have taken on a more active role in ensuring compliance with sterile compounding and hazardous drug handling. The FDA regulates 503b pharmacies directly but also reserves the right to inspect hospital 503a pharmacy cleanrooms. State Boards of Pharmacy primarily oversee hospital pharmacies and enforce compliance with state-specific USP rules. Additionally, the Centers for Medicare and Medicaid Services (CMS) include these regulations as part of the Conditions of Participation (CoP), which affect accreditation status and the ability to serve CMS patients. OSHA may also investigate USP 800 violations due to its focus on employee safety. This multifaceted regulatory environment adds significant pressure on pharmacy design teams to create spaces that meet both state and federal regulations.

USP 797 Pharmaceutical Compounding – Sterile Preparations

With the goal of preventing patient harm, USP 797 focuses on eliminating contamination risks in sterile compounding environments, particularly from microbial contamination and excessive bacterial endotoxins. Key changes in the November 2023 update include new training, garbing requirements, updated sampling protocols, and revised facility standards. The most significant change is the new Beyond-Use Date (BUD) determination, now based on the environment in which a compound is prepared.

• Category 1 compounds: Prepared in a Primary Engineering Control (PEC) not located within a Secondary Engineering Control (SEC), with specific placement and cleaning requirements. These compounds have a BUD of 12 hours at room temperature and 24 hours under refrigeration. 

• Category 2 compounds: Prepared in PECs located within the SEC buffer room, with a BUD of 4 days at room temperature and 10 days under refrigeration. Compounds prepared in a hood within a compliant clean room are classified as Category 2 compounds.

Other notable changes include HEPA filters located in ceilings, hands-free door access, and stricter temperature and humidity recommendations to improve the comfort of compounding staff and reduce contamination risks. To ensure compliance, cleanroom designs must integrate specific engineering solutions to accommodate the updated BUD requirements and facility standards.

USP 800 Hazardous Drugs – Handling in Health Care Settings

USP 800 outlines requirements for handling hazardous drugs to prevent unnecessary employee exposure. It most commonly applies to facilities treating oncology patients and mandates appropriate facilities to handle drugs classified as hazardous on the NIOSH list. This chapter became enforceable with the recent updates to USP 797 and 795 in November 2023. This shift has major implications for pharmacy design, especially in how hazardous drugs are received, stored, and compounded.  A closer look at how these requirements impact different room types provides valuable insight into the design considerations necessary to ensure compliance.

Room Types

Workroom

While the focus of USP 797 and 800 is on the cleanroom suite, the design of the pharmacy workroom must be carefully considered to accommodate the workflow and safety measures of the cleanrooms. The workroom is the primary space for non-sterile activities, including zones for dispensing medications, storage, packaging, and staff offices. Compounding of non-sterile medications may occur in the workroom and must adhere to USP 795 standards for non-sterile pharmaceutical compounding. The unpacking and storage of hazardous drugs present unique challenges.  A dedicated hazardous drug unpacking room is required to prevent contamination in the event of spills or punctures.

Hazardous Storage / Receiving

One of the key spaces identified in USP 800 is a physically separate room for unpacking hazardous drugs to contain potential punctures or spills. Ideally, this room adjoins the Hazardous Drug Buffer Room to allow for the direct transfer of hazardous drugs into the compounding area. If located remotely, additional procedures such as double-bagging hazardous drugs and extra cleaning are required. This room must be easily cleanable, externally vented, and maintain negative pressure.

Ante Room

The Ante Room serves as a transition zone for staff cleaning, donning and doffing, and helps limit contamination transmission between the workroom and the cleanroom. If space allows and contamination is a concern, a series of ante rooms may be considered, providing a dry transition area between the scrub sink and the clean rooms.

Non-Hazardous Buffer Room

Designed for sterile, non-hazardous drug compounding, such as intravenous medication preparation, the Non-Hazardous Buffer Room is intended to create a clean working environment that eliminates the risk of patient infection from contaminated drugs.

Hazardous Buffer Room

This room is used for handling and compounding sterile hazardous drugs, with operational and facility requirements outlined in USP 800. It is designed to create a clean working environment that eliminates the risk of patient infection from contaminated drugs while also protecting staff from exposure to hazardous drugs.

Planning Considerations

Adjacencies

The orientation and location of the cleanroom suite are vital to mitigating common issues. Pay close attention to the spaces above, below, and beside the cleanrooms. Avoid placing drains and other building infrastructure that do not serve the suite above the ceiling. Similarly, toilet rooms, kitchens, or other potential sources of contamination should not be located adjacent to the cleanrooms.

Entry

Personnel enter cleanrooms through the Ante Room and interlocking doors, while hazardous drugs are delivered through the Hazardous Drug Storage & Receiving Room.

Pass-Thru

To minimize the need for garbing, supplies are passed into the Clean Room through pass-thru cabinets, and compounded drugs are transferred back to the workroom for administration or dispensing.

Visibility

Visual and audio connectivity between the cleanrooms and the workroom is required for communication, coordination, and safety procedures. This can be facilitated through windows, intercoms, and cameras.

Engineering Criteria

Designing compounding pharmacies presents significant challenges, with mechanical systems playing a critical role in their success or failure. The American Society for Healthcare Engineering (ASHE) has provided comprehensive guidance on this topic, particularly in a monograph authored by Benjamin Leutze.

Proximity and Cleanliness Requirements

The design complexity of compounding areas increases as the proximity to the compounding activity increases. This relationship is crucial because higher cleanliness standards are required closer to the compounding process.

Direct Compounding Area (DCA)

• ISO Class 5 Requirement: The DCA must be located within an ISO Class 5 space, with lower ISO numbers indicating cleaner spaces.

• Cleanliness Gradient: As you move outward from the DCA, spaces progressively become less clean, culminating in areas such as the stockroom or general pharmacy area, which have less stringent cleanliness requirements.

Room Definitions and Specifications

Non-Hazardous Buffer Room (Positive Pressure Room)

• Usage: Typically a busy space that contains room-side controls for the ISO Class 5 DCA.

• Pressure Requirements: Must maintain positive pressure relative to all adjacent spaces.

• Features: Equipped with hoods that recirculate air within the room to maintain cleanliness.

Hazardous Buffer Room (Negative Pressure Room)

• Usage: Commonly used in facilities with cancer treatment activities that require handling hazardous drugs.

• ISO Class: Must meet ISO Class 7 standards with ISO Class 5 hoods.

• Pressure Requirements: All air must be exhausted to the outdoors with no recirculation. Although a negative pressure room, it must maintain positive pressure relative to the work room to ensure filtered air flow.

• Air Supply: The adjacent ante room serves as the make-up air source for the hazardous room and must match its cleanliness level.

• Hazardous Storage: Typically ISO Class 9 (general room) but must be negative pressure and exhaust air due to the hazardous nature of the materials stored.

Personnel and Environmental Considerations

Personnel working in these environments must adhere to strict protocols to ensure safety and maintain cleanliness standards:

• Personal Protective Equipment (PPE): Staff are not permitted to enter these rooms in street clothes. Instead, they wear scrubs and PPE, often in multiple layers, especially in hazardous rooms.

• Environmental Conditions: These spaces are small and contain various heat-generating equipment such as computers, hoods, and refrigerators. Combined with staff wearing multiple layers of PPE, this creates a significant internal heat load. It is essential to keep these spaces cool to maintain both comfort and cleanliness.

Challenges and Opportunities

Renovating existing pharmacies to meet USP 797 and 800 standards often requires careful planning and execution to ensure that operations can continue uninterrupted.  Important considerations include thoughtful construction phasing, optimizing the allocation of space, selecting the right products, and servicing the completed spaces.

Phasing

Phasing is a significant challenge in healthcare renovation projects, including pharmacy redesigns. Temporary outdoor trailers or compounding rooms may be practical solutions at some sites but must remain in close proximity to the clinical care areas and may require new operating procedures. For a campus or health system with multiple pharmacies, there is an opportunity to consolidate services into a single pharmacy for a limited duration. This approach optimizes space while ensuring continuity of essential services without compromising patient care.

Space

Efficient space utilization is critical in pharmacy design, especially in optimizing cleanroom areas where sterile drug compounding occurs. Consideration should be given to smaller cleanrooms, where feasible, to limit the area subject to special cleaning and maintenance, while maximizing storage and working space in the non-sterile work room. Additional barriers or ante rooms are essential for enhancing infection control and safety measures, particularly when pharmacies have direct access to outdoor environments.

Products

The selection of pharmacy equipment and materials presents specific challenges. For instance, pass-throughs must meet both functional and durability standards, while the design and operation of sinks, including eye-wash capabilities, require careful consideration for hands-free operation and ease of use. The choice of wall paint sheen and ceiling types (lay-in versus hard) can affect cleanliness and maintenance requirements. Additionally, lighting and diffusers must be suitable for use in a cleanroom environment, with details such as gasketing, fasteners, and joints requiring thorough evaluation.

Operation

Operational considerations include serviceability, balancing during startup, and commissioning processes. Designing for room comfort may exceed performance requirements for room temperature and humidity, requiring careful analysis to balance staff comfort with the capabilities of the building systems. Additionally, designing spaces that facilitate efficient workflow and maintenance operations enhances overall operational efficiency and staff satisfaction.

Interpretation of Codes/Guidelines

Interpreting and adhering to regulatory codes and guidelines are fundamental in pharmacy design. This includes understanding requirements for alarm systems, ante room door swings, and cleanliness standards. Establishing processes for recertification ensures ongoing compliance and operational readiness, emphasizing the need for robust quality assurance protocols throughout the design and construction phases.

Conclusion

Designing and operating pharmacy cleanrooms requires meticulous planning and adherence to stringent guidelines to ensure safety and efficiency. With recent updates to USP 797 and 800, staying informed and compliant with these standards is crucial to protect patients and staff, as well as to maintain accreditation. Understanding the objectives of the standards, engaging the clinical team in their workflow, and collaborating with facility staff on operations will result in solutions that are both compliant and functional.

Contact us to further explore how Perspectus can assist in achieving compliance and the design of Pharmacy cleanrooms; bfink@perspectus.com | rminotas@perspectus.com.