USP General Chapter <797>, published by the United States Pharmacopeia (USP), outlines the minimum practices and conditions necessary for the pharmaceutical compounding of sterile preparations (CSPs). The objective of <797> is to prevent patient harm resulting from microbial contamination, excessive bacterial endotoxins, or variability in medication strength. This standard is a legally enforceable set of requirements that applies to compounded medications, such as intravenous (IV) infusions, injections, and ophthalmic solutions. It focuses on controlling the compounding environment, establishing personnel competency, and setting maximum storage times for finished products. The most recent revision became effective in November 2023.
Where the Standard Applies
The requirements of USP <797> apply to all individuals and entities that prepare compounded sterile preparations (CSPs). This includes healthcare settings such as hospital pharmacies, community compounding pharmacies, ambulatory surgery centers, and physician offices. The standard covers a wide variety of sterile products, including injections, inhalations, irrigation solutions for internal body cavities, and eye drops, for both human and animal patients.
Facilities compounding hazardous sterile preparations, such as chemotherapy drugs, must comply with <797> alongside USP Chapter <800>, which focuses on safe handling. Applicability is determined by the preparation process, not the location. Any act involving the combining, diluting, or altering of a drug to create a sterile medication falls under its purview.
Essential Requirements for Sterile Environments
Maintaining a sterile environment relies on engineering controls and rigorous personnel procedures. Compounding must occur within a Primary Engineering Control (PEC), such as a Laminar Airflow Workbench or a Compounding Aseptic Isolator. The PEC must meet International Organization for Standardization (ISO) Class 5 air quality, meaning no more than 3,520 particles of 0.5 micrometers or larger are allowed per cubic meter of air.
The PEC is typically housed within a Secondary Engineering Control (SEC), often called a buffer room, which must maintain at least ISO Class 7 air quality. This buffer room must maintain a positive pressure differential of at least 0.01 inch of water column relative to the adjacent ante-room. This positive pressure ensures that air flows out of the clean area, preventing non-sterile air from entering the compounding space.
Personnel must complete extensive training and qualification. This includes rigorous garbing procedures, involving donning low-lint shoe covers, hair covers, face masks, gowns, and sterile gloves. Competency in hand hygiene and aseptic technique must be demonstrated through initial and annual testing, including media-fill tests that simulate the compounding process to check for microbial growth.
The compounding area requires frequent cleaning and disinfection protocols. Surfaces must be non-porous and resistant to cleaning agents. This regimen mandates the use of both sterile disinfectants and sporicidal agents, with sporicidal agents applied at least monthly to eliminate resistant bacterial spores.
Classifying Sterile Preparations
USP <797> categorizes compounded sterile preparations (CSPs) based on the compounding environment and the resulting Beyond-Use Date (BUD). The BUD is defined as the date and time after which a CSP must not be used, as it is at increased risk for chemical degradation or microbial proliferation. The two main classifications are Category 1 and Category 2 CSPs.
Category 1 CSPs are prepared under the least controlled environmental conditions, specifically in a Primary Engineering Control (PEC) located within a Segregated Compounding Area (SCA). Since this environment has fewer engineering controls than a full cleanroom suite, these preparations are assigned shorter BUDs. Category 1 CSPs may be stored for a maximum of 12 hours at controlled room temperature or 24 hours when refrigerated.
Category 2 CSPs require a full cleanroom suite, which includes an ISO Class 7 buffer room and ante-room. This more controlled environment allows for longer BUDs than Category 1 preparations. The maximum BUD for a Category 2 CSP can be significantly longer, up to 45 days when frozen, depending on the compounding method and whether sterility testing is performed.
There is also a provision for Immediate Use CSPs, which are not subject to the Category 1 or 2 requirements but must be prepared using aseptic technique. This provision is strictly limited to preparations involving not more than three different sterile products. Immediate Use CSPs must be administered within a short timeframe for urgent situations where the full cleanroom process would delay patient care.
Enforcement and Patient Safety
Compliance with USP <797> is generally mandated through state law, as state boards of pharmacy (BOPs) adopt the standards into their regulations. State BOPs are the primary regulatory bodies responsible for inspecting compounding facilities and enforcing environmental and procedural requirements. Accreditation organizations, such as The Joint Commission, also require compliance for certification, which is often tied to government reimbursement programs.
The Food and Drug Administration (FDA) plays a role in oversight, particularly concerning larger “outsourcing facilities” that prepare CSPs for hospitals and clinics. Non-compliance with <797> can result in a compounded drug being considered “adulterated” under federal law, leading to severe regulatory and legal consequences.
Adherence to the standard minimizes the risk of microbial contamination and reduces the presence of pyrogens, which are fever-producing substances. This ensures patients receive medications that are consistently sterile, potent, and safe.