The United States Pharmacopeia (USP) General Chapter outlines standards for Pharmaceutical Compounding – Sterile Preparations (CSPs) to ensure patient safety by minimizing risks of contamination, errors, and variability. The revised version, effective November 1, 2023, represents a major update from the 2008 edition, shifting from risk-level classifications (e.g., low-, medium-, high-risk) to a category-based system focused on compounding environment, controls, and validation. This guide provides accurate, detailed information on Beyond-Use Dates (BUDs), categories, storage, extensions, testing, environmental controls, personnel requirements, facility design, and compliance. It is based on the official USP chapter and supporting resources from USP, ASHP, and other authoritative sources.
Key changes in the 2023 revision include:
Elimination of risk levels in for of Categories 1, 2, and 3.
Emphasis on facility design, garbing, monitoring, and testing for longer BUDs.
Updated BUD limits, with options for extensions via validation.
Stricter requirements for nonsterile starting components, terminal sterilization, and multiple-dose preparations.
Removal of references to hazardous drugs (now in ) and radiopharmaceuticals (in ).
Allowance for validated alternative technologies if noninferior to standards.
This content prioritizes patient safety, regulatory compliance, and practical implementation.
Definitions and General PrinciplesA Beyond-Use Date (BUD) is the date or time after which a CSP must not be used, stored, transported, or administered, and must be discarded. It is determined from the date and time compounding is completed and must be shorter than or equal to the earliest expiration date of any ingredient or the chemical stability of the CSP. BUDs account for risks of microbial contamination, chemical degradation, and physical changes, ensuring the preparation remains safe and effective.
Key principles for assigning BUDs:
Stability and Sterility: BUDs must be supported by stability-indicating data (e.g., from literature, studies, or monographs) and consider sterility risks. Use methods like high-performance liquid chromatography (HPLC) to confirm active ingredients remain within limits (e.g., 90–110% potency).
Compounding Environment and Controls: Categories determine baseline BUDs, with extensions requiring enhanced monitoring, testing, and validation.
Storage Conditions: Controlled room temperature (CRT: 20–25°C), refrigerated (2–8°C), or frozen (–25°C to –10°C). Colder storage generally extends BUDs but must not compromise stability.
Starting Components: Sterile vs. nonsterile ingredients affect BUDs; nonsterile require sterilization (aseptic processing or terminal sterilization).
Processing Method: Terminal sterilization (e.g., autocling, achieving