1.2 USP Standards & Applicability (<795>, <800>, <1163>)

1.2 USP Standards & Applicability (<795>, <800>, <1163>)

The United States Pharmacopeia (USP) is an independent, non-governmental, non-profit standards-setting organization. Under the federal FD&C Act and state pharmacy practice acts, USP standards establish the enforceable benchmarks for medicine strength, quality, purity, packaging, and compounding practice. Understanding how USP chapters are structured, interpreted, and applied is a core domain for the PTCB Nonsterile Compounding Certificate.

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Structure and Legal Authority of USP Chapters

USP standards are published in the United States Pharmacopeia–National Formulary (USP–NF). Chapter numbering is a useful navigation signal, but it is not a stand-alone test of legal enforceability:

• General Chapters below <1000>: These may contain compendial requirements when they are made applicable by a monograph, General Notices, federal law, or an adopting regulator. The number alone does not make every sentence enforceable in every setting.
• General Chapters <1000> through <1999>: These generally provide information, recommendations, and supporting science unless another applicable standard or regulator expressly makes a provision controlling.
• Applicable jurisdiction controls enforcement: USP establishes standards but does not inspect or enforce them. Candidates must consult USP General Notices—especially compounding applicability—and the laws and rules adopted by the relevant regulator.

Three key chapters form the cornerstone of nonsterile compounding governance:

1. USP Chapter <795> – Pharmaceutical Compounding – Nonsterile Preparations
2. USP Chapter <800> – Hazardous Drugs – Handling in Healthcare Settings
3. USP Chapter <1163> – Quality Assurance in Pharmaceutical Compounding

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USP Chapter <795>: Nonsterile Compounding Standards

USP Chapter <795> sets mandatory requirements for compounding nonsterile drug preparations for human and animal patients. The revised USP <795>, published November 1, 2022 and official November 1, 2023, replaced the former simple/moderate/complex categories. Current study should focus on whether an activity is within <795> scope and on the controls required for the actual process.

Scope and Process Evaluation

• Reconstituting a conventionally manufactured product exactly according to its FDA-approved labeling is outside <795>; deviating from those directions is compounding.
• Cutting a tablet or repackaging a conventionally manufactured product is outside the chapter’s compounding scope.
• The facility must evaluate particle-generating steps such as weighing or manipulating powders to decide whether a closed-system processing device is needed.
• Nonsterile hazardous-drug compounding must also comply with USP <800> and applicable jurisdictional requirements.

Beyond-Use Date (BUD) Rules under USP <795> (2023 Revision)

A Beyond-Use Date (BUD) is the date or time after which a compounded preparation must not be used, stored, or transported. It is calculated from the date and time the preparation is compounded. Unlike commercial expiration dates (which are determined through extensive manufacturer stability testing), BUDs for compounded nonsterile preparations (CNSPs) are assigned conservatively based on chemical stability, physical integrity, and microbial contamination risk.

Under the revised USP <795> framework, default BUD limits for CNSPs packaged in tight, light-resistant containers (in the absence of stability-indicating analytical studies) are determined by water content/activity and storage temperature:

CRITICAL RULE FOR BUD ASSIGNMENT: The assigned BUD can NEVER exceed the shortest expiration date of any individual active pharmaceutical ingredient (API) or excipient used in the compound! If an API expires in 45 days, a nonaqueous capsule BUD must be capped at 45 days, even though the USP default limit is 180 days.

Extending BUDs Beyond Default Limits

To assign a BUD longer than the USP <795> default limits, the pharmacy must obtain documented stability data derived from a stability-indicating analytical method performed on the specific formulation in its specific container-closure system, alongside meeting antimicrobial effectiveness testing requirements (USP <51>).

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USP Chapter <800>: Hazardous Drugs in Nonsterile Compounding

USP Chapter <800> applies to all healthcare personnel who handle Hazardous Drugs (HDs), including receipt, storage, compounding, dispensing, and disposal. The primary goal of USP <800> is worker protection and environmental containment.

Identifying Hazardous Drugs: The NIOSH List

The current NIOSH List of Hazardous Drugs in Healthcare Settings, 2024 supersedes the 2016 list and uses two tables, not the former three-group structure. Table 1 contains drugs with manufacturer’s special handling information; Table 2 contains drugs that meet the NIOSH hazardous-drug definition without that labeling. Developmental and reproductive hazards are identified within those tables rather than placed in a separate Table 3. Always use the current list plus later NIOSH notices and the entity-specific hazardous-drug list.

Engineering Controls for Nonsterile Hazardous Compounding

Nonsterile hazardous compounding requires strict physical containment to prevent airborne dust, aerosols, or cross-contamination:

1. Containment Primary Engineering Control (C-PEC): The ventilated cabinet where HD compounding occurs. Acceptable C-PECs for nonsterile HD compounding include:
   • Class I or Class II Biological Safety Cabinet (BSC); or
   • Containment Ventilated Enclosure (CVE) (commonly known as a powder hood).
2. Containment Secondary Engineering Control (C-SEC): The room housing the C-PEC. For nonsterile HD compounding, the C-SEC must:
   • Maintain negative pressure between -0.010 and -0.030 inches of water column relative to adjacent areas;
   • Be externally vented to the outdoors; USP <800> does not require the room exhaust itself to pass through HEPA filtration; and
   • Achieve at least 12 Air Changes Per Hour (ACPH).

[ C-SEC: Negative Pressure Room (-0.01 to -0.03" w.c., 12 ACPH) ]
       │
       ├──> Contains C-PEC (Class I/II BSC or CVE)
       └──> Externally Vented Exhaust Air to Environment

1. Deactivation, Decontamination, and Cleaning: All areas where HDs are handled and reusable equipment must be deactivated, decontaminated, and cleaned using agents appropriate for the drug and surface. Disinfection is an additional required step for sterile compounding areas, not a universal fourth step for every nonsterile HD surface. Product labels and entity SOPs determine the agents and contact times.

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USP Chapter <1163>: Quality Assurance in Pharmaceutical Compounding

USP Chapter <1163> outlines the structural elements necessary to build an effective Quality Assurance (QA) and Quality Control (QC) program for compounding facilities.

Distinction Between Quality Assurance and Quality Control

• Quality Assurance (QA): The set of planned, systemic administrative and operational procedures designed to ensure that compounding processes consistently produce high-quality preparations meeting predefined standards. QA is process-oriented and proactive (e.g., writing SOPs, training staff, calibrating equipment).
• Quality Control (QC): The system of physical checks, sampling, and analytical testing used to measure and verify the quality of specific raw materials, components, and finished compounded preparations. QC is product-oriented and corrective (e.g., verifying weights, testing pH, visual inspection, assay testing).

Core Elements of USP <1163>

1. Standard Operating Procedures (SOPs): Detailed, step-by-step written instructions covering every aspect of facility operation, garbing, cleaning, compounding, calibration, documentation, and waste handling.
2. Ingredient Verification: Verification that ingredients possess an authentic Certificate of Analysis (CoA) and meet USP/NF specifications.
3. Equipment Calibration and Maintenance: Regular calibration schedules for digital analytical balances, pH meters, magnetic stirrers, and temperature-monitoring sensors.
4. Out-of-Specification (OOS) Investigations: A formal, documented procedure for investigating any batch or compound that fails to meet physical, chemical, or microbial parameters, establishing root cause and corrective actions (CAPA).