Compounding USP

Compounding

Preparing a drug for an individual patient based on a prescription; NOT FDA-approved.

Commercial Availability Rule

Compounded products must be unique and cannot be commercially available as manufactured products.

Non-Hazardous Compounding Standards

Sterile: USP <797>; Non-Sterile: USP <795>.

Hazardous Compounding Standards

Sterile: USP <797> + <800>; Non-Sterile: USP <795> + <800>.

Aseptic Technique

Procedures to eliminate pathogens and reduce infection risk.

Clean vs. Aseptic vs. Sterile

Clean: free from visible dirt; Aseptic: no disease-causing microbes; Sterile: no microbes at all.

Most Common Contamination Source

People (touching, shedding).

Other Contamination Sources

Supply air, infiltration from adjacent spaces, internal generation from walls/floors/packaging.

Section 503B Outsourcing Facility

Single site compounding sterile drugs; must register with FDA; exempt from FDA approval; must follow CGMP; FDA inspections and adverse event reporting required.

Primary Engineering Controls (PEC)

Where mixing occurs in sterile compounding.

Secondary Engineering Controls (SEC)

The controlled environment or room where compounding occurs.

Horizontal Airflow Hood

Air blows toward worker; for non-chemo preps; HEPA-filtered (99% ≥0.3μm); 90-100 ft/min; sterile, non-hazardous.

Compounding Aseptic Isolator (CAI)

Closed system with glove ports; positive pressure; minimizes contamination; for sterile, non-hazardous.

Vertical Airflow Hood (BSC)

Air flows top-down; protects worker and product; used for hazardous drugs.

Compounding Aseptic Containment Isolator (CACI)

Negative pressure; sealed; for hazardous drugs; vented externally.

ISO Air Quality

PEC = ISO 5; "First air" is cleanest; keep syringe needle and ports in it.

Anteroom (ISO 7)

Positive +0.2 WC to unclassified area; non-hazardous.

Negative Pressure Room (ISO 7)

-0.1 to -0.3 WC relative to ante area; hazardous drugs.

Positive Pressure Room (ISO 7)

+0.2 WC relative to ante area; non-hazardous.

ISO 7 Design Criteria

Temp 68-72°F; humidity 30-60%; ≤30 ACPH; seamless, washable surfaces.

Line of Demarcation

Separates clean and dirty areas.

PEC Cleaning Steps

Use non-shedding wipes → germicidal detergent → sterile IPA; all agents sterile; apply with wipes, not spray.

Cleaning Direction

Clean from buffer to ante area; never reverse.

Daily Cleaning

PEC, equipment, pass-throughs, work surfaces, sinks, floors.

Monthly Cleaning

All surfaces including walls, ceilings, shelves, bins, chairs, PEC interior; includes sporicidal agent.

Designated Person Responsibilities

Train staff, monitor environment, maintain records, certify equipment, assign BUDs, oversee QA/QC.

Donning Sequence

Shoe covers → hair/beard covers → mask → gown → hand wash → sterile gloves disinfected with sterile IPA.

Doffing Sequence

On clean side; remove gloves → hand hygiene → gown → mask → shoe covers → hand hygiene again.

Media Fill Test

Validates aseptic technique (performed once).

Fingertip Test

Validates hand hygiene and garbing (must pass 3 times).

Testing Frequency

Didactic/written annually; semiannual aseptic testing.

ISO 5 Cleanroom Standard

≤3,520 particles ≥0.5μm.

ISO 7 Cleanroom Standard

≤352,000 particles ≥0.5μm.

HVAC Components

Air handling unit, ducts, filters (pre, intermediate, HEPA), dampers, humidifiers.

Environmental Monitoring Parameters

Temp, humidity, pressure, viable/nonviable air, and surface sampling.

ISO 5 Action Levels

Air >1 CFU/m³; Surface >3 CFU/plate.

ISO 7 Action Levels

Air >10 CFU/m³; Surface >5 CFU/plate.

Certification Frequency

Every 6 months by third-party vendor.

Master Formulation Record (MFR)

"How to make it" — includes recipe, container, description, QC tests, and instructions.

Compounding Record (CR)

"What happened" — includes date/time, staff, components, yield, QC results.

Common Record Information

Name, strength, dosage form, BUD/storage.

Category 1 CSP

Unclassified area (SCA).

Category 2 CSP

Full cleanroom.

Category 3 CSP

Cleanroom plus sterility testing.

Immediate Use CSP

≤3 ingredients; administer within 4 hours of preparation.

Category 1 BUD

Room temp ≤12 hr; Fridge ≤24 hr.

Category 2 BUD

Room temp 4 days; Fridge 10 days; Frozen 45 days.

Category 3 BUD (Aseptic)

Room temp 60 d; Fridge 90 d; Frozen 120 d.

Category 3 BUD (Terminally Sterilized)

Room temp 90 d; Fridge 120 d; Frozen 180 d.

Visual Inspection

Check for particles, changes, closures, volume, labeling before dispensing.

USP 795 Scope

Covers non-sterile compounding of oral, rectal, vaginal, topical, nasal, and otic preparations.

USP 795 Exclusions

Immediate use (≤4 hrs), tablet splitting, reconstitution, repackaging.

USP 795 Designated Person

Oversees training, SOPs, storage, monitoring, and component selection.

USP 795 2023 Updates

Report rashes/tattoos; daily temp monitoring; designated area required; CVE certified annually; API must have CoA; visual inspection required.

Non-Sterile Facility Requirements

Separate area from dispensing; ambient air OK; two water types (potable and purified); sink and towels required.

Basic Non-Sterile Equipment

Balance, spatulas, mortar/pestle, beakers, 70% IPA, cleaning agents.

Containment Ventilated Enclosure (CVE)

Lab safety cabinet with HEPA filtration for hazardous or powder materials.

Personal Hygiene (USP 795)

Remove outerwear/jewelry, handwash, wear PPE (gown, gloves, covers, mask).

Non-Sterile Cleaning Frequency

Work surfaces: each shift; Floors: daily; Walls/Shelving: every 3 months; Ceilings: when soiled.

Ingredient Quality Requirements

Use purified water; verify API identity, strength, purity; require CoA and SDS.

USP 795 Master Formulation Record

Describes how to prepare CNSP: container, instructions, final product description, QC.

USP 795 Compounding Record

Documents actual compounding: date/time, personnel, components, yield, QC, linked MFR.

Component Receipt Log

Tracks supplier, lot, quantity, date, exp date, and test results; assign 3-year exp if none provided.

Non-Preserved Aqueous BUD

14 days refrigerated.

Preserved Aqueous BUD

35 days room or fridge.

Nonaqueous BUD

90 days room or fridge.

Solid Dosage Form BUD

180 days room or fridge.

USP 800 Purpose

Reduce exposure to hazardous drugs via specific equipment and procedures.

NIOSH Definition of Hazardous Drug

Carcinogenic, teratogenic, reproductive toxic, organ toxic, or labeled for special handling.

Examples of Hazardous Drugs

Antineoplastics, misoprostol, warfarin, isotretinoin, ribavirin, colchicine, paroxetine.

Safety Data Sheet (SDS)

Content includes PPE, first aid, and spill cleanup procedures; required by OSHA.

Hazard Communication Program

Facility plan for HD safety, SOPs, staff training, HD list review every 12 months.

Medical Surveillance Program

Annual OSHA-required physicals, staff survey, exposure review, lab tests.

Assessment of Risk (AoR)

Evaluates HD type, dosage form, exposure risk, and manipulation.

Low-Risk HD Activities

Counting or packaging using dedicated, decontaminated tray; single chemo glove.

Receiving & Storage Requirements

Unpack in negative pressure (≥12 ACPH); separate, externally vented storage; PPE and spill kits required.

Containment Primary Engineering Controls (C-PEC)

BSC, CVE, or CACI—all negative pressure.

Air Handling for HD Compounding

C-SEC negative pressure; sterile HD = 30 ACPH; non-sterile HD = 12 ACPH.

Biological Safety Cabinet (BSC)

Vertical airflow; protects worker and product; used for chemotherapy prep.

Separation Rules

Sterile and non-sterile compounding ≥1 meter apart; never simultaneous.

Sanitization Steps

1. Deactivate/decontaminate (2% bleach or peroxide) 2. Clean (germicidal detergent) 3. Disinfect (sterile 70% IPA).

USP 800 PPE Requirements

Two chemo-rated gloves, impermeable gown, face mask, head & shoe covers, N95/PAPR if needed.

HD Donning Sequence

Shoe covers (2) → head/facial covers → mask → hand hygiene → gown → inner gloves → enter buffer → chemo gown → outer gloves; change gloves every 30 min.

HD Doffing Procedure

Remove chemo gown, outer gloves, top shoe covers; discard in HD waste bin inside buffer room.

HD Transport Requirements

Label properly; use hard-sided containers for sterile HDs; pneumatic tubes prohibited.

HD Disposal Rules

Yellow bins = trace waste; Black bins = bulk chemo waste (incinerated).

Environmental Monitoring for HDs

Wipe sampling for contamination every 6 months.

Closed System Transfer Devices (CSTD)

Prevent HD vapors from escaping; examples: OnGuard®, Phaseal®, Equashield®, Halo®, Spiros®, ChemoClave®.