Pharmacy Compounding & Medication Safety: USP, FDA & State Board Compliance Standards

Executive Summary: Compounded medications serve patients who cannot use commercially available products, but compounding errors have caused serious patient harm. This guide covers USP Chapter standards for non-sterile and sterile compounding, FDA oversight framework, state board of pharmacy requirements, and best practices for medication safety in compounding operations.

Regulatory Framework for Pharmacy Compounding

USP Compounding Standards

United States Pharmacopeia (USP) establishes enforceable standards for compounding:

• USP Chapter <795>: Pharmaceutical Compounding—Nonsterile Preparations
• USP Chapter <797>: Pharmaceutical Compounding—Sterile Preparations
• USP Chapter <800>: Hazardous Drugs—Handling in Healthcare Settings
• USP Chapter <825>: Radiopharmaceuticals—Preparation, Compounding, Dispensing, and Repackaging

These standards became legally enforceable when adopted into state pharmacy regulations.

FDA Oversight

The Drug Quality and Security Act (2013) clarified FDA authority over compounding:

• Section 503A: Traditional compounding pharmacies—exempt from certain FDA requirements when compounding patient-specific prescriptions
• Section 503B: Outsourcing facilities—may compound without patient-specific prescriptions but must register with FDA and comply with cGMP
• FDA maintains list of drugs that cannot be compounded
• FDA may inspect compounding facilities and take enforcement action

State Board of Pharmacy Requirements

State boards regulate pharmacy compounding through:

• Licensure requirements for facilities and personnel
• Adoption of USP standards into state regulations
• Inspection and enforcement programs
• Continuing education requirements
• Reporting requirements for adverse events

Non-Sterile Compounding (USP <795>)

Categories of Compounding

USP <795> categorizes non-sterile compounding by complexity:

Category	Description	Examples
Simple	Reconstitution or single modification	Adding vehicle to powder, flavoring
Moderate	More complex calculations or procedures	Ointment/cream compounding, capsule filling
Complex	Requires specialized training or equipment	Modified release preparations, transdermals

Beyond-Use Dating

Non-sterile preparations require appropriate beyond-use dates (BUDs):

• Water-containing oral formulations: 14 days refrigerated (without stability data)
• Water-containing topicals: 30 days (without stability data)
• Non-aqueous formulations: 6 months or 25% of remaining expiration (whichever is shorter)
• Extended dating requires stability studies per USP guidelines

Quality Assurance Elements

• Master formulation records for each preparation
• Compounding records for each batch
• Ingredient verification and documentation
• Calculations verified by second person
• Final product verification (weight, appearance, pH as applicable)
• Proper labeling including BUD

Sterile Compounding (USP <797>)

CSP Categories

Compounded sterile preparations (CSPs) are categorized by risk:

Category	Risk Level	Examples	Maximum BUD (Without Stability Testing)
Category 1	Lower risk	Simple transfers, reconstitutions begun within 12 hours	12 hours at RT; 24 hours refrigerated
Category 2	Higher risk	Complex manipulations, pooling, longer processing	Per USP table based on storage conditions and testing

Facility Requirements

Primary Engineering Controls (PECs):

• Laminar airflow workbenches (LAFWs) providing ISO Class 5 air
• Biological safety cabinets for hazardous drugs
• Compounding aseptic isolators (CAIs) as alternative
• Certification every 6 months and after relocation

Secondary Engineering Controls (SECs):

• Buffer room: ISO Class 7 (or ISO Class 8 with RABS/isolator)
• Ante-room: ISO Class 8 minimum
• Appropriate pressure differentials between areas
• HEPA-filtered air supply
• Temperature and humidity monitoring

Garbing Requirements

Garbing sequence from ante-room to buffer room:

1. Remove outer garments and personal items
2. Don shoe covers (one at a time at demarcation line)
3. Don head cover (all hair contained)
4. Don face mask/beard cover
5. Perform hand hygiene (soap and water; then ABHR)
6. Don non-shedding gown (low-lint)
7. Enter buffer room
8. Apply ABHR
9. Don sterile gloves (apply ABHR to gloves frequently during compounding)

Aseptic Technique

Critical aseptic practices include:

• Maintain first air (uninterrupted HEPA-filtered air to critical sites)
• Work in center of PEC with open vials/needles facing airflow
• Do not obstruct airflow pattern
• Disinfect all surfaces entering PEC with sterile 70% IPA
• Use proper needle/syringe technique to maintain sterility
• Avoid touch contamination of critical sites

Environmental and Personnel Monitoring

Viable Air Sampling:

• ISO Class 5: Monthly minimum
• ISO Class 7/8: Monthly minimum
• Action levels trigger investigation and corrective action

Surface Sampling:

• ISO Class 5: Monthly minimum
• ISO Class 7/8: Monthly minimum
• Include work surfaces, floors, walls, pass-throughs

Gloved Fingertip Testing:

• Initially for all personnel (demonstrate competency)
• At least annually thereafter
• After any suspected contamination event

Media Fill Testing:

• Initial competency demonstration
• At least annually thereafter
• Simulates most complex aseptic manipulations performed
• No growth is passing criterion

Hazardous Drug Handling (USP <800>)

Hazardous Drug Identification

NIOSH maintains list of hazardous drugs. Characteristics include:

• Carcinogenicity
• Teratogenicity or developmental toxicity
• Reproductive toxicity
• Organ toxicity at low doses
• Genotoxicity
• Structure similar to known hazardous drugs

Engineering Controls

• C-PEC (Containment Primary Engineering Control): Biological safety cabinet Class II or CACI
• C-SEC (Containment Secondary Engineering Control): Externally vented, negative pressure room
• Closed-system drug transfer devices (CSTDs) for administration
• Proper ventilation to protect personnel

Personal Protective Equipment

• ASTM-tested chemotherapy gloves (double gloving)
• Disposable gown impervious to hazardous drugs
• Eye/face protection as warranted
• Respiratory protection for spill cleanup or administration concerns

Spill Management

• Spill kits readily available in all HD handling areas
• Personnel trained in spill response
• Contain and clean immediately with appropriate PPE
• Document spill and exposure assessment
• Medical surveillance for exposed personnel

Medication Safety Systems

High-Alert Medications

Institute for Safe Medication Practices (ISMP) identifies high-alert medications requiring additional safeguards:

• Anticoagulants (warfarin, heparin, direct oral anticoagulants)
• Insulin products
• Opioids and concentrated oral solutions
• Neuromuscular blocking agents
• Chemotherapy agents
• Concentrated electrolytes (potassium chloride, sodium chloride >0.9%)

Safety Strategies

• Independent double-checks: Second verification of high-risk calculations and preparations
• Barcode verification: Confirm correct drug and patient
• Standard concentrations: Reduce calculation errors and confusion
• Tall man lettering: Differentiate look-alike drug names
• Limiting access: Remove high-alert medications from floor stock
• Smart pump technology: Drug libraries with dose limits

Look-Alike Sound-Alike Management

• Separate storage of LASA medications
• Use auxiliary labels and alerts
• Tall man lettering on labels and in systems
• Confirm indication when dispensing LASA pairs
• Report near-misses to improve systems

Quality Assurance Program

Required Elements

• Written policies and procedures for all compounding activities
• Master formulation records
• Compounding records with complete documentation
• Personnel training and competency assessment
• Equipment maintenance and calibration
• Environmental monitoring program
• Complaint handling and adverse event reporting
• Self-inspection program

Documentation Requirements

Master Formulation Record:

• Name, strength, dosage form
• Complete ingredient list with quantities
• Equipment required
• Step-by-step compounding instructions
• Quality control tests and specifications
• Beyond-use date assignment rationale
• Storage conditions

Compounding Record:

• Name of preparation and batch number
• Ingredients used (manufacturer, lot, expiration)
• Quantities measured and calculations
• Personnel involved
• Dates and times of compounding steps
• Results of quality testing
• Assigned BUD
• Verification signatures

Conclusion

Pharmacy compounding requires rigorous adherence to USP standards, FDA regulations, and state board requirements to ensure patient safety. Proper facility design, personnel training, aseptic technique, and quality assurance programs minimize contamination and medication errors. Healthcare facilities must invest in appropriate infrastructure, personnel competency, and ongoing monitoring to provide safe compounded medications.

For pharmacy compounding supplies including cleanroom equipment, primary engineering controls, hazardous drug handling supplies, and quality control materials meeting USP standards, explore our pharmacy products catalog.