USP 795/797/800 Compounding Standards

USP 795/797/800 Compounding Standards

Master USP compounding standards with free flashcards and spaced repetition to build lasting knowledge. This lesson covers USP <795> for non-sterile compounding, USP <797> for sterile preparations, and USP <800> for hazardous drug handling—essential standards for NAPLEX success and safe pharmacy practice.

---

Welcome to Compounding Standards Mastery 🧪

The United States Pharmacopeia (USP) establishes critical standards that govern how pharmacies compound medications. These three chapters form the cornerstone of safe compounding practice:

• USP <795>: Non-sterile compounding (creams, capsules, solutions)
• USP <797>: Sterile compounding (IV admixtures, injections, ophthalmics)
• USP <800>: Hazardous drug handling (chemotherapy, hormones)

Understanding these standards isn't just about passing the NAPLEX—it's about protecting patients and staff from contamination, infection, and exposure to dangerous substances. Let's break down each chapter systematically.

---

Core Concept 1: USP <795> – Non-Sterile Compounding 💊

USP <795> governs the preparation of non-sterile compounded preparations (CSPs) that won't be administered via injection or into sterile body cavities.

Key Components of USP <795>

1. Beyond-Use Dating (BUD) ⏰

BUD is the date/time after which a compounded preparation should NOT be used. It's determined by:

💡 Memory Device - "The 14/30/180 Rule":

• 14 days: Water-based oral (you drink it)
• 30 days: Water-based topical (you touch it)
• 180 days: Non-aqueous (no water, longer shelf life)

⚠️ Important: These are MAXIMUM BUDs assuming proper storage and ingredients. Use stability data when available!

2. Facilities and Equipment Requirements

• Designated compounding area: Separate from dispensing, adequate space and lighting
• Calibrated equipment: Balances accurate to ±0.01g for prescription balances
• Master formulation record: Recipe with ingredients, quantities, equipment, BUD calculation
• Compounding record: Batch-specific documentation of who made what, when, and lot numbers

3. Personnel Training and Hygiene 👨‍🔬

• Hand hygiene: Wash hands before and during compounding
• Garbing: Clean lab coat, hair covering when necessary
• Training documentation: Annual competency verification
• Personal protective equipment (PPE): Gloves, masks as appropriate

4. Quality Assurance Activities

• Ingredient verification: Check identity and quality
• Visual inspection: Color, clarity, consistency
• Documentation review: Ensure calculations are correct
• Cleaning logs: Document equipment and area cleaning

---

Core Concept 2: USP <797> – Sterile Compounding 💉

USP <797> governs sterile preparations that will be administered parenterally (IV, IM, SC) or to sterile body sites (eyes, epidural space).

Risk Categories in USP <797>

Sterile preparations are classified by contamination risk:

💡 Memory Device - "1-2-3 Complexity":

• Category 1: Simple (1 = easy, basic IV prep)
• Category 2: Medium (2 = more complex, TPNs)
• Category 3: Challenging (3 = hardest, start non-sterile)

Environmental Controls 🏢

Primary Engineering Control (PEC)

The ISO Class 5 environment where compounding actually occurs:

• Laminar airflow workbench (LAFW): Horizontal or vertical flow
• Biological safety cabinet (BSC): For hazardous drugs
• Compounding aseptic isolator (CAI): Enclosed system
• Compounding aseptic containment isolator (CACI): For hazardous drugs in isolation

Secondary Engineering Control (SEC)

The room containing the PEC:

• Buffer area/room: ISO Class 7 or better, contains the PEC
• Ante-area/room: ISO Class 8 or better, for hand hygiene and garbing

┌─────────────────────────────────────────────────────────┐
│                   ANTE-AREA (ISO 8)                     │
│  🚪 Entry → 🧼 Hand washing → 👔 Garbing                │
│            ↓                                             │
│  ┌─────────────────────────────────────────────────┐   │
│  │        BUFFER ROOM (ISO 7)                      │   │
│  │                                                  │   │
│  │  ┌──────────────────────────────┐              │   │
│  │  │   PEC (ISO 5)                │              │   │
│  │  │   🧪 Actual Compounding      │              │   │
│  │  │   Laminar Flow Hood          │              │   │
│  │  └──────────────────────────────┘              │   │
│  │                                                  │   │
│  └─────────────────────────────────────────────────┘   │
└─────────────────────────────────────────────────────────┘

  Air Quality: ISO 5 (cleanest) < ISO 7 < ISO 8
  Pressure: Positive → Prevents contamination entry

Garbing Requirements for Sterile Compounding 👨‍⚕️

Order matters! Follow this sequence:

1. Remove personal items (jewelry, watches)
2. Don shoe covers
3. Don head/facial hair covers
4. Perform hand hygiene (wash with soap/water)
5. Don gown (non-shedding)
6. Don face mask
7. Enter buffer room
8. Perform antiseptic hand cleansing (alcohol-based sanitizer)
9. Don sterile gloves

💡 Mnemonic - "SHHGG-MHG": Shoes, Head, Hands, Gown, (enter) → Mask (already on), Hands (antiseptic), Gloves

Personnel Competency Assessment 📋

Initial training must include:

• Written test: Understanding of principles
• Media fill test (process simulation): Compound with tryptic soy broth (TSB) instead of drug, incubate 14 days
  • Must pass 3 consecutive media fills
  • Zero growth = Pass

Ongoing competency:

• Annual media fill for low/medium risk
• Semi-annual media fill for high risk
• Annual written assessment

---

Core Concept 3: USP <800> – Hazardous Drug Handling ☢️

USP <800> protects healthcare personnel from exposure to hazardous drugs (HDs) that pose risks including carcinogenicity, teratogenicity, reproductive toxicity, organ toxicity, and genotoxicity.

What Are Hazardous Drugs?

HDs are classified into three groups:

NIOSH (National Institute for Occupational Safety and Health) maintains the definitive list of hazardous drugs, updated regularly.

Engineering Controls for Hazardous Drugs 🛡️

Containment Primary Engineering Controls (C-PEC)

HDs must be compounded in:

• Class II or III Biological Safety Cabinet (BSC)
• Compounding Aseptic Containment Isolator (CACI)

These provide:

• Product protection (sterility)
• Personnel protection (containment)
• Environmental protection (filtered exhaust)

Key Features:

• Negative pressure relative to surrounding area
• Externally vented (exhausted outside building, not recirculated)
• HEPA filtration on exhaust

┌─────────────────────────────────────────────────────────┐
│     HAZARDOUS DRUG COMPOUNDING SUITE                    │
│                                                          │
│  ┌────────────────────────┐    ┌──────────────────┐   │
│  │  ANTE-ROOM (ISO 7-8)   │    │  BUFFER ROOM     │   │
│  │  • Unpacking           │◄───│  (Negative       │   │
│  │  • Deactivation        │    │   Pressure)      │   │
│  │  • Decontamination     │    │  ┌─────────────┐ │   │
│  └────────────────────────┘    │  │   C-PEC     │ │   │
│           ↕                     │  │   (BSC/     │ │   │
│      Normal pressure            │  │    CACI)    │ │   │
│                                 │  └─────────────┘ │   │
│                                 │       ↓          │   │
│                                 │   HEPA filter    │   │
│                                 │       ↓          │   │
│                                 │  🌬️ Vented out   │   │
│                                 └──────────────────┘   │
└─────────────────────────────────────────────────────────┘

Personal Protective Equipment (PPE) for HDs 🧤

Receiving/Unpacking/Transporting:

• Chemotherapy gloves (ASTM D6978-05 tested)
• Gown

Compounding:

• Double chemotherapy gloves (change outer every 30 minutes)
• Non-shedding gown with closed front, tight cuffs
• Hair/beard covers
• Shoe covers
• Respiratory protection if risk of airborne exposure
• Face shield if splash risk

Administering:

• Single chemo gloves
• Gown
• Face/eye protection if splash risk

💡 Critical Detail: Standard latex/nitrile exam gloves are NOT sufficient—must be chemotherapy-tested gloves!

Spill Management 🚨

Small spill (<5 mL or 5 g):

1. Restrict access
2. Don full PPE
3. Use spill kit:
   • Absorbent pads
   • HD disposal bags
   • Deactivating/cleaning agents
4. Clean from outside toward center
5. Dispose in HD waste

Large spill (>5 mL or 5 g):

• Evacuate area
• Call trained spill team
• May require environmental services

Decontamination and Cleaning 🧹

• Daily cleaning of C-PEC surfaces
• Weekly cleaning of floors, walls, ceilings in HD areas
• Use deactivating agents (sodium hypochlorite, peroxide) when appropriate
• Use disposable cleaning materials
• Document all cleaning activities

---

Example 1: Calculating BUD for Non-Sterile Compounding

Scenario: You're compounding a hydrocortisone 2% cream using:

• Hydrocortisone powder (expires in 2 years)
• Hydrophilic ointment base (expires in 1 year)

Question: What is the maximum BUD for this preparation stored at room temperature?

Solution:

Answer: The maximum BUD is 180 days from the date of compounding.

💡 Key Takeaway: Non-aqueous formulations get the longest BUD (180 days), but this can be limited by ingredient expiration dates or stability data.

---

Example 2: Classifying Sterile Preparation Risk

Scenario A: Pharmacist adds 1 g cefazolin from a vial into a 50 mL minibag of NS for a single patient. Prepared in ISO 5 hood inside ISO 7 buffer room.

Analysis:

• ≤3 sterile products? ✅ (2 products: vial + bag)
• ≤2 entries per container? ✅ (1 entry into bag)
• Single patient? ✅

Classification: Category 1 (simple, low risk)

BUD at room temperature: 12 hours

---

Scenario B: Pharmacist prepares a total parenteral nutrition (TPN) bag combining:

• Amino acids 10%
• Dextrose 70%
• Lipid emulsion 20%
• Multiple electrolyte vials (sodium, potassium, calcium, etc.)
• Multivitamins
• Trace elements

Prepared in ISO 5 hood with proper environmental monitoring.

Analysis:

• ≤3 sterile products? ❌ (>10 ingredients)
• Multiple entries? ✅
• Complex mixing? ✅

Classification: Category 2 (medium risk, multiple ingredients)

BUD at room temperature (with ISO 5 documentation): 24 hours

💡 Important: TPNs are classic Category 2 CSPs because they require combining many ingredients with extended manipulation time.

---

Example 3: Proper Garbing Sequence

Scenario: A pharmacy technician is about to compound sterile IV admixtures. What is the correct garbing sequence?

Correct Sequence:

⚠️ Common Error: Putting on gloves before entering the buffer room. Sterile gloves should be the LAST item donned, after antiseptic hand cleansing in the buffer room.

---

Example 4: Hazardous Drug Handling Decision

Scenario: A pharmacy receives prescriptions for:

1. Cyclophosphamide 50 mg tablets (dispense 28 tablets)
2. Finasteride 5 mg tablets (dispense 30 tablets)
3. Doxorubicin 50 mg injection for compounding

Question: Which require hazardous drug precautions per USP <800>?

Analysis:

Answer: ALL three require precautions, but the level varies:

• Intact tablets: Minimal precautions (gloves)
• Compounding: Full engineering controls (C-PEC) and extensive PPE

💡 Key Point: Even dispensing intact HD tablets requires basic precautions because tablets can chip or break, creating dust exposure.

---

⚠️ Common Mistakes to Avoid

Mistake #1: Confusing BUD with Expiration Date

ERROR: "This bottle expires in 2025, so my compounded preparation is good until then."

CORRECTION: BUD is based on USP standards (14/30/180 day rules for non-sterile, risk categories for sterile) AND ingredient expiration dates. Use the more conservative (shorter) date.

---

Mistake #2: Wrong Environmental Controls for Hazardous Drugs

ERROR: Compounding chemotherapy in a standard horizontal laminar flow hood.

CORRECTION: Hazardous drugs MUST be compounded in a containment device (BSC or CACI) with negative pressure and external venting. Regular hoods blow air at the operator—dangerous with HDs!

❌ WRONG: Horizontal LAFW for HDs
     Air ─────────→ 👨 (operator exposed!)
     HD particles blown at you

✅ CORRECT: BSC for HDs
     Air ↓ (captured by HEPA)
     👨 ← Barrier protects operator
     Exhaust filtered and vented outside

---

Mistake #3: Incorrect Garbing Order

ERROR: Putting on sterile gloves in the ante-room, then touching the door to enter the buffer room.

CORRECTION: Sterile gloves are the LAST item donned, AFTER entering the buffer room and performing antiseptic hand cleansing. This prevents contamination from touching non-sterile surfaces.

---

Mistake #4: Inadequate HD PPE

ERROR: Using regular nitrile exam gloves when handling chemotherapy.

CORRECTION: Must use chemotherapy-tested gloves that meet ASTM D6978-05 standards. Regular gloves provide inadequate protection against cytotoxic drug permeation.

---

Mistake #5: Misclassifying Sterile Preparation Risk

ERROR: Calling a TPN "Category 1" because it's for one patient.

CORRECTION: Category depends on complexity, not just patient number. TPNs are Category 2 due to multiple ingredients (>3 products) and extended compounding time, even for a single patient.

---

Mistake #6: Forgetting Media Fill Testing

ERROR: Training staff on aseptic technique through demonstration only, without competency testing.

CORRECTION: USP <797> REQUIRES initial and ongoing media fill testing (process simulation with growth medium). Must pass 3 consecutive media fills initially, then annually (or semi-annually for high risk).

---

🧠 Memory Aids and Mnemonics

The "3 USP C-Standards"

• USP <7-9-5>: Non-Sterile (7+9+5 = 21 = age you can drink = oral meds)
• USP <7-9-7>: Sterile (797 = "seven-ninety-SEVEN" = needles look like 7)
• USP <8-0-0>: Hazardous (800 = big number = big danger)

BUD Quick Reference: "14-30-180"

• 14: Water-based oral ("14 days to drink it")
• 30: Water-based topical ("30 days to rub it")
• 180: No water ("180 = half of 360 degrees = half a year")

Garbing Order: "Shoes Head Hands Gown → Go → Mask Hands Gloves"

S-H-H-G (ante-room) → Go (enter buffer) → M-H-G (buffer room)

ISO Classes: "5-7-8" = Cleaner → Dirtier

• ISO 5: Inside the hood (5 fingers on one hand = primary)
• ISO 7: Buffer room (7 days in a week = secondary)
• ISO 8: Ante-room (8 legs on spider = outer area)

---

🔑 Key Takeaways

---

📚 Further Study

1. USP Official Standards: www.usp.org/compounding - Access official USP chapter texts and updates

2. NIOSH List of Hazardous Drugs: www.cdc.gov/niosh/topics/antineoplastic/ - Current list of hazardous drugs in healthcare settings

3. FDA Compounding Guidance: www.fda.gov/drugs/human-drug-compounding - Regulatory perspective on compounding pharmacy practice

---

🎯 You now have the foundation to tackle NAPLEX questions on compounding standards! Remember: These aren't just test topics—they're the practices that keep patients and healthcare workers safe every single day.