Section 13.1: USP <795>, <797>, and <800> Standards Overview

13.1.1 The “Why”: Moving Beyond Memorization to Mastery

As a practicing pharmacist, you have undoubtedly encountered the United States Pharmacopeia (USP) chapters on compounding. Perhaps it was during a pharmacy school lab, a continuing education module, or a frantic search to determine a beyond-use date (BUD) for a pediatric suspension. For many, these chapters—<795>, <797>, and <800>—exist as a dense, intimidating, and often fragmented set of rules to be memorized or referenced as needed. The transition from pharmacist to operations manager demands a fundamental shift in this perspective. These chapters are no longer just rules to be followed; they are the architectural blueprints for your entire compounding operation.

Your role is to move beyond mere compliance with individual clauses and to develop a holistic, operational mastery of the principles that underpin them. You are no longer just answering “What is the rule for this?”; you are now responsible for answering “How do I design a system, train a team, and manage a facility that makes compliance with this rule an ingrained, default behavior?” This requires a deep understanding of the “why” behind each standard. Why is negative pressure required for hazardous drugs? Why is garbing performed in a specific sequence? Why are BUDs for water-containing formulations so much shorter than for non-aqueous ones?

The answer to every one of these questions boils down to one of three fundamental pillars of safety:

1. Patient Safety from Inaccurate Dosing & Contamination (<795>): Ensuring the non-sterile product is chemically stable, potent, and free from gross contamination for its intended duration of use.
2. Patient Safety from Microbial Invasion (<797>): Protecting the most vulnerable patients from catastrophic harm by ensuring sterile products are free from microorganisms and their byproducts. This is an absolute, life-or-death standard.
3. Personnel Safety from Hazardous Exposure (<800>): Protecting your team—your most valuable asset—from the insidious, long-term health risks associated with handling hazardous drugs.

This section will deconstruct these three foundational chapters from a manager’s perspective. We will translate the regulatory language into operational checklists, facility design considerations, and staff training requirements. Your goal is not to become a walking encyclopedia of USP standards, but to become an operational architect who can build a robust, safe, and efficient compounding service line from the ground up, with these standards as your unshakeable foundation.

13.1.2 Deep Dive: USP General Chapter <795> – Pharmaceutical Compounding – Nonsterile Preparations

USP <795> provides the minimum standards for the compounding of nonsterile preparations for human and animal patients. While often associated with simple compounds like “Magic Mouthwash” or dermatological creams, its scope and importance are far broader. It governs any manipulation of commercial products (e.g., crushing tablets to make a suspension) and the creation of formulations from bulk chemical ingredients. As a manager, you must view <795> as the foundational layer of patient safety for customized medications. Its primary goal is to prevent harm that could result from microbial contamination, excessive microbial growth, variability from the intended strength, poor-quality ingredients, or physical and chemical incompatibilities.

Pillar 1: Personnel Training and Responsibilities

The accuracy and safety of a nonsterile compound are directly proportional to the skill and diligence of the person preparing it. Chapter <795> places significant emphasis on ensuring that all compounding personnel are properly trained and demonstrate competency.

Core Competencies for Nonsterile Compounding Staff:

• Foundational Knowledge: Staff must read and understand USP <795> and all relevant policies and procedures (P&Ps). This isn’t just a suggestion; it must be documented. As a manager, you should have a signed attestation in each employee’s training file confirming they have read and understood these critical documents.
• Equipment Proficiency: Personnel must be trained on the proper use, calibration, and maintenance of every piece of equipment they will use, from electronic balances and magnetic stir plates to ointment mills and capsule machines. This includes understanding the limitations and precision of each device.
• Compounding Techniques: This is the hands-on skill. Training must cover the full range of techniques required for the types of preparations your pharmacy makes. This includes weighing, measuring, geometric dilution, trituration, levigation, and understanding the principles of creating stable emulsions and suspensions.
• Hygiene and Garbing: Proper hand hygiene is paramount, even in nonsterile compounding, to minimize the bioburden of the final preparation. Personnel must wear clean lab coats or gowns, hair covers, and gloves. These items should be dedicated to the compounding area and not worn in other parts of the pharmacy.

Pillar 2: The Compounding Facility

USP <795> requires a dedicated, well-defined space for nonsterile compounding to prevent cross-contamination and mix-ups with regular dispensing activities. The idea of compounding on the same counter where you fill prescriptions for metformin is strictly prohibited.

Essential Facility Requirements:

• Designated Area: There must be a space specifically for nonsterile compounding. This area should be located away from high-traffic areas, break rooms, and restrooms to minimize contamination.
• Orderly Environment: The space must be clean, well-lit, and maintained in an orderly state. All components, equipment, and supplies should be stored off the floor.
• Control of Temperature and Humidity: The environment should be controlled to be consistent with the storage requirements of the ingredients and the stability of the final products.
• Cleanable Surfaces: All work surfaces must be smooth, impervious, non-porous, and non-shedding to allow for easy cleaning and to prevent the absorption of contaminants. Stainless steel or epoxy-coated surfaces are ideal.
• Dedicated Sink: A sink with hot and cold running water must be readily accessible for hand washing. This sink should be separate from any sinks used for equipment washing if possible.
• Powder Containment: If you are compounding with bulk powders that are not hazardous, you still need a way to control the spread of dust. This can be achieved through careful technique or the use of a powder containment hood (also known as a Class I Biological Safety Cabinet or a Ventilated Compounding Enclosure), though this is not strictly mandated unless required by other regulations or risk assessments.

Pillar 3: Components, Master Records, and Compounding Records

This pillar forms the core of documentation and traceability for nonsterile compounding. It is how you prove that what you intended to make is what you actually made, every single time. As a manager, this is your primary tool for quality assurance and investigation if a problem arises.

Component Selection and Handling:

The quality of your final preparation can be no better than the quality of your starting ingredients. You cannot simply use large stock bottles of medications from your dispensing shelf.

• USP/NF Grade: Whenever possible, all active pharmaceutical ingredients (APIs) and excipients must be of USP or National Formulary (NF) grade.
• Certificate of Analysis (CoA): If USP/NF grade is not available, you must obtain a Certificate of Analysis from the supplier for your chosen ingredient, confirming its identity, purity, and quality. As a manager, you must have a system for receiving, reviewing, and filing these CoAs.
• Labeling and Expiration: All components must be clearly labeled and stored according to manufacturer recommendations. Critically, if a component does not have a manufacturer-assigned expiration date, the pharmacist must assign a conservative one, not to exceed 3 years from the date of receipt, and document the rationale.

Master Formulation vs. Compounding Record: The Recipe vs. The Batch Record

This is a concept that is often confusing but is operationally critical. You must be able to distinguish them clearly.

Element	Master Formulation Record (MFR)	Compounding Record (CR)
Analogy	The Master Recipe Card. This is the official, validated “recipe” for a specific product. It is created once and used every time you make that product.	The Cooking Log for a Specific Batch. This is the detailed log of a single compounding event, documenting exactly what happened when you followed the recipe on a particular day.
Purpose	To ensure consistency and standardization every time a formulation is prepared.	To create a traceable record of a specific preparation, linking it to the exact ingredients, equipment, and personnel involved.
Key Contents	Drug name, strength, and dosage form Calculations needed List of all ingredients and their quantities Compatibility and stability information Equipment needed Step-by-step mixing instructions Assigned Beyond-Use Date (BUD) and its justification Container/closure information Quality control procedures (e.g., pH testing, visual inspection)	Reference to the MFR Names, manufacturers, lot numbers, and expiration dates of all ingredients used Quantities of each ingredient measured Total quantity compounded Name of person who prepared it Name of pharmacist who approved it Date and time of preparation Assigned prescription or lot number The actual BUD assigned Results of any quality control tests performed

Pillar 4: Beyond-Use Dating (BUD)

The BUD is the date after which a compounded nonsterile preparation (CNSP) should not be used. It is determined from the date the preparation is compounded. This is one of the most critical responsibilities of the pharmacist and is based on the ability of the preparation to maintain its chemical and physical stability, potency, and to resist microbial proliferation. A BUD is not the same as a manufacturer’s expiration date. The USP provides default BUD limits in the absence of specific stability studies for the exact formulation.

Masterclass Table: Default BUDs for Nonsterile Preparations (USP <795> 2023)

Formulation Type	Definition & Examples	Storage Condition	Maximum BUD	Scientific Rationale
Non-aqueous Formulations	Formulations where no water is present. This includes powders, capsules, ointments, suppositories, and fixed oils. Examples: Progesterone in oil capsules, Testosterone ointment.	Controlled Room Temperature or Refrigerated	180 days	The absence of water dramatically inhibits microbial growth and slows many chemical degradation pathways, particularly hydrolysis. This is the most stable category of CNSPs.
Water-Containing Oral Formulations	Formulations containing water, typically preserved with an antimicrobial agent. Examples: Most oral suspensions (e.g., Omeprazole suspension), solutions, and emulsions.	Refrigerated (2° to 8°C)	14 days	Water supports microbial growth. Even with preservatives, the potential for contamination and proliferation is significant. Refrigeration is required to slow this growth. The 14-day limit is a conservative timeframe to ensure safety before significant microbial contamination can occur in a preserved system.
Water-Containing Topical/Dermal and Mucosal Liquid and Semisolid Formulations	Formulations containing water for application to the skin, or mucous membranes like nasal or vaginal preparations. Examples: Magic Mouthwash, hydrocortisone cream made from powder, nasal sprays.	Controlled Room Temperature	30 days	These preparations typically have a higher concentration of active ingredients and a lower water activity compared to oral liquids, and are often preserved. This provides slightly more protection against microbial growth than an oral liquid, allowing for a longer room temperature BUD. The 30-day limit balances stability with the risk of contamination from repeated patient use.

13.1.3 Deep Dive: USP General Chapter <797> – Pharmaceutical Compounding – Sterile Preparations

If USP <795> is about ensuring quality and chemical stability, USP <797> is about preventing death. This is not hyperbole. The stakes are raised exponentially when a preparation is designed to be injected directly into a patient’s bloodstream, spinal fluid, or eyes, bypassing all of the body’s natural defenses. A single microbe in a vial of parenteral nutrition can lead to sepsis and death. The historical tragedy of the New England Compounding Center (NECC) in 2012, where contaminated steroid injections led to a nationwide fungal meningitis outbreak that killed over 100 people, serves as a permanent, chilling reminder of why these standards exist and why they must be followed with absolute, unwavering diligence. As a manager, you are the ultimate guardian of the sterile compounding environment. Your primary responsibility is to prevent the introduction of microbial contamination into Compounded Sterile Preparations (CSPs).

Pillar 1: Categories of CSPs and Beyond-Use Dating

The 2023 revision of USP <797> fundamentally changed how CSPs are categorized. The old system of low-, medium-, and high-risk has been replaced by a more logical system based on the conditions under which a CSP is made and the time until it is administered. This is a critical concept for managers to master as it directly dictates your facility requirements and the expiration dating you can assign.

Masterclass Table: Categories of Compounded Sterile Preparations (CSPs)

Category	Compounding Environment	Starting Ingredients	BUD Limits (without sterility testing)	Operational Significance & Managerial Focus
Category 1	Can be prepared in a Segregated Compounding Area (SCA), which is a less stringent, unclassified space containing a Primary Engineering Control (PEC) like a laminar airflow workbench.	Only sterile starting ingredients.	≤ 12 hours at Controlled Room Temp ≤ 24 hours Refrigerated	This category is for preparations needed for immediate or short-term use. It allows for more flexibility in facility design (no full cleanroom required) but imposes very strict, short BUDs. Manager’s Focus: Strict adherence to the 12/24 hour BUD. Ensuring staff understands that a product made in an SCA cannot be used tomorrow if left at room temp. Perfect for small hospitals or clinics preparing STAT drips or OR syringes.
Category 2	Must be prepared in a full Cleanroom Suite (an ISO 7 buffer room with an ISO 8 ante-room) containing a PEC.	Only sterile starting ingredients.	4 days at Controlled Room Temp 10 days Refrigerated 45 days Frozen (BUDs can be extended if preservatives are added or terminal sterilization is performed).	This is the workhorse category for most hospital pharmacies and outsourcing facilities. The investment in a full cleanroom allows for longer BUDs, enabling batch production and more efficient workflow. Manager’s Focus: Maintaining the integrity of the cleanroom suite through rigorous environmental monitoring, cleaning protocols, and staff garbing/aseptic technique competency. This is the gold standard for most CSPs.
Category 3	Must be prepared in a full Cleanroom Suite with additional requirements, including use of sterile gloves and more rigorous cleaning/disinfection.	Can use sterile or nonsterile starting ingredients.	BUDs can be up to 180 days under any storage condition, BUT this is ONLY permissible if: Each batch passes sterility testing. Each batch passes endotoxin (pyrogen) testing. There is valid stability data for the formulation.	This category is for the highest-risk preparations, such as those made from bulk, nonsterile powders, or for large-scale batching intended for long-term storage. This is the domain of large compounding centers and 503B outsourcing facilities. Manager’s Focus: Immense focus on quality control. Managing contracts with external labs for sterility/endotoxin testing, quarantining batches pending results, and maintaining meticulous stability data records. This is a highly specialized and regulated operation.

Pillar 2: The Cleanroom Suite – A Fortress Against Microbes

A cleanroom is not just a clean room; it is an engineered environment designed to control air quality, pressure, temperature, and humidity to minimize the risk of contamination. As a manager, you must understand the function of each component of the suite.

Pillar 3: Gowning, Garbing, and Aseptic Technique

The single greatest source of contamination in a cleanroom is the people working in it. Humans shed millions of particles per minute. Gowning and garbing is a ritualized process designed to contain these particles. Aseptic technique is the disciplined set of behaviors used inside the hood to prevent the transfer of microorganisms from non-sterile surfaces to sterile ones. As a manager, you must enforce a zero-tolerance policy for deviations from these procedures.

The Garbing Sequence (Performed in the Ante-Room):

1. Don Shoe Covers and Hair/Beard Covers: This is done first to contain contamination from the floor and hair.
2. Perform Hand Hygiene: Wash hands and forearms with soap and water for at least 30 seconds.
3. Don Gown: Step into the gown, ensuring it is the appropriate size and covers you from neck to knees.
4. Apply Alcohol-Based Hand Rub: Sanitize hands thoroughly.
5. Don Gloves: The first pair of gloves can be donned in the ante-room. For Category 3 CSPs, sterile gloves must be used and are often donned in the buffer area.
6. Sanitize Gloves: Regularly apply sterile 70% isopropyl alcohol (IPA) to gloves throughout the compounding process.

Aseptic Technique is a skill that must be taught, practiced, and mastered. It includes principles like:

• First Air: Never block the flow of clean HEPA-filtered air from the back of the hood to critical sites (e.g., vial septa, needle hubs). All manipulations must be performed at least 6 inches inside the hood.
• Swabbing Surfaces: All vial stoppers, ampule necks, and injection ports must be swabbed with sterile 70% IPA and allowed to dry before being punctured.
• Proper Needle Handling: Never touch any part of the needle. Do not core vials. Ensure syringes are the correct size to accurately measure the required volume.

Pillar 4: Environmental Monitoring (EM)

How do you know if your fortress is working? You test it. Environmental monitoring is the program used to actively sample the air and surfaces within your compounding areas to quantify the level of microbial contamination. It provides objective data on the state of control of your environment. As a manager, reviewing EM reports is one of your most critical quality assurance functions.

Monitoring Type	Description	Frequency (Minimum)	Managerial Action
Non-Viable Air Sampling (Particle Counts)	An electronic particle counter measures the number of particles of different sizes in the air. This is how you certify that a room is ISO Class 7 or 8.	Every 6 months	Review certification reports. A failure indicates a problem with the HEPA filters or the overall HVAC system and requires immediate engineering intervention.
Viable Air Sampling	An impaction air sampler pulls a specific volume of air over a petri dish (media plate) which is then incubated to see what microorganisms grow.	Every 6 months	Review culture results. Compare the number of colony-forming units (CFUs) to the action levels defined in USP <797>. An excursion requires investigation to identify the cause (e.g., poor cleaning, HVAC issue).
Surface Sampling	Contact plates or swabs are used to sample surfaces inside the PECs, work surfaces, and in the cleanroom. They are incubated to detect microbial contamination.	Monthly	This is your report card on staff technique and cleaning effectiveness. High CFU counts in the PEC point to poor aseptic technique. High counts on counters point to inadequate cleaning. Use these results as a tool for targeted retraining.

13.1.4 Deep Dive: USP General Chapter <800> – Hazardous Drugs – Handling in Healthcare Settings

USP <800> represents a paradigm shift in compounding safety. While <795> and <797> are focused primarily on protecting the patient from the preparation, <800> is focused on protecting the healthcare worker from the drug. This chapter applies to all healthcare personnel who handle hazardous drugs (HDs), including pharmacists, technicians, nurses, and environmental services staff. Its goal is to minimize exposure to drugs that are known or suspected to be carcinogenic, teratogenic, genotoxic, or have other reproductive or organ toxicity at low doses. The safety measures are designed to protect your team from the cumulative effects of years of low-level exposure.

Pillar 1: The NIOSH List and Assessment of Risk (AoR)

The foundation of any <800> compliance program is knowing which drugs are considered hazardous. This is defined by the National Institute for Occupational Safety and Health (NIOSH) List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings.

However, <800> provides an operational flexibility pathway called the Assessment of Risk (AoR). As a manager, this is one of your most important strategic tools. An AoR allows a facility to determine alternative containment strategies and work practices for certain HDs on the NIOSH list. Crucially, an AoR CANNOT be performed for any antineoplastic drug that requires manipulation (e.g., crushing, compounding) or for any API of an HD. For those, all rules of <800> must be followed. An AoR is typically used for lower-risk dosage forms, like tablets or capsules of certain non-antineoplastic HDs.

Pillar 2: Engineering Controls – Containment is Key

For all HDs that require manipulation, <800> mandates a “containment sandwich” of engineering controls to keep hazardous particles and vapors contained and away from staff.

• Containment Primary Engineering Control (C-PEC): This is the hood. For sterile HDs, it’s a Class II Biological Safety Cabinet (BSC). For nonsterile HDs, it’s a Containment Ventilated Enclosure (CVE). It is a ventilated, contained space.
• Containment Secondary Engineering Control (C-SEC): This is the room the C-PEC is in. It must be externally vented, have a specific number of air changes per hour (ACPH), and be physically separated from other areas. For sterile HD compounding, this is the negative pressure ISO 7 buffer room.

Pillar 3: Personal Protective Equipment (PPE)

<800> mandates specific, redundant PPE to provide a final barrier between the worker and the drug. As a manager, you must ensure an adequate supply of this specialized equipment is always available and that staff are trained on its proper use.

PPE Item	Requirement	Rationale
Gloves	Two pairs of ASTM D6978-rated chemotherapy gloves are required for compounding and administering HDs. The outer glove must be sterile for sterile compounding. Gloves must be changed every 30 minutes.	Provides a redundant barrier against permeation and contamination. The specific ASTM rating ensures the gloves have been tested against chemotherapy drugs.
Gowns	Must be disposable, resistant to permeability by HDs, and close in the back. Must be changed per manufacturer’s instructions or if soiled.	Protects the worker’s clothing and skin from splashes and spills. Standard lab coats are not sufficient.
Head, Hair, and Shoe Covers	Two pairs of shoe covers are required when entering the HD buffer room.	Prevents the tracking of HD contamination out of the compounding area.
Eye and Face Protection	Required when there is a risk of splashes or spills (e.g., working outside of a C-PEC, cleaning spills).	Protects mucous membranes from exposure.
Respiratory Protection	Required for tasks like cleaning up large spills, deactivating a C-PEC, or handling HDs without adequate containment. An N95 respirator is usually sufficient.	Protects against inhalation of aerosolized HD particles.

Pillar 4: Decontamination, Cleaning, and Disinfection

Cleaning HD areas is a specific, multi-step process designed to first render any HD residue inert, then remove it, then kill any microorganisms.

1. Decontamination: Applying an agent like bleach or peroxide to deactivate the HD molecule itself.
2. Cleaning: Using a germicidal detergent to remove organic and inorganic material.
3. Disinfection: Applying sterile 70% IPA to kill microorganisms (required for sterile compounding areas).

As a manager, you must develop P&Ps that detail this process and ensure staff (including environmental services personnel) are trained and competent to perform it safely.

13.1.5 The Integrated Compounding Operation: A Manager’s Synthesis

A common mistake is to view these chapters in isolation. In reality, they are an overlapping, integrated system of controls. A modern compounding pharmacy does not just have a “<797> area” or an “<800> area”; it has a comprehensive compounding operation where the principles of all three chapters are applied based on the specific product being made.

The ultimate challenge for an operations manager is to synthesize these requirements into a cohesive workflow. For example, when preparing a sterile hazardous drug like fluorouracil:

• The principles of USP <797> dictate the need for an ISO 7 buffer room, aseptic technique, and proper garbing to ensure the final product is sterile for the patient.
• The principles of USP <800> build upon this, mandating that the ISO 7 buffer room be negative pressure, that the hood be a C-PEC vented externally, and that the staff wear double chemotherapy gloves and a protective gown to ensure their own safety.
• The principles of USP <795>, while less direct, still inform the process through its requirements for staff training documentation, component quality (the sterile diluent used must be of USP grade), and the proper creation of Master Formulation and Compounding Records.