Sterile Compounding Facility and Equipment Materials

OPTIMIZING THE STERILE COMPOUNDING ENVIRONMENT: FACILITY AND EQUIPMENT ESSENTIALS

Faculty:

Liz Fredrickson, PharmD, BCPS

Liz Fredrickson is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy.

Pamela Sardo, PharmD, BS

Pamela Sardo is a freelance medical writer, pharmacist licensed in 3 states, and the founder/principal at Sardo Solutions. She received her BS from the University of Connecticut and a PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, pharmaceutical manufacturing, and managed healthcare across broad therapeutic classes and disease states.

Topic Overview:

Sterile compounding requires thorough attention to facility design, equipment usage, and cleaning protocols to ensure the integrity and safety of compounded sterile preparations (CSPs). This continuing education activity focuses on important considerations pertaining to sterile compounding facilities and equipment, providing pharmacists and pharmacy technicians with essential knowledge and skills to maintain compliance and quality standards.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist 0669-0000-25-012-H07-P

Pharmacy Technician  0669-0000-25-013-H07-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: February 20, 2025 Expiration Date: February 20, 2028

Target Audience: This educational activity is for pharmacists and pharmacy technicians.

Secondary Audiences: Other healthcare professionals, such as nurses, physicians, or others who may be part of a healthcare team, may be interested in this educational topic. Healthcare team roles and approaches to patient care are discussed in this activity. No state board, professional organization, or credentialing body has evaluated this activity to determine whether it meets the continuing education requirements of nurses, physicians, or other professions not listed under the “Target Audience” section above. Always verify with individual employers or supervisors whether they will accept this educational activity upon completion.

How to Earn Credit: From February 20, 2025, through February 20, 2028, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Explain the roles of primary and secondary engineering controls in compounding sterile preparations

Describe important design elements of sterile compounding facilities

Review the processes of using and maintaining cleaning sterile compounding equipment and supplies

Describe agents, supplies, and techniques used for cleaning and sanitizing sterile compounding equipment

Disclosures

The following individuals were involved in developing this activity: Liz Fredrickson, PharmD, and Pamela Sardo, PharmD, BS. Pamela Sardo and Liz Fredrickson, PharmD, BCPS, have no conflicts of interest or financial relationships regarding the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

© RxCe.com LLC 2025: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Educational Activity

Optimizing the Sterile Compounding Environment: Facility and Equipment Essentials

Introduction

Sterile compounding requires thorough attention to facility design, equipment usage, and cleaning protocols to ensure the integrity and safety of compounded sterile preparations (CSPs).1 This continuing education activity focuses on important considerations pertaining to sterile compounding facilities and equipment, providing pharmacists and pharmacy technicians with the essential knowledge to maintain compliance and quality standards.

Overview of Facility Design

Designing a sterile compounding facility requires careful consideration to create a modern, comfortable, functional cleanroom environment. Sterile compounding facilities should be designed, organized, and maintained to support high-quality compounding practices.2 The United States Pharmacopeia, Chapter 797, Pharmaceutical Compounding - Sterile Preparations (USP <797>), provides standards on sterile compounding equipment and facility designs.1 The most recent USP <797> was published in November 2023.1 Table 1 summarizes the differences between the 2008 and 2023 versions.1 It is recommended that all personnel involved with sterile compounding read and be familiar with the revised standards. In addition, it is vital to stay current with the rules and regulations of your local regulatory jurisdiction.

Pause and Ponder

Does the design of your sterile compounding facility comply with USP

<797> standards, and are there any areas for improvement?

Table 1

Comparison of 2008 and 2023 USP <797> Facility and Equipment Standards1,3

To ensure compliance and smooth facility operations, there are several design factors for compounding personnel to consider.1,2,4 These include the following:

Number of compounding personnel

Equipment (PECs, carts, computers), including placement

Workflow/movement of compounding personnel and supplies

Number, type, and complexity of compounding activities that will be performed

Potential for unsanitary conditions (see Table 2)

Table 2

Potential Insanitary Conditions in Sterile Compounding Facilities5

The amount of space needed will depend on the needs of the compounding facility; however, many state boards of pharmacy have minimum requirements for the amount of space needed.6 Only essential furniture, equipment, and materials should be present in classified areas, and they must be low-shedding and easy to disinfect and clean.1 This is because the placement and movement of materials within sterile compounding areas significantly impact air quality.1 Because of this, items such as corrugated cardboard and shipping cartons should not be brought into these areas.1 Additionally, spaces used to prepare CSPs should never be used for processes such as order entry.6

All materials entering the buffer room must be disinfected with sterile 70% IPA to prevent the introduction of contaminants.1 Carts used to transport

materials must be cleaned and disinfected before entering the buffer room. They must not move from the dirty side to the clean side of the anteroom without proper decontamination.1 These measures reduce the risk of cross- contamination and maintain the integrity of the sterile environment.1

Sinks must be accessible for handwashing and located at least one meter from primary engineering controls (PECs) to minimize contamination.6 Stainless steel is the preferred material for sinks due to its durability and ease of cleaning.6 Sinks should also be positioned to support efficient garbing practices without risking splash contamination.6

Air Quality Standards and Environmental Control

Maintaining air quality classifications is a cornerstone of sterile compounding. Doing so minimizes the risk of exposing CSPs to airborne contaminants.1 Studies have consistently shown that breaches in air quality can lead to increased rates of contamination, resulting in potentially life- threatening infections for patients receiving CSPs.7 Air cleanliness is classified according to particle concentration (Table 3).1 These classifications ensure that particulate matter does not compromise the integrity of CSPs.1

Table 3

ISO Classification of Particulate Matter in Rooms Air1

To maximize air quality, compounding facilities must be designed in such a way that the quality of air improves as it moves through operational areas to the PEC. (See Table 4.)1

Table 4

Air Movement Through Operational Areas

Air exchange rates play a critical role in maintaining air quality, and airflow is measured in air changes per hour.1 ISO Class 7 rooms require a minimum of 30 air changes per hour (ACPH), while ISO Class 8 rooms require at least 20 ACPH.1 Air changes per hour needed depend on numerous factors, including the following:

Number of personnel permitted to work in the area

Number of particles that may be generated from activities and processes in the area

Equipment located in the room

Room pressure

Table 5 summarizes ACPH requirements for non-hazardous sterile compounding areas. The air supplied to these rooms must be HEPA-filtered, and a minimum of 15 ACPH must come directly from the HVAC system.1 While these are USP <797> minimum requirements, it is recommended to aim for higher numbers as guidelines can change over time.6 Additionally, with continued use, HEPA filters become less efficient, and ACPH will decrease.6

Table 5

ACHP Requirements1

Continuous monitoring of pressure differentials is also necessary to ensure positive pressure of at least 0.020-inch water column between adjacent ISO-classified areas.1 These measures help prevent contamination from lower-classified or unclassified areas.1

Environmental conditions such as temperature and humidity must also be controlled. The cleanroom suite should be maintained at a temperature of 20°C or cooler and a relative humidity of 60% or lower.1 These parameters reduce microbial proliferation and create a comfortable working environment for personnel.1 Temperature and humidity must be monitored daily or continuously and documented to ensure compliance, and this should be done manually or using a continuous recording device.1 Any adjustments made to these parameters should be documented, and staff should be trained to address any deviations.6 Facilities should avoid introducing additional water sources, such as humidifiers, as they can increase contamination risks.6 Finally, temperature and humidity monitoring devices must be monitored at least every 12 months or sooner if the manufacturer requires.1

Engineering Controls

USP <797> requires the use of primary engineering controls (PEC) and secondary engineering controls (SEC).6 Understanding this terminology and the difference between PECs and SECs is important. PECs are also known as “hoods” and are types of engineering controls, whereas SECs are the rooms in which PECs are placed.6 Rooms or devices deemed “classified” must meet the requirements of the International Organization for Standardization (ISO) standard 14644-1 for air cleanliness. (See Table 6.)6

Table 6

Engineering Controls Classification Requirements1,6

Primary Engineering Controls

Laminar Airflow

Laminar airflow is characterized by uniform, unidirectional airflow that moves at a consistent velocity, reducing turbulence and minimizing the risk of particle contamination.1 Airflow patterns in PECs are carefully designed to sweep particulates away from the critical compounding area, where sterile products are manipulated.1 The air is filtered through high-efficiency particulate air (HEPA) filters, which remove 99.97% of airborne particles ≥0.3

microns.1 The airflow must meet ISO Class 5 standards, and maintaining this level of cleanliness is crucial for preventing microbial contamination.1

In PECs, laminar airflow can be vertical or horizontal:

Vertical Laminar Airflow: Air is drawn from the top of the PEC, passes through a HEPA filter, and moves downward over the compounding area1

Horizontal Laminar Airflow: Air is drawn from the back of the PEC, passes through a HEPA filter, and flows horizontally across the work surface toward the operator1

Laminar Airflow System (LAFS)

A LAFS creates an ISO Class 5 or better environment for sterile compounding by providing unidirectional HEPA-filtered airflow.1 This airflow minimizes contamination risks in the sterile compounding area by protecting the direct compounding area (DCA) from process-generated and external contamination.1

A LAFS must be positioned away from traffic and air currents to maintain proper airflow within the PEC:1

For Category 1 CSPs, an ISO Class 5 PEC can be placed in an unclassified SCA

For Category 2 or 3 CSPs, the LAFS must be within a cleanroom suite with an ISO Class 7 buffer room and an ISO Class 8 anteroom

A dynamic airflow smoke pattern test is required initially and every six months to verify proper placement and ensure compounders maintain unidirectional airflow in the DCA

Types of LAFS include laminar airflow workbenches (LAFW), integrated vertical laminar flow zone (IVLFZ), and class 2 biological safety cabinets (BSC).1 These are described in more detail here in Table 7.

Table 7 Types of LAFS1

Restricted Access Barrier Systems (RABS)

A RABS enclosure provides ISO Class 5 unidirectional HEPA-filtered airflow, minimizing contamination risks.1 It allows controlled ingress and egress of materials through validated openings that remain closed during compounding.1 RABS include Compounding Aseptic Isolators (CAIs) and Compounding Aseptic Containment Isolators (CACIs), which use glove ports to maintain physical separation between the external environment and aseptic manipulations. (See Table 8.)1

Table 8 Description of RABS1

RABS can be used in different environments depending on the category of CSPs being prepared.1 For Category 1 CSPs, RABS may be placed in an unclassified SCA to achieve an ISO Class 5 environment.1 However, for Category 2 or 3 CSPs, RABS must be in a cleanroom suite with an ISO Class 7 buffer room and an ISO Class 8 anteroom.1 The recovery time required to achieve ISO Class 5 air quality after opening the transfer chamber must be documented, typically by the manufacturer, and internal procedures must ensure sufficient recovery time both before and during compounding operations.1 Additionally, dynamic airflow smoke pattern tests must be conducted initially and every six months under dynamic operating conditions to confirm proper integration of the RABS into the facility and to ensure compounders can effectively use unidirectional airflow to maintain ISO Class 5 conditions in the DCA.1

Secondary Engineering Controls

Cleanroom Suite

The design of a sterile compounding facility must accommodate adequate space for equipment, workflow, and future expansion.6 Classified compounding areas must have smooth, impervious, non-shedding surfaces on ceilings, walls, floors, doors, fixtures, and cabinetry to allow effective cleaning and minimize contamination risks.1 These surfaces should resist damage from cleaning agents and disinfectants. All junctures between walls, floors, and ceilings must be sealed, and inlaid ceiling panels must be caulked to their frames.1 Walls should be durable and seamlessly constructed or coated, and floors should either be coved to the walls or caulked at the junction.1 The design should avoid dust-collecting ledges or overhangs, and any present must be easy to clean.1 Ceiling light fixtures should be smooth, flush- mounted, and sealed, with any penetrations through ceilings or walls also sealed to maintain cleanliness.1

A cleanroom suite must include an anteroom and at least one buffer room, with both rooms requiring HEPA-filtered ceiling air and ISO classification. The buffer room is where CSPs are compounded.1 Activities in

this room must be controlled to prevent particulate generation and maintain air quality.1 Adjacent to the buffer room is the anteroom, which serves as a transitional space for hand hygiene, garbing, and staging of materials, with a clear demarcation line separating the "clean" and "dirty" sides.6 The clean side is the one closest to the buffer room.1 Facilities could also choose to have a dirty and clean anteroom, with the clean anteroom closest to the buffer room.1 Movement between rooms of differing ISO classifications must also be carefully controlled.1 Airlocks and interlocking doors can help maintain pressure differentials and air quality.1 Positive pressure is maintained in the anteroom to prevent contamination from adjoining spaces.6

Anterooms and buffer rooms must be kept separate from any surrounding, unclassified areas by fixed walls and doors.1 SCA can suffice for smaller operations but must be separated by a visible perimeter.6 Plastic curtains or other makeshift barriers are discouraged as they are difficult to clean and maintain.6 Sterile compounding facilities require strict control of dynamic interactions between rooms to maintain proper airflow and classification.1 Key considerations include the following:

The placement and movement of doors, avoiding seals or sweeps between buffer and anterooms, and using hands-free access doors

Avoiding the use of tacky mat in ISO-classified areas

For facilities compounding both sterile and nonsterile preparations, keeping the respective PECs in separate rooms unless the room can continuously meet ISO Class 7 standards

Special Considerations for Segregated Compounding Areas (SCAs)

SCAs are an alternative to cleanroom suites for compounding Category 1 CSPs.1 In these areas, PECs provide ISO Class 5 conditions but are located in unclassified spaces.1 These areas must be clearly defined by visible perimeters or housed in separate rooms.6 Hazardous drugs cannot be compounded in SCAs, but containment SCAs (C-SCAs) may be used for some hazardous compounding if they meet USP <800> requirements for negative pressure and 12 ACPH.6 The placement of SCAs must consider environmental

control challenges, such as proximity to high-traffic areas or sources of contamination.1

The SCA and its surfaces (walls, floors, counters, and equipment) must be clean, uncluttered, and solely used for compounding.1 Surfaces should be smooth, impervious, non-shedding, and resistant to damage from cleaning agents and disinfectants.1 They must be easy to clean and designed to minimize contamination risks. Dust-collecting features like overhangs and ledges should be avoided or made easily cleanable.1

Although SCAs offer flexibility, they require strict adherence to environmental control measures to ensure the safety and efficacy of CSPs.1 Personnel must be vigilant in following hygiene and garbing protocols and must regularly monitor air and surface quality.1

Certification and Recertification Requirements

Certification and recertification of sterile compounding facilities are critical for verifying compliance with USP <797> standards. Initial certification must be performed before the facility is operational, and recertification must occur at least every six months or whenever significant changes are made to the facility or equipment.1 Certification ensures that the facility meets design and air quality specifications through a series of tests.1 Facilities must document all certification and recertification records, including the number of personnel present during testing, and implement corrective actions for any deficiencies identified.1 This documentation ensures accountability and facilitates continuous improvement.1

Table 9, below, details various testing requirements that should occur within facilities.1 These assessments provide a comprehensive evaluation of the facility’s performance under dynamic operating conditions.

Table 9 Testing Requirements1

Cleaning, Disinfecting, and Microbial Monitoring

Proper cleaning and disinfection are vital for maintaining the sterile environment required for CSP preparation. (See Tables 10 and 11.) Surfaces must be cleaned to remove organic and inorganic materials, disinfected to destroy microorganisms, and treated with sporicidal agents to eliminate bacterial and fungal spores.1

In PECs, sterile 70% IPA is applied after these steps to remove residues and before and during compounding to minimize contamination.1 Cleaning and disinfection should follow written SOPs, use sterile supplies, and be documented.1 All compounding personnel must follow established protocols, ensure proper contact times for agents, and document all procedures.1

Microbial monitoring of air and surfaces is equally important for assessing environmental quality.1 Viable air sampling must be performed every six months for Category 1 and 2 CSPs and monthly for Category 3 CSPs.1 Sampling sites should include locations at greatest risk of contamination, such as PECs and frequently touched surfaces. Surface sampling must be conducted at least monthly and immediately following any incidents that could compromise sterility.1 Any microbial growth exceeding action levels must trigger a thorough investigation and corrective actions,

including process improvements, personnel retraining, or HEPA filter maintenance.1

Table 10

Purposes of Cleaning, Disinfectant, and Sporicidal Agents

Table 11

Recommended Frequency of Cleaning and Disinfecting in the Sterile Compounding Environment

Sterile Compounding Equipment

Equipment used to prepare CSPs can be broadly categorized into four groups based on function.2 The first category includes tools used directly in compounding, such as ampule openers, vacuum pumps, sterile filtration equipment, and sterile spatulas and spoons.2 The second group encompasses quality control devices, such as particle counters, pyrogen testing materials,

and sterility testing equipment.2 Storage and delivery items form the third category, including refrigerators, automobile-compatible coolers and heaters, and ice replacement gels.2 Finally, cleanroom maintenance equipment includes personnel apparel, cleaning materials, HEPA filters, and robotic systems designed to maintain a sterile environment.2

Refrigerators and freezers are permitted within sterile compounding areas but must be medical-grade and strategically placed to minimize particle generation.6 Solid-state refrigerators-which lack compressors-are recommended to reduce particulate contamination.6 Pass-through refrigerators are prohibited in negative pressure rooms.6 Additional equipment such as repeater pumps, automated compounding devices, and printers may be used, provided they do not compromise air quality.6 Certification and environmental monitoring should include these items to ensure compliance under dynamic conditions.6 General and advanced sterile compounding equipment is listed in Table 12.

Table 12

General and Advanced Sterile Compounding Equipment2

Compliance Checklist for Maintaining Sterile Compounding Facilities

To ensure compliance with USP <797>, facilities must implement the following measures:1,6

Maintain air quality through appropriate PECs and SECs.

Monitor environmental conditions, including air exchange rates, pressure differentials, temperature, and humidity.

Certify and recertify facilities and equipment at least every six months.

Implement rigorous cleaning, disinfection, and microbial monitoring protocols.

Control the placement and movement of materials and equipment to minimize contamination risks.

Establish comprehensive Standard Operating Procedures (SOPs) for all activities related to sterile compounding.

Summary

Sterile compounding facilities are designed to create controlled environments that safeguard the integrity of CSPs and protect patient safety. Adherence to USP <797> guidelines for facilities and equipment ensures compliance with the highest standards of sterility and quality. Compounding personnel can minimize contamination risks and uphold the trust in their services by understanding facility design principles, air quality maintenance, and environmental monitoring. This comprehensive approach to sterile compounding is essential for ensuring the delivery of safe and effective medications.

Course Test

What is the primary purpose of Primary Engineering Controls (PECs) in sterile compounding?

To provide HEPA-filtered air and create an ISO Class 5 environment for CSP preparation

To ensure positive pressure is maintained between cleanroom suites.

To prevent contamination by maintaining ISO Class 7 conditions in buffer rooms

To facilitate personnel movement in and out of cleanroom suites

Which of the following is a critical design element in sterile compounding facilities?

Placing sinks inside the buffer room for easy access

Using corrugated cardboard for material transport in ISO areas

Sealing junctures between walls, floors, and ceilings to eliminate cracks

Allowing flexible curtains to separate classified and unclassified areas

Which of the following steps is required when transporting materials into the buffer room?

Disinfect materials with sterile 70% IPA before entry

Clean the cart after transferring materials to the buffer room

Store unused supplies temporarily in the anteroom

Use cardboard boxes to protect supplies during transport

What is the purpose of using sporicidal agents in sterile compounding areas?

Remove dirt and debris from surfaces

Destroy bacterial and fungal spores on surfaces

Reduce the number of airborne particulates in ISO7 areas

Sanitize equipment and supplies without leaving residues

Which of the following is the required ISO classification for an Integrated Vertical Laminar Flow Zone (IVLFZ) within an ISO Class 7 buffer room with unidirectional HEPA airflow over worktables and air returns?

ISO Class 5

ISO Class 6

ISO Class 7

ISO Class 8

Which of the following best describes Secondary Engineering Controls (SECs)?

SECs include devices like laminar airflow workbenches that create a sterile environment

SECs include rooms housing PECs that ensure appropriate air cleanliness

SECs include equipment used to sanitize the ISO Class 5 area

SECs include processes that verify the sterility of compounded preparations

Where should the sink be placed in relation to the PEC?

Inside the buffer room for easy access

At least one meter away to minimize contamination risks

Directly adjacent to the PEC for efficient workflow

Outside the anteroom to prevent splashing

How often must HEPA filter integrity testing be conducted in sterile compounding facilities?

Monthly

Every 6 months

Annually

Weekly

What is the primary function of 70% sterile isopropyl alcohol (IPA) in PECs?

To remove bacterial spores from surfaces

To act as a detergent for cleaning debris

To minimize contamination by disinfecting surfaces and removing residues

To sterilize supplies before compounding

How often should sporicidal agents be applied to PEC surfaces for Category 1 and 2 CSPs?

Daily

Weekly

Monthly

Annually

References

United States Pharmacopeia. USP General Chapter <797>: Pharmaceutical Compounding—Sterile Preparations. United States Pharmacopeial Convention; 2023.

Allen LV Jr. The Art, Science, and Technology of Pharmaceutical Compounding. 6th ed. Washington, DC: American Pharmacists Association; 2020.

American Society of Health-System Pharmacists. USP <797>: Key Changes. 2023. https://www.ashp.org/-/media/assets/pharmacy- practice/resource-centers/compounding/docs/USP-797-Key-Changes.pdf. Accessed January 10, 2025.

Wolters Kluwer. 7 USP <797> clean room guidelines you need to know. 2024. https://www.wolterskluwer.com/en/expert-insights/7-usp-797-

clean-room-guidelines-you-need-to-know. Accessed January 10, 2025.

U.S. Department of Health and Human Services, U.S. Food and Drug Administration. Insanitary Conditions at Compounding Facilities: Guidance for Industry. FDA. 2020. https://www.fda.gov/media/124948/download. Accessed January 10, 2025.

Kienle P. The Chapter <797> Answer Book. 2nd ed. American Society of Health-System Pharmacists; 2023.

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses is constantly changing. Any person taking this course understands that such person must make an independent review of medication information prior to any patient assessment, diagnosis, treatment, and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

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© RxCe.com LLC 2025: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.