USP Chapter 800: Handling Hazardous Drugs in Healthcare Settings
The new USP Chapter 800 provides best practices for all processes related to hazardous drugs (HDs) in healthcare settings. The chapter details the requirements for all aspects of handling hazardous drugs such as storage, mixing, preparing, compounding, dispensing and administration. Chapter 800 provides standards and guidelines for protecting patients, health-system personnel and the environment.
USP 800 defines hazardous drugs as those having one or more of the following criteria:
USP 800 guidelines apply to all personnel who compound hazardous drugs. These include hospital and healthcare pharmacists, pharmacy technicians, physicians, veterinarians as well as other healthcare technicians and assistants involved with compounding or other processes related to hazardous drugs. The standards apply to any facilities where hazardous drugs are prepared which include hospital and healthcare pharmacies, clinics, doctor and veterinarian offices, as well as other locations where hazardous drugs are stored, transported, processed and administered.
According to The United States Pharmacopeia Chapter 800, “there is no acceptable level of personnel exposure” to hazardous drugs. The new chapter defines processes that are intended to provide containment of hazardous drugs “to as low a limit as reasonably achievable”. Furthermore, USP 800 guidelines specify that hazardous materials must be compounded within the proper work environment and equipment. These standards apply to both sterile and nonsterile products and preparations. USP 800 is not intended to replace previous USP chapters that relate to compounding such as USP 795 ‘Pharmaceutical Compounding – Nonsterile Preparations’ and ‘797 Pharmaceutical Compounding – Sterile Preparations’. If a conflict exists between the standards, “the most stringent requirements prevail”.
USP Chapter 800 specifies a wide range of new protocols and procedures as well as facility design and engineering controls. According to USP 800, hazardous drugs (HDs) “shall be handled under conditions that promote patient safety, worker safety, environmental protection, and infection prevention. Manipulation of HDs requires appropriate administrative controls, PPE, engineering and environmental controls, and work practices.” Where facility requirements in Chapter 800 differ from those in USP 797, guidelines for the harmonization of the chapters are provided. Most notably, hazardous drug compounding must be conducted in separate designated areas, with specified ISO classifications. Additional information can be found on the USP website.
Compounding Equipment Guidelines for USP 800
USP 800 describes the proper selection of compounding equipment as well as placement within the designated work zone. The chapter refers to two general types of equipment:
Primary Engineering Controls (PEC): Equipment that is ventilated and provides a prescribed work environment. This includes a comprehensive range of equipment for handling drugs. Basic Primary Engineering Controls may simply facilitate product protection while others, namely Containment Primary Engineering Controls (C-PECs), are designed to protect the operator and environment.
Containment Primary Engineering Controls (C-PEC): Ventilated equipment that is designed and engineered to allow for the safe compounding of hazardous drugs. Containment Primary Engineering Controls prevent exposure to hazardous drugs by integrating the required air handling systems and controls; containment/enclosure systems; filtration and exhaust systems that are specified for the compounding application.
C-PEC equipment may include:
Class II Type A Biological Safety Cabinets may not be used for handling highly volatile toxic chemicals or volatile radionucleotides. Ducted cabinets such as Class II, Type B2 Biological Safety Cabinets are typically used for working with these agents.
NOTE: Laminar Flow Hoods / Laminar Airflow Workbenches (LAFW) are designed for providing product protection only. These units must never be utilized for processing hazardous drugs.
USP 800 – Equipment for Nonsterile Compounding Nonsterile hazardous drugs must be processed in a room that is separate from sterile processes, has 12 air changes per hour (ACPH), and maintains a negative pressure of at least 0.01 inches of water column relative to all adjacent spaces. HEPA filtration may not be required if the hazardous drugs are handled exclusively in a Containment Primary Engineering Control (C-PEC). These ventilated enclosures operate under negative-pressure. C-PECs for nonsterile compounding may include: Class I Biological Safety Cabinets (BSC) and Containment Ventilated Enclosures (CVE).
A Class II Biosafety Cabinet or Compounding Aseptic Containment Isolator (CACI) may be utilized for nonsterile compounding when dedicated solely for compounding nonsterile drugs. However, a Class II BSC or CACI may be used for occasional nonsterile compounding if the equipment is thoroughly disinfected before handling sterile agents.
USP 800 – Equipment for Sterile Hazardous Drug Compounding
USP 800 provides guidelines for the range of facility and equipment configurations for sterile hazardous drug compounding. The standards vary depending on factors such as: hazard level of drugs; sterile-to-sterile or nonsterile-to-sterile processes; the ISO classification and air changes per hour within the compounding room; type of compounding equipment (primary engineering control) utilized.
USP 800 – Configurations for Sterile-to-Sterile Hazardous Drug (HD) Compounding
Configuration 1 – Compounding Sterile HD in a Cleanroom: A Biological Safety Cabinet (BSC) or Compounding Aseptic Containment Isolator (CACI) is utilized as the Containment Primary Engineering Control (C-PEC). Compounding is conducted in an ISO 7 Cleanroom having HEPA supply with 30 air changes per hour (ACPH) and maintains a negative pressure of at least 0.01 inches of water column relative to all adjacent spaces.
Configuration 2 – Compounding Sterile HD using CACI:
A Compounding Aseptic Containment Isolator (CACI) that meets all USP 797 requirements must be utilized. Compounding is conducted in a Containment Segregated Compounding Area (C-SCA) with 12 air changes per hour and maintains a negative pressure of at least 0.01 inches of water column relative to all adjacent spaces. This area does not need to meet ISO Class 7 nor have HEPA-filtration of the room air.
Configuration 3 – Compounding Sterile HD in a BSC:
A Biological Safety Cabinet is utilized for compounding low-to-medium risk hazardous drugs. Compounding is conducted in a Containment Segregated Compounding Area (C-SCA) with 12 air changes per hour and maintains a negative pressure of at least 0.01 inches of water column relative to all adjacent spaces. This area does not need to meet ISO Class 7 nor have HEPA-filtration of the room air. Sterile preparations compounded using configuration 3 may have a more restricted beyond-use date of 12 hours or less. It is also important to note that this configuration may not be used for high-risk sterile hazardous drug compounding.
The configurations for sterile-to-sterile hazardous drug compounding also incorporate relevant design criteria that are specified in USP Chapter 797. For complete details please visit the USP website for these chapters.
USP 800 – Configurations for Nonsterile-to-Sterile Hazardous Drug (HD) Compounding
Configuration 1 – Compounding in an ISO Class 7 Cleanroom:
When compounding nonsterile-to-sterile (high-risk) preparations, the preferred configuration is the placement of compounding equipment in an ISO Class 7 cleanroom.
Configuration 2 – Compounding in area not meeting ISO Class 7:
When compounding in a room that does not meet ISO Class 7, the beyond-use date of compounded sterile preparations may be impacted, depending on what equipment (C-PEC) is utilized. If a Compounding Aseptic Containment Isolator (CACI) meeting all requirements is used, the beyond-use date may not be impacted.
Facilities Compounding Both Nonsterile and Sterile HDs:
Compounding equipment must be located in separate, segregated rooms when compounding both nonsterile and sterile HDs. However, this may not be necessary if the appropriate equipment (C-PEC) that is used for nonsterile products aids to maintain the ISO 7 air quality of the room during nonsterile processes.
For further details about USP Chapter 800 please visit the official USP webpage.