Frequently Asked Questions: <800> Hazardous Drugs—Handling in Healthcare Settings

The following are responses provided by members of the USP Compounding Expert Committee. Responses have been provided for informational purposes only, and should not be construed as an official interpretation of USP text or relied on to demonstrate compliance with USP standards or requirements. 


 

General


 
  1. What is a hazardous drug?
    A hazardous drug is any drug identified as hazardous or potentially hazardous by the National Institute for Occupational Safety and Health (NIOSH) on the basis of at least one of the following six criteria: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity in humans, organ toxicity at low doses in humans or animals, genotoxicity, and new drugs that mimic existing hazardous drugs in structure or toxicity. NIOSH maintains a list of antineoplastic and other hazardous drugs used in healthcare settings.
     
  2. What is the purpose of this chapter?
    The purpose of the chapter is to describe practice and quality standards for handling hazardous drugs in healthcare settings and help promote patient safety, worker safety, and environmental protection. The chapter defines processes intended to minimize the exposure to hazardous drugs in healthcare settings. The chapter was developed by the USP Compounding Expert Committee with the assistance of the USP Compounding with Hazardous Drugs Expert Panel and government liaisons from the U.S. Food and Drug Administration (FDA) and the U.S. Centers for Disease Control and Prevention (CDC) including NIOSH. The chapter was published for the first time for public comment in March 2014. Based on the public comments received, the chapter was revised and proposed for another round of public comments in December 2014. The chapter was revised again and published in the USP-NF in February 2016.
     
  3. Who enforces the chapter?
    The enforcement of USP standards depends on local, state, and federal regulatory agencies.  Accrediting bodies like The Joint Commission survey for compliance with USP compounding standards.  The CMS State Operations Manual, which is used by surveyors to ensure that all of the Conditions of Participation are being met, includes references to USP standards.  Additionally, many state pharmacy practice acts have included references to USP compounding standards.  Each professional licensing board also has the ability to enforce the regulations of that state, which may include USP compounding standards.
     
  4. Who does the chapter apply to?
    Chapter <800> was written to protect all workers, patients and the general public who may be accessing facilities where hazardous drugs (HDs) are prepared. This includes but is not limited to pharmacists, technicians, nurses, physicians, physician assistants, home healthcare workers, veterinarians, and veterinary technicians. If any workers come in contact with HDs, they must receive HD training, and be assessed for an understanding of the training.  All personnel who handle HDs are responsible for understanding the fundamental practices and precautions and for continually evaluating these procedures and the quality of final HDs to prevent harm to patients, minimize exposure to personnel, and minimize contamination of the work and patient-care environment.
     
  5. What settings does the chapter apply to?
    The chapter applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs (e.g., pharmacies, hospitals and other healthcare institutions, patient treatment clinics, physicians' practice facilities, or veterinarians' offices).
     
  6. Does the chapter apply to administration of HDs?
    Yes, the chapter applies to administration of HDs. If non-antineoplastic or reproductive risk HD dosage forms do require manipulation such as crushing tablet(s) or opening capsule(s) for a single dose, alternative containment strategies and work practices as defined in the assessment of risk must be used (e.g. appropriate personnel protective equipment (PPE), use a plastic pouch to contain any dust or particles generated). If antineoplastic HD dosage forms require manipulation, the requirements of Chapter <800> must be followed.
     
  7. What is the status of the General Chapter <800> and when will General Chapter <800> become official?
    General Chapter <800> was published on February 1, 2016 in the First Supplement to USP 39–NF 34. The USP Compounding Expert Committee approved a delayed official implementation date of July 1, 2018 to allow entities additional time to implement the standard. With the delayed official date, entities have more than two years to implement this new standard.
     
  8. Will there be updates or changes to the chapter?
    The final version of the chapter was published on February 1, 2016.  An erratum was published on May 26, 2016 to remove the requirement that the Containment Secondary Engineering Control (C-SEC) be externally vented through high-efficiency particulate air (HEPA) filtration.  This revision does not remove the requirement that the C-SEC be externally vented.  
     
  9. How can I obtain a copy of General Chapter <800>?
    General Chapter <800> was published on February 1, 2016 in the First Supplement to USP 39–NF 34. You may purchase the chapter through a subscription to the USP Compounding Compendium or USP-NF.
     
  10. Have there been any documented/published studies involving harm related to handling of HDs?
    Yes, there are several studies demonstrating risks associated with handling HDs. Some of references are included in the References section of the chapter.

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Personnel


 
  1. Where does the designated person obtain training? How much training does the designated person need?
    Any training should begin with reading the chapter in it is entirety.  All of the requirements for HD handling are defined in the chapter and the chapter provides many references to other source documents.  If additional training is required, many professional organizations conduct training and continuing education programs on the subject. The chapter does not specify a minimum number of training hours.  The designated person must have a thorough understanding of the standards to be able to develop and implement appropriate procedures; oversee entity compliance with the chapter and other applicable laws, regulations, and standards; ensure competency of personnel; and ensure environmental control of the storage and compounding areas.

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Facilities and Engineering Controls


 
  1. Are there requirement for posting signs that HDs are being handled in the facility?
    Signs are not required to be posted at the entrance of facilities. However, signs designating the hazard must be prominently displayed before the entrance to the HD handling areas.  Additionally, signs must be available for restricting access to areas where HD spills occur.
     
  2. Can sterile and nonsterile HDs be stored together?
    See Section 5.2 of the Chapter for guidance on storage.  Sterile and nonsterile HDs may be stored together, but HDs used for nonsterile compounding should not be stored in areas designated for sterile compounding to minimize traffic into the sterile compounding area.  Antineoplastic HDs requiring manipulation other than counting or repackaging of final dosage forms and any HD active pharmaceutical ingredient (API) must be stored separately from non-HDs in a manner that prevents contamination and personnel exposure. These HDs must be stored in an externally ventilated, negative-pressure room with at least 12 air changes per hour (ACPH).   Non-antineoplastic, reproductive risk only, and final dosage forms of antineoplastic HDs may be stored with other inventory if permitted by entity policy.  Refrigerated antineoplastic HDs must be stored in a dedicated refrigerator in a negative pressure area with at least 12 ACPH [e.g., storage room, buffer room, or containment segregated compounding area (C-SCA)].
     
  3. Can refrigerated non-antineoplastic HDs be stored with antineoplastic HDs?
    Yes, a refrigerator must be dedicated to HD storage and located in a negative pressure room with at least 12 ACPH.  Refrigerated antineoplastic HDs must be stored in this dedicated refrigerator.  HD APIs requiring refrigeration must also be stored according to the Chapter.  Other HDs may be stored in this dedicated refrigerator or may be stored with other inventory if an assessment of risk has been performed and implemented.
     
  4. Where should the sink be located?
    Care must be taken to locate water sources and drains in areas where their presence will not interfere with required ISO classifications. Water sources and drains must be located at least 1 meter away from the Containment Primary Engineering Control (C-PEC).  Within an ISO classified area, a hand-washing sink must be placed in the ante-room at least 1 meter from the entrance to the HD buffer room to avoid contamination migration into the negative pressure HD buffer room.  Within an unclassified C-SCA, a hand-washing sink must be placed at least 1 meter from C-PEC and may be either inside the C-SCA or directly outside the C-SCA.
     
  5. Is the C-PEC used for sterile compounding required to be exhausted to the outside or can the C-PEC be recirculated into the negative pressure C-SEC which is exhausted to the outside of the building?
    The Chapter requires that all C-PECs used for manipulation of sterile HDs must be externally vented. Sterile HD compounding must be performed in a C-PEC that provides an ISO Class 5 or better air quality, such as a Class II or III biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI). Class II BSC types A2, B1, or B2 are acceptable.  C-PECs used for pre-sterilization procedures such as weighing and mixing must be either externally vented (preferred) or have redundant–HEPA filters in series and must provide personnel and environmental protection, such as a Class I BSC or Containment Ventilated Enclosure (CVE). A Class II BSC or a CACI may also be used.
     
  6. Can non-HDs and HDs be compounded in C-PECs located in the same C-SEC?
    Separate rooms (C-SECs) are required for sterile, nonsterile, HD and non-HD compounding with two exceptions:

    (1)   Per section 5.3 Compounding, for entities that compound both nonsterile and sterile HDs, the respective C- PECs must be placed in separate rooms, unless those C-PECs used for nonsterile compounding are sufficiently effective that the room can continuously maintain ISO 7 classification throughout the nonsterile compounding activity. If the C-PECs used for sterile and nonsterile compounding are placed in the same room, they must be placed at least 1 meter apart and particle-generating activity must not be performed when sterile compounding is in process; and

    (2)   Per section 5.3.2 Sterile Compounding, a BSC or CACI used for the preparation of HDs must not be used for the preparation of a non-HD unless the non-HD preparation is placed into a protective outer wrapper during removal from the C-PEC and is labeled to require PPE handling precautions.
     
  7. Can a Laminar Airflow Workbench (LAFW) or compounding aseptic isolator (CAI) be used for compounding a non-antineoplastic HD?
    Section 5.3.2 specifies that a LAFW cannot be used for compounding an antineoplastic HD. However, for handling non-antineoplastic and reproductive risk HDs, each facility may conduct an assessment of risk and implement strategies different than those required in the chapter. A LAFW does not provide any protection for the worker from the HD. A LAFW or CAI may be used for non-antineoplastic HDs, however, alternative containment strategies and/or work practices must be determined during the assessment of risk. 
     
  8. Can a BSC or CACI used for compounding HDs be used for compounding non-HDs?
    If a non-HD is prepared in a C-PEC where HDs have been prepared, then the non-HD should be handled and labeled as an HD. The non-HD preparation should be placed into a protective outer wrapper during removal from the C-PEC and should be labeled to require PPE handling precautions. All associated materials and wrappers should be discarded as HD waste because the preparation and associated materials have potentially been contaminated by exposure to HDs.
     
  9. Are closed-system drug-transfer devices (CSTDs) required for compounding HDs?
    No, the Chapter does not require a CSTD for compounding HDs, although it is recommended. However, the Chapter does require that CSTDs be used when administering antineoplastic HDs when the dosage form allows.
     
  10. Is there an evaluation tool one can use for evaluating the performance of the different CSTDs available?
    NIOSH created a draft performance standard protocol for the containment-type CSTDs.  This proposed protocol was published in the Federal Register on September 8, 2015. Five CSTDs were tested by NIOSH and two showed test substance concentration levels below the limit of detection meaning that only 2 of the 5 CSTDs evaluated prevented escape of vapors of the test substance.  The protocol has not been released in final form. 
     
  11. How can a CSTD be chemically incompatible with a HD?
    Depending on the chemical composition of the drug being compounded and the composition of the CSTD device, chemical incompatibilities may exist.  In March 2015, FDA warned against the use of bendamustine with CSTDs, syringes, and adapters containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).  The component in bendamustine (N, N-dimethylacetamide (DMA)) dissolved the ABS or polycarbonate on contact.
     
  12. What is meant by "fixed walls"?
    Fixed walls are solid hard wall modular or ‘stick-build’ construction. According to the Chapter, fixed walls are required to prevent the egress of HD contamination from the C-SEC (either a C-SCA or HD buffer room) as well as ingress of contamination into the ISO Class 7 HD buffer room.
     
  13. Are pressure gauges required to monitor the pressure differential between the C-SEC and the adjacent areas?
    The entity must be compliant with the appropriate USP standards for compounding including <795> and/or <797> and in accordance with applicable federal, state, and local regulations.  Presence of a pressure gauge and at least daily monitoring is currently required for sterile compounding per USP <797>. However, pressure monitoring is not addressed in nonsterile compounding per USP <795>, so entities should follow applicable federal, state, and local regulations. Presence of a pressure gauge and at least daily monitoring of negative pressure storage areas and nonsterile compounding areas helps ensure pressure requirements are continually maintained in these areas.

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Environmental Quality And Control


 
  1. Is environmental wipe sampling required?
    No. The chapter recommends but does not require the performance of environmental wipe sampling. Some common marker HDs that can be assayed include cyclophosphamide, ifosfamide, methotrexate, fluorouracil, and platinum-containing drugs.  If no wipe sampling kit is available for the specific HDs used by the entity, the performance of environmental wipe sampling would not be appropriate.
     
  2. Why is environmental wipe sampling recommended when there is currently no standard for acceptable limits on HD surface contamination?
    Environmental wipe sampling for HD surface residue should be performed to verify containment. Contamination in any amount indicates a lack of containment.  Wipe sampling kits need to be evaluated to ensure they are appropriate for HDs used by the entity. If contamination is found, the chapter states that the designated person must identify, document, and contain the cause of contamination. Such action may include reevaluating work practices, re-training personnel, performing thorough deactivation, decontamination, cleaning, and improving engineering controls. Repeat the wipe sampling to validate that the deactivation/decontamination and cleaning steps have been effective.
     
  3. Does every area where HDs are handled require environmental sampling?
    The chapter recommends, but does not require, the performance of environmental “wipe sampling.”  The term “sampling” indicates that a portion, or sample, of the entire population be tested.
     
  4. What are the acceptable limits for HD surface contamination?
    There is currently no standard for acceptable limits for HD surface contamination. Contamination in any amount indicates a lack of containment and must be addressed.

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Personal Protective Equipment (PPE)


 
  1. Are compounders required to remove all PPE when leaving the compounding area?
    Yes, all PPE would need to be removed when leaving the HD compounding area.  The goal is to contain all hazardous contamination within the negative pressure room.
     
  2. Can gowns be re-worn during the same day if a compounder leaves the HD compounding area?
    Disposable PPE must not be re-used.  Consider all PPE worn when handling HDs to be contaminated with, at minimum, trace quantities of HDs. PPE must be placed in an appropriate waste container and further disposed of per local, state, and federal regulations. PPE worn during compounding should be disposed of in the proper waste container before leaving the C-SEC.
     
  3. What documentation is required to show that a gown will resist permeability by HDs?
    Gowns used for HD handling must be shown to resist permeability by HDs which can be determined by testing against ASTM F739-12. Manufacturers of gowns used for handling HDs should provide results of ASTM F739-12 testing. The gown manufacturer should be able to provide permeability data for commonly used HDs.

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Compounding


 
  1. Is an entity required to have two sets of equipment, one set for compounding HDs and another second set for compounding non-HDs?
    General Chapter <800> states that “disposable or clean equipment for compounding (such as mortars and pestles, and spatulas) must be dedicated for use with HDs.”  This refers to equipment (or parts of equipment) that comes in direct contact with HDs.  Equipment that does not come in direct contact with HDs may be shared between HD and non-HD compounding areas provided it is deactivated, decontaminated and cleaned before it is removed from the HD area.  Equipment used in HD compounding must be operated in the C-SEC unless it is operated as a closed system (e.g. certain mixers, terminal sterilization using an autoclave or convection oven).
     
  2. During nonsterile compounding with HD APIs, are all steps of the compounding process required to be performed in the C-PEC?
    General Chapter <800> states that “bulk containers of liquid and API HD must be handled carefully to avoid spills. If used, APIs or other powdered HDs must be handled in a C-PEC to protect against occupational exposure, especially during particle-generating activities (such as crushing tablets, opening capsules, and weighing powder).” It is recognized that under some circumstances, it is not possible to perform all steps of the compounding process in the C-PEC (e.g. due to equipment size or function).  It is important for the safety of personnel that powdered HDs be weighed and mixed to the wet stage or made into capsules in the C-PEC.  Once nonvolatile, non-antineoplastic, powdered HDs are wet, an assessment of risk may be performed to determine alternative containment strategies and/or work practices.  The NIOSH list of antineoplastic and other HDs provides general guidance on PPE for possible scenarios that may be encountered in healthcare settings including instances where a C-PEC cannot be used.
     
  3. Where should HD APIs be handled prior to sterilization when compounding sterile HDs?
    In addition to <800>, sterile compounding must follow standards in <797> which states that presterilization procedures for high-risk level CSPs, such as weighing and mixing, shall be completed in no worse than an ISO Class 8 environment.  Per <800>, presterilization procedures for high-risk level HD CSPs can occur in the HD ISO Class 7 negative pressure buffer room if the C-PEC used for the nonsterile presterilization procedures is sufficiently effective that the room can continuously maintain ISO 7 classification.  If the C-PECs used for sterile and nonsterile compounding are placed in the same room, they must be placed at least 1 meter apart and particle-generating activity must not be performed when sterile compounding is in process.  Alternatively, an ISO Class 8 or better negative pressure room could be used.  An ISO Class 7 negative pressure room would be necessary if it leads directly into the HD ISO 7 negative pressure buffer room. 
     
  4. Does the chapter apply if the HD is dissolved in a liquid dosage form and does not become an aerosol or gas?
    HDs that do not require any further manipulation, other than counting or repackaging of final dosage forms, may be prepared for dispensing without any further requirements for containment unless required by the manufacturer or if visual indicators of HD exposure hazards are present (e.g., HD dust or leakage).  Consideration must be given to the aerolization of HDs in liquid formulations.
     
  5. If the HD is a liquid dosage form, may it be compounded in a positive pressure non-HD cleanroom?
    No, HD CSPs must be filtered in a BSC or CACI located in an ISO 7 room with negative pressure of 0.01 to 0.03 inches of water and 30 ACPH.
     
  6. What kind of materials may be used for the cabinets and counters in the nonsterile compounding room?
    The chapter states that cabinets in the nonsterile compounding area must be smooth, impervious, free from cracks and crevices, and non-shedding but does not limit or define the specific materials that may be used.

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Hazard Communication Program


 
  1. Do personnel of reproductive capability include both male and females?
    Yes, the chapter applies to anyone capable of reproduction.

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Receiving


 
  1. Are suppliers required to ship HDs in impervious plastic?
    No, the chapter recommends that suppliers ship HDs in impervious plastic to segregate them from other drugs and allow for safety in the receiving and internal transfer process.
     
  2. Does the HD return waiting area have to be separate from the regular HD storage area?
    No, a separate area is not required.  HDs waiting to be returned to the supplier must be segregated in a designated negative pressure area. The regular HD storage area may be designated for this purpose.
     
  3. What container materials are considered impervious?
    The type of impervious packaging will vary with the situation and type of HD.  Impervious packaging may be “soft” or “firm”. HDs must be transported in containers that minimize the risk of breakage or leakage.
     
  4. What is the tiered approach for receiving HDs?
    The tiers will be defined by the entity’s SOPs based on considerations such as the facility design and types of HDs being handled.

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Labeling, Packaging, Transport And Disposal


 
  1. What must be on the label for HDs?
    HDs identified by the entity as requiring special HD handling precautions must be clearly labeled at all times during their transport.  Labeling must be compliant with the appropriate USP standards for compounding including <795> and/or  <797>  and in accordance with applicable federal, state, and local regulations.
     
  2. What kind of packaging containers can be used for packaging HDs?
    The chapter states that packaging containers and materials must be selected to maintain physical integrity, stability, and sterility (if needed) of the HDs during transport. Packaging materials must protect the HD from damage, leakage, contamination, and degradation, while protecting healthcare workers who transport HDs. The entity must have written SOPs to describe appropriate shipping containers and insulating materials, based on information from product specifications, vendors, and mode of transport. Other sources of information may include the chemical or formula and the SDS.  In addition, there are multiple chapters in the USP Compounding Compendium that describes packaging.
     
  3. Can HDs be transported in pneumatic tubes, robots, or patient carts?
    Each facility must conduct an assessment of risk and develop SOPs accordingly. HDs must be transported in containers that minimize the risk of breakage or leakage. Pneumatic tubes must not be used to transport any liquid HDs or any antineoplastic HDs because of the potential for breakage and contamination.
     
  4. Are personnel involved in waste removal and cleaning required to don PPE?
    Yes, personnel must wear appropriate PPE based on their assigned tasks.

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Medical Surveillance


 
  1. What if the employee wants to keep their medical records private from the employer?
    Medical surveillance is recommended but not required by the chapter.  The entity may choose to use a contracted employee health service to perform the medical surveillance while protecting the confidentiality of the employees' personal medical information.
     
  2. What "health variables" should be followed over time for individual workers?
    The chapter recommends an initial baseline assessment (pre-placement) of a worker's health status, medical history and collection of data elements including a medical (including reproductive) history and work history to assess exposure to HDs, physical examination, and laboratory testing.  Methods used to assess exposure history include a review of:
  • Records of HDs handled, with quantities & dosage forms
  • Estimated number of HDs handled per week
  • Estimates of hours spent handling HDs per week and/or per month
  • Performance of a physical assessment and laboratory studies linked to target organs of commonly used HDs such as a baseline complete blood count.
  1. In a medical surveillance program, how does an employer obtain data from the unexposed workers for comparison to the exposed workers?
    The chapter recommends an initial baseline assessment (pre-placement) of a worker's health status, medical history and collection of data elements including a medical (including reproductive) history and work history to assess exposure to HDs, physical examination, and laboratory testing.  Methods used to assess exposure history include a review of:
  • Records of HDs handled, with quantities & dosage forms
  • Estimated number of HDs handled per week
  • Estimates of hours spent handling HDs per week and/or per month
  • Performance of a physical assessment and laboratory studies linked to target organs of commonly used HDs such as a baseline complete blood count.

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