In 2019, new guidelines on handling hazardous drugs (HDs) were proposed by the U.S. Pharmacopeial Convention (USP), with an impact on care settings ranging from hospitals to ambulatory surgery centers, physician offices, specialty clinics, cancer centers and post-acute care facilities. The United States Pharmacopeia General Chapter <800> standards focus on controlling occupational exposure to hazardous drugs while also protecting patients.
This convention was prepared to implement USP General Chapter <800> on December 1, 2019, which would have been an enforceable standard for managing sterile and non-sterile hazardous pharmaceuticals; however, a last-minute appeal just prior to the COVID-19 pandemic changed USP <800> from enforceable to "informational" and not applicable compendially. Despite the current non-enforceable status by USP, the Occupational Safety and Health Administration (OSHA) and state pharmacy boards provide ample penalties for safety violations and a clear incentive for adopting best practices.
The USP <797> Pharmaceutical Compounding of Sterile Preparations and USP <795> Pharmaceutical Compounding of Nonsterile preparations were inextricably linked to USP <800> Hazardous Drug Handling in Healthcare Settings. USP General Chapter <800> describes requirements including:
- Responsibilities of personnel handling hazardous drugs
- Facility and engineering controls
- Procedures for deactivating, decontaminating and cleaning
- Spill control
One of the primary issues raised by key stakeholders that prompted the appeal was related to beyond-use-date requirements. On August 31, 2021, USP published a briefing to improve clarity and respond to stakeholder input. The Compounding Expert Committee proposes to revise USP <795> with the following major edits:
- Expand guidance for assigning beyond-use dates (BUDs) for compounded nonsterile preparations (CNSPs) in the absence of stability information
- Elaborate on the role of water activity in determining BUD limits for preparations
- Add a table of commonly compounded dosage forms and their respective values to aid compounders in determining BUD limits for CNSPs
- Clarify the requirements for identifying the need for a recall and related procedures. An additional briefing was issued regarding USP <797> Pharmaceutical Compounding - Sterile Preparations
According to USP, beyond-use dates help decrease the risks by identifying when a compounded pharmaceutical must be used before it is at risk for physical or chemical degradation, microbial contamination and proliferation and impact on the integrity of the container closure system. Reducing the confusion related to BUDs is likely to improve safety for healthcare professionals that are often not directly involved in the compounding process within the patient care environment.
This proposal, published in August 2021, is based on the version of the chapter that was official as of May 1, 2020. The Compounding Expert Committee proposes to revise this chapter to improve clarity and to respond to stakeholder input. Major edits to the chapter include:
- Reorganize the chapter to group similar topics and clarify requirements. Include section and subsection numbers and place procedural information in boxes
- Expand guidance for assigning BUDs for compounded sterile preparations (CSPs)
- Rename CSP microbial risk levels and update terminology. Category 1 and 2 CSPs are distinguished primarily by the facility in which they are made and the length of time within which they must be used
- Category 1 CSPs have shorter BUDs and may be prepared in an unclassified segregated compounding area; Category 2 CSPs have longer BUDs and must be prepared in a cleanroom suite. Additionally, Category 3 CSPs are those that may be assigned longer BUDs than the limits for Category 1 or Category 2 CSPs, up to 180 days, if additional requirements are met
- Add a maximum batch size of 250 final yield units for all CSPs requiring sterility testing
- Add guidance on assigning BUDs to compounded multiple-dose containers, including information on assigning BUDs for non-preserved ophthalmic CSPs
- Add guidance on the use and storage of entered or punctured conventionally manufactured products
- Add information on notification and recall of CSPs with out-of-specification results
- Clarify requirements for compounding allergenic extract prescription sets
- Add requirements for maintaining master formulation and compounding records
- Provide guidance on the use of isolators
- Remove specific information related to the handling of hazardous drugs and add cross-references to Hazardous Drugs - Handling in Healthcare Settings <800>
- Remove specific information related to radiopharmaceuticals as CSPs and add cross-references to Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging <825>
The National Institute for Occupational Safety and Health (NIOSH) issued the "Draft of the NIOSH List of HDs in Healthcare Settings, 2020" which as of December 2021, remains in a post-comment period until finalized.1 Although the draft does not represent an enforceable agency determination or policy, it's likely to increase compliance complexity for healthcare professionals. The proposed NIOSH list is limited to drugs approved and evaluated by the Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and would no longer include products approved by the Center for Biologics Evaluation and Research (CBER).2
The Occupational Safety and Health Administration (OSHA) is responsible for enforcing the Hazard Communication Standard, which includes HDs and any other drug substance that pose a health hazard (except those in a solid, final form for direct administration to the patient). OSHA introduces the importance of implementing best practices on its Safety and Health Topics webpage that although some HDs have specific OSHA standards, "many of the requirements arise out of professional documents and good management practices."3
About USP General Chapter <800>
USP <800> incorporates the National Institute for Occupational Safety and Health (NIOSH) definition of hazardous drugs — cancer therapy drugs and some antivirals, hormone agents and bioengineered drugs.4 Each healthcare entity must maintain a list of all hazardous drugs used in their facilities, along with a risk assessment by drug type, dosage form, exposure potential and packaging.
By design, USP <800> compliance affects health system operations, cancer care centers, surgery centers and other practices that handle hazardous drugs, from the loading dock all the way through clinician touchpoints. Requirements specify responsibilities of personnel handling hazardous drugs; facility and engineering protocols; procedures for deactivating, decontaminating and cleaning all areas where hazardous drugs are handled; availability of spill kits; and compliance documentation.5
When USP <800> becomes enacted, noncompliance will carry potential financial penalties. Due to the complexity of meeting enacted standards, stakeholders should take USP <800> seriously and start to create a compliance strategy.
Compliance best practices
Many leading centers are seeking out supply chain experts like McKesson Medical-Surgical for support while preparing for USP <800> to "go live."
We actively consult with community oncology and affected non-acute clinics to help identify gaps in their policies and procedures. An Excel-based readiness assessment tool helps to identify which aspects of USP <800> are mandatory or discretionary. Using the tool, "providers can see where they are today and where they need to be," explained Julie Cothren, pharmacist and clinical specialist with McKesson's Provider Advisory Services team.
We also offer USP <800> compliance support in the following areas:
- Engineering and construction assessment. Antineoplastic hazardous drugs that require manipulation must be prepared in a vented biological safety cabinet (BSC) that is located in a negative pressure room with a minimum number of air changes. USP <800> allows for a less restrictive containment-segregated compounding area (CSCA), which includes fixed walls, external ventilation with 12 air changes per hour, and maintains specified negative pressure readings relative to adjacent areas.6 Drugs prepared in the C-SCA must have a 12 hour or less BUD. McKesson pharmacy advisors consult with oncology clinics to flag engineering or construction changes required for USP <800> compliance. "Many practices have a hood, but it's not vented outside," Ms. Cothren pointed out. Alternatively, "They may have an externally vented hood, but it's not in a negative pressure room, and the room doesn't support the proper number of air changes," she said
- Product formulary. Controlling occupational exposure to hazardous drugs requires medical-surgical products vetted according to USP <800> standards. Compliant products should include closed system transfer devices; personal protective equipment that meets American Society for Testing and Materials standards; needleless equipment for preparing hazardous drugs; gloves, gowns, hoods and shoe covers; cleaning and decontamination products; and waste disposal systems
- Education. Protecting providers and patients from exposure to hazardous drugs starts with comprehensive education and communication. Our USP <800> educational initiative, now in its third year, keeps customers up to date through an ongoing series of webinars and emails. "Our goal is to break USP <800> compliance down into manageable pieces, so providers aren't overwhelmed," said Ms. Cothren. "We help them work toward readiness one step at a time."
- Training. USP <800> training must address the development and implementation of appropriate procedures; entity compliance with applicable laws, regulations and standards; personnel competency assessment; and evaluation of environmental control in storage and compounding areas. MedTrainer's USP <800> toolkit provides a formal structure for employee training. The toolkit's training modules guide personnel through the identification, assessment and handling of hazardous drugs, as well as creation and maintenance of standard operating procedures
The ultimate goal
USP <800> directs healthcare entities in acute and non-acute environments to create, maintain and enforce standards for preventing accidental hazardous drug exposure. A thorough understanding of the guidelines on handling hazardous drugs, coupled with assessment of compliance gaps and remediation where necessary, can help support healthcare facilities' goal of protecting workers and patients.
1: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Draft NIOSH List of Hazardous Drugs in Healthcare Settings, 2020; Procedures; and Risk Management Information; Extension of Comment Period, Docket No. CDC-2020-0046; NIOSH-233-C, June 19, 2020.
2: Fred Massoomi, PharmD, BCSCP, FASHP, Complying with USP <800>, Pharmacy Purchasing and Products, Vol. 18, No. 12, December 2021.
3: United States Department of Labor, Occupational Safety and Health Administration, Hazardous Drugs, taken from OSHA website, https://www.osha.gov/hazardous-drugs/standards, December 18, 2021.
Be advised that information contained herein is intended to serve as a useful reference for informational purposes only and is not complete clinical information. This information is intended for use only by competent healthcare professionals exercising judgment in providing care. McKesson cannot be held responsible for the continued currency of or for any errors or omissions in the information.
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