USP 800 risk assessment: Compliance and protection essentials
Hazardous drugs are defined by six criteria, including carcinogenicity, teratogenicity, developmental toxicity, organ toxicity at low doses, genotoxicity, and new drugs that mimic existing hazardous profiles. The hazardous drugs addressed by USP <800> are those that pose risks to individuals handling them, distinguishing them from hazardous materials regulated by the EPA, which primarily concern environmental safety. The three distinct categories of hazardous drugs identified by NIOSH include:
- Antineoplastics – Drugs primarily used in cancer treatment.
- Non-antineoplastics – Drugs that meet the hazardous criteria but are not typically used to treat cancer.
- Reproductive hazards only – Drugs that pose a particular risk to reproductive health.
Exposure to these drugs, even in trace amounts, can lead to serious health effects such as reproductive issues, congenital disabilities, and increased cancer risk. These risks underscore the critical importance of implementing stringent safety measures wherever hazardous drugs are handled, prepared, or administered.
While there is some overlap between these categories, the definitive resource for USP <800> compliance is the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, which was updated in December 2024i.
The NIOSH list of hazardous drugs is now divided into two groups:
Table 1 - Drugs that:
- Have safe handling guidance in the manufacturer’s package insert and/or
- Meet the NIOSH definition of a hazardous drug and one or more of the following:
- Classified by the NTP as “known to be a human carcinogen” orAre classified by IARC as Group 1, “carcinogenic to humans” or Group 2A, “probably carcinogenic to humans
Table 2 – Drugs that:
Meet the NIOSH definition of a hazardous drug
- Do not have manufacturer’s safe handling guidance,
- Are not classified by NTP as “known to be a human carcinogen”
- Are not classified by IARC as Group 1, “carcinogenic to humans” or Group 2A, “probably carcinogenic to humans”
- Some may also have adverse developmental and/or reproductive effects.
The full protections outlined in USP <800> are required for all antineoplastic drugs listed in Table 1 and any hazardous active pharmaceutical ingredient (API). However, USP <800> allows for organizations to conduct an Assessment of Risk (AOR) for other drugs on the NIOSH list to determine if alternate work practices or containment strategies may be used to minimize the risk of hazardous drug exposure.
Understanding USP 800 requirements to determine AOR
The USP 800 Assessment of Risk must, at a minimum, consider the following:
- Type of HD (e.g. refer to updated Table 1 and Table 2)
- Dosage form (e.g. tablet, vial, infusion)
- Risk of exposure (e.g. dermal, inhalation, ingestion)
- Packaging (e.g. unit dose, bulk package)
- Manipulation (e.g. compounding, crushing)
Develop and implement an AOR
Review the updated NIOSH list to identify the hazardous drugs and dosage forms you handle. Track these drugs through their entire lifecycle in the health system to ensure safe handling practices.
- Identify which drugs and dosage forms are handled.
- Trace the drugs from receiving and storage through preparation, dispensing, administration, and disposal.
- Determine where the drugs are handled and by whom.
- Assess who requires training for the safe handling of hazardous drugs.
- Keep thorough documentation of the AoR process to demonstrate compliance during inspections
Optimize engineering and environmental controls
For hazardous drugs that require full containment, organizations must ensure their facilities have appropriate engineering controls, such as:
- Compounding in a certified negative-pressure containment primary engineering control (C-PEC) located within a negative-pressure containment secondary engineering control (C-SEC).
- Establishing segregated compounding areas with HEPA filtration systems to limit contamination.
- Routine environmental monitoring, such as surface wipe testing for hazardous drug residue, helps identify contamination hot spots and validate the efficacy of containment measures.
Train and protect staff
Healthcare personnel are at the greatest risk of hazardous drug exposure. Comprehensive training programs are essential to promote safety. These programs should cover:
- Proper use of PPE, including gloves, gowns, and respirators.
- Techniques for decontamination, cleaning, and disposal of hazardous drugs and associated waste.
- Emergency protocols for accidental exposures or spills.
- Employers should enforce regular competency assessments to confirm staff adherence to procedures.
Some organizations may have based their AOR strategy on the previous three table designations in the NIOSH list, particularly Table 3 drugs with primarily reproductive risks. Take this opportunity to re-assess your approach to AOR, especially the risk of exposure. Limiting protections to those workers during the period of conception and/or pregnancy may be difficult for a variety of reasonsii. Expanding protections for drugs with reproductive risks helps prevent the exposure for all workers, regardless of their reproductive status.
Leverage technology to ensure compliance
Healthcare organizations can utilize digital tools like Simplifi 797® to streamline the implementation of USP 800 standards. These solutions provide evidence-based guidance, inspection readiness checklists, and automated workflows, reducing the burden of manual compliance management.
Conduct periodic internal audits
Internal audits are invaluable for evaluating adherence to USP 800 and identifying areas for improvement. The audit scope should include:
- Review of documentation, including AOR records and environmental monitoring data.
- Observation of compounding practices and PPE utilization.
- Assessment of facility maintenance and equipment validation schedules.
If your organization has already implemented USP <800> practices, review any spill or safety incidents related to HDs in the past year. Consider these questions to further evaluate hazardous drug safety:
- Were all safe handling practices followed?
- Does the assessment of risk need to be updated for that drug?
- Are there new types of manipulation that might increase the risk of exposure?
- Are there new drugs or packaging that might reduce the risk of exposure?
By conducting proactive reviews, healthcare organizations can correct deficiencies before they escalate into compliance violations. Regardless of whether you have implemented USP <800>, the release of the updated NIOSH List presents an opportune time to re-evaluate your organization’s hazardous drug list and assessment of risk. Be sure to document your review and schedule the next review within at least 12 months, as required by USP <800>.
The importance of compliance with USP 800
Compliance with USP 800 is not merely a regulatory requirement, but a vital component of occupational safety and public health. Adherence safeguards the well-being of healthcare personnel and patients, ensuring that hazardous drugs are handled without compromising safety standards. Investing in proper training, infrastructure, and monitoring tools reinforces a culture of safety and reduces the likelihood of harmful exposure.
By staying informed about regulatory updates, performing a holistic risk assessment, and fostering a commitment to continual improvement, healthcare organizations can confidently meet the challenges of USP 800 compliance.
