Updates to USP 800 Regulations: What Healthcare Professionals Need to Know

Overview of USP 800 Guidelines

The USP 800 guidelines include standards used for the safe handling of hazardous drugs for all healthcare personnel who receive, prepare, administer, transport, or come in contact with hazardous materials in a healthcare setting. This acts to minimize the risk of contamination to patients and exposure to hazardous materials to healthcare personnel and the environment. 

A drug is deemed hazardous through the National Institute for Occupational Safety and Health’s (NIOSH) definition. It must exhibit one or more of the following in humans or animals; carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, or structure and toxicity profiles of new drugs that mimic existing hazardous drugs. It is important to comply with these regulations to keep the patient, healthcare personnel, and environment free of any hazardous material. ²

General Chapter 800 was published in February 2016 and further revised in 2019. This chapter is considered informational at the time being but will be compendial applicable when general chapter 797 is finalized on November 1, 2023.³ The regulations provide a wide range of content including responsibilities of hazardous drug compounding, engineering and facility controls, procedures for deactivating, decontamination and cleaning, spill control, cleanroom preparation, personal protective equipment (PPE) information, and documentation.²

Key Changes and Updates to USP 800 Regulations 

Some of the NIOSH-classified hazardous drugs include Anastrazole, Cisplatin, Carbamazepine, Leuprolide, Divalproex, Methotrexate, Progesterone, Finasteride, Warfarin, Tamoxifen, and many more.4 This list must be reviewed every 12 months based on an assessment of risk. This assessment includes the type of hazardous drug, its dosage form, risk of exposure, packaging, and manipulation requirements. 

The handling and disposal requirements of hazardous drugs are two main pieces stated in the USP general chapter 800 guidelines. Hazardous drugs (HDs) must be handled under safe conditions for the patient receiving the drug, and the workers handling the drug, and also environmentally safe. The HD handling areas must be designated using signs to prominently display the entrance to hazardous territory and only authorized personnel are allowed. These areas must be away from breakrooms, refreshment areas, or any area that patients or visitors can enter to reduce exposure risk. There must be assigned spaces for receipt and unpacking of the HDs, storage of HDs, nonsterile compounding, and sterile compounding with negative pressure surrounding the areas that have uninterrupted power sources for ventilation in the event of power loss. 

The proper disposal of HD and their trace contaminants is very important when working with hazardous drugs. All PPE worn and equipment used when handling HDs must be considered contaminated and placed in appropriate waste containers, which are further disposed of per local, state, and federal regulations. Chemotherapy equipment used/worn during compounding must be removed and discarded immediately approved for trace contaminated waste inside of the primary engineering control (PEC) areas or contained in a bag for discarded outside the PEC. No equipment or PPE can ever be re-used once used once for HDs. 

The four steps of cleaning the area after handling HDs include deactivation, decontamination, cleaning, and disinfection. 1. Deactivation renders the compound inactive using Environmental Protection Agency (EPA)-registered oxidizers like peroxide formulations or sodium hypochlorite. 2. Decontamination removes HD residue using include alcohol, water, peroxide, or sodium hypochlorite. 3. Cleaning removes organic and inorganic material using a normal germicidal agent. 4. Disinfection destroys microorganisms using an EPA-registered disinfectant or sterile alcohol. Once the area is cleaned and the HDs are disposed of, the area can be set up to compound another HD. 

Access to HD handling areas is authorized to specific personnel. HDs must be unpacked in an area that is neutral or negative pressure relative to surrounding areas. Once unpacked, they must be stored in a way that spillage/breakage is prevented if the HD falls. Antineoplastic hazardous drugs requiring manipulation other than counting or repacking and any active pharmaceutical ingredient HDs must be stored away from non-HDs to prevent contamination. Instead, they have to be in an area that is externally ventilated with negative pressure and at least 12 air changes per hour. Non-antineoplastic HDs with reproductive risk only and final dosage forms of antineoplastic HDs can be stored with other non-HDs if permitted. Sterile and nonsterile HDs can be stored together but the ones used for nonsterile compounding should not be in sterile areas to minimize contact with the sterile compounding area. Refrigerated antineoplastic HDs must be stored in a refrigerator dedicated to them with negative pressure and at least 12 air changes per hour. If this happens to be in a negative pressure buffer room, an exhaust should be added adjacent to the compressor and behind the refrigerator. HDs that need to be transported from their storage area must be labeled, stored, and handled by federal, state, and local regulations. They must be in containers that minimize breakage or leakage risk with labels and accessory labels including storage instructions and HD category information following the specific carrier’s new and revised compounding standards. 

Engineering controls are required to prevent contamination during compounding. There are three categories of controls including primary, secondary, and supplementary. Containment primary engineering controls (C-PECs) are ventilated devices that minimize worker and environmental exposure while directly handling HDs. Containment secondary engineering controls (C-SECs) is the room that contains C-PECs. Supplemental controls are any adjunct used in a specific environment for extra protection. All HDs whether they are sterile preparations or not must be compounded and handled in a C-PEC that is located in a C-SEC. The C-SEC must be externally vented, have appropriate air change per hour, be physically separated from other preparation areas, and have negative pressure between 0.01 and 0.03. When compounding nonsterile and sterile preparations, USP 795/797 must be followed additionally based on which type of compounding is being done. 

The correct personal protective equipment must be worn at all times during HD receipt, storage, transport, compounding, administration, cleaning, spill control, and waste disposal. This provides worker protection to reduce HD exposure and contamination. Gowns, head/hair/shoe covers, and two pairs of chemotherapy gloves are required for compounding sterile and nonsterile HDs. Chemotherapy gloves must meet American Society for Testing and Materials (ASTM) standard D6978, be changed every 30 minutes or when contaminated/torn, and be powder-free. Gowns must be disposable and able to resist permeability to HDs when worn to administer injectable antineoplastics. Two pairs of chemo gloves are required when administering antineoplastic HDs. Aside from these requirements, an entity’s standard operation procedures must describe what PPE is to be worn based on their occupational safety plan and risk assessment. PPE must be disposed of in appropriate waste containers when finished and never re-used. 

All personnel handling the HDs must be trained based on what they will be doing with them. At every site, the minimum training includes an overview of the entity’s list of HDs and their risks, a review of the standard operating procedures related to HDs, proper use of PPE, proper use of equipment and devices, response to HD exposure (known or suspected), spill management, and proper disposal methods. This training must be done before the employee handles the HDs and the effectiveness of the training is shown for each employee. Once the employee begins working with HDs, they are reassessed every 12 months and trained before the introduction of a new HD, new equipment, or significant changes at their workplace. Once an employee is trained and competency is assessed, documentation occurs and is kept the whole time that individual is employed at that site. 

Personnel that may be required to help with spill management must receive extra training in spill management. Standard requirements include that spills must be contained and cleaned immediately by qualified personnel, wearing appropriate PPE. Spill area must be restricted using signs and materials used for cleaning must be disposed of as hazardous waste. Once cleaned, the circumstances and management of the spill must be documented while personnel who were exposed are evaluated immediately. For a smooth transition in case of a spill, standard operating procedures (SOPs) are required to be developed to prevent spills and direct the cleanup in case of emergency. The SOPs must have information on the size and scope of the spill, talk about required PPE, address the location of spill kits, and state who is responsible for spill management.⁵ Although USP 800 is considered informative right now, it will be turned to a requirement as of November 1, 2023, along with the other updates in USP 797.⁶

Implications for Healthcare Professionals
The roles and responsibilities of healthcare professionals include staying up to date on recent and future changes to USP, developing SOPs for their sites based on the risk of exposure, and educating their employees on the importance and crucial rules of USP. As USP 800 becomes enforceable instead of informational, the NIOSH list of hazardous drugs becomes a vital part of compounding programs at different organizations.⁷

Compliance with USP 800 is critical in assuring the safety of employees, patients, and the environment but this comes with challenges and considerations. There is an abundance of information and training that is needed to reach compliance with the regulations. Challenges of compliance include training all personnel working with hazardous materials and creating compliant SOPs in case of an emergency. Important considerations should be taken when onboarding new employees to map out ample time for them to become fully trained in USP regulations to avoid complications in the future. Healthcare professionals should develop SOPs based on the USP guidelines directly and mimic step-by-step example procedures when writing what to do in case of a spill, leak, exposure, etc. — It is important to incorporate these into existing policies and procedures so not all of the information is new for employees. Some of the new enforceable regulations may already be in place at your organization so a thorough check to make sure there is no overlap can help to avoid confusion with the new rules. 

Healthcare professionals can comply with USP 800 by following their organization's SOP, reviewing the new revisions to the chapters, and staying up-to-date with training procedures. Ensuring all hazardous drug training and competencies are current with documentation will avoid any conflict with inspectors. Facilities should further identify the hazardous drugs they handle, get safety data sheets and store hazardous and non-hazardous drugs to avoid contamination of non-HD medications. Any new hazardous drugs or dosage forms introduced must be reviewed using the NIOSH criteria list. An annual risk assessment of each hazardous drug is required that includes the type of HD, dosage form, risk of exposure, packaging, and manipulation information to maintain compliance.⁸

Conclusion

USP 800 guideline compliance is crucial when working with hazardous drugs for patient, employee, and environmental safety. These guidelines showcase everything from receiving to disposal of hazardous drugs and help ensure safety for anyone manipulating them. They have gone through notable updates and changes over the past few years so it is important to keep up with the modifications as healthcare professionals. As of November 1, 2023, the regulations will be finalized alongside other general chapter standards.