Like time, regulatory compliance waits for no one. Following official enforcement of USP General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings on December 1, 2019, all institutions handling hazardous drugs (HDs) must meet the standards and will be held liable through federal, state, and accrediting bodies.

With the effective date quickly approaching, it is crucial that institutions facilitate collaboration and engagement among all disciplines at risk for HD exposure. Critical to USP <800> compliance is the development and maintenance of an organization-specific HD list to ensure safe handling throughout the health system. (The history and development of USP <800> is discussed in the SIDEBAR.)

The University of North Carolina (UNC) Health Care System is a not-for-profit, academic medical system whose flagship campus, UNC Medical Center (UNCMC), located in Chapel Hill, comprises six hospitals. The NC Cancer Hospital, serviced by the UNC Lineberger Comprehensive Cancer Center, is one of 49 National Cancer Institute-designated centers in the United States and is the only public comprehensive cancer center in the state of North Carolina.

Within our department, several pharmacy operational areas store, compound, dispense, and transport HDs, although the vast majority of HDs are prepared in the Cancer Hospital Infusion/Inpatient Pharmacy (CHIP). To ensure HD safety throughout the medication-use process, UNCMC is committed to USP <800> compliance. As such, developing an entity-specific HD list is a critical priority. While the methodology for developing the HD list is being utilized across our entire health care system, the HD list described is specific to UNCMC.

Conduct a Compliance Assessment

Protecting our employees and meeting USP <800> requirements were the driving forces behind the pharmacy department’s decision to conduct a baseline USP <800> compliance assessment. This assessment identified areas of noncompliance, including outdated policies and procedures (P&Ps) for the institutional risk assessment review process and the lack of an up-to-date, entity-specific HD list.

To address these areas of noncompliance, an interdepartmental USP <800> work group was established with the mandate of ensuring key stakeholder involvement, identifying risks, and supporting continual compliance efforts through ongoing planning. In addition to pharmacy, the work group included leadership from environmental health and safety (EHS), epidemiology, operational excellence, and nursing.

Assess Existing Institutional P&Ps

The pharmacy department is well positioned to assume ownership of developing and maintaining the institution-specific HD list. All UNCMC pharmacy operational leaders who handle HDs collaborated to address existing gaps in our outdated HD list. The group revised the HD list to incorporate the 2016 NIOSH updates and information from pertinent literature for drugs handled by the facility.

UNCMC risk categories for drug classification were organized into the following two categories:

• HDs: The HD category includes all drugs from Table 1 of the NIOSH list and a subset of drugs from Table 2

• Reproductive Risk: Any Table 2 drug from the NIOSH list that was not defined as hazardous, as well as all Table 3 drugs from the NIOSH list, are categorized in the reproductive risk category

Developing clear processes to assess drug risk ensures that all drugs will be evaluated in a uniform manner moving forward. To determine the classification for the NIOSH Table 2 drugs as either hazardous or reproductive-risk, we developed an internal risk assessment algorithm (see FIGURE 1). Classifying HDs into two categories for the institutional HD list both met the USP <800> requirement and simplified the HD management process across UNCMC’s medication-use system. The simplified process was developed following recommendations made by the institutional multidisciplinary USP <800> working group. This working group determined that redundant P&Ps for HD handling across disciplines would be significantly reduced by developing and incorporating these classifications into the electronic health record (EHR). Integrating the two designated classifications (hazardous or reproductive risk) into the EHR and on printed medication labels provided clarity to pharmacy, nursing, and support staff who frequently handle HDs.

Prior to operationalizing the category changes, proposals were approved by appropriate hospital pharmacy leadership, a clinical informatics group, and the collaborative USP <800> work group. Assignment into either risk category, HD or reproductive-risk, dictates the recommended procedures to follow when handling, preparing, administering, and disposing of each drug listed.

HD Classification and Assessment of Risk

An HD risk assessment and subsequent risk category assignment is routinely performed during the review process for any new drug being considered for formulary addition. FIGURES 1 and 2 outline the approach used by UNCMC to assess the risk of new drugs considered for formulary addition and the associated handling recommendations. The risk assessment requires the following steps:

1. Determine if the drug is considered hazardous, made evident by the presence of one or more of the following criteria in the package insert (NIOSH also uses this criteria in evaluating drugs)1:
• Carcinogenicity
  Carcinogenicity in animal models, the patient population, or both, as reported by the International Agency for Research on Cancer (IARC)
• Genotoxicity
  Including mutagenicity and carcinogenicity in short-term test systems
• Teratogenicity
  Teratogenicity or fertility impairment in animal studies or in treated patients
• Reproductive and Developmental Toxicity
  
• Organ Toxicity at Low Doses
  Defined as daily therapeutic dose of 10 mg per day or 1 mg per kg per day in laboratory animals
• Structure and toxicity profiles of new drugs that mimic existing drugs established as hazardous by the above criteria

1. Any drug meeting one or more of the above criteria should use UNCMC’s Risk Assessment Algorithm (see FIGURE 1) to determine risk category
2. Drugs not meeting the above criteria will not be handled as HDs

The risk classification of each drug on the HD list is reassessed annually by the pharmacy department, and the list is updated each time a new HD is added to formulary.

Implementation, Education, and Staff Training

Ensuring frontline staff is aware of and knowledgeable about institutional HD list changes requires deliberate, frequent communication. At UNCMC, the HD list is stored on an internal shared drive that is accessible to all personnel and embedded within our HD P&P. While the policy area is designated as EHS, the content applies to UNCMC as a whole. Various departments, including pharmacy, are responsible for implementing this policy and reviewing the requirements at least annually.

The pharmacy department is accountable for the list, which is available in the TABLE. Pharmacy oversees the following actions regarding HD list evaluation and changes:

Click here to view a larger version of this Table

1. All drugs being considered for formulary addition are evaluated as a potential HD by the Pharmacy and Therapeutics (P&T) Committee, using the NIOSH list as a guide
2. The P&T committee approves the HD list in its entirety, including any changes
3. The list is maintained by the pharmacy department
4. The pharmacy department coordinates with EHS to ensure availability of Safety Data Sheets (SDSs)
5. The HD list is accessible in the UNCMC P&P
6. The HD list is reviewed every 12 months (at a minimum)

When considering a drug for formulary addition, the P&T committee utilizes a checklist to ensure that the appropriate committees are made aware of changes. All drugs approved for formulary use at UNCMC go through the pharmacy informatics committee to ensure the drug is built appropriately within the EHR medication list. When the P&T committee deems a drug to be a hazardous or reproductive risk, the pharmacy informatics team is responsible for adding a banner that prints at the top of the drug label designating it as such. In addition, administration instructions are configured to auto-populate, instructing the handling employee as to which PPE to don and referring them to the appropriate HD policy.

FIGURES 3 and 4 provide visual examples of the UNCMC drug labels for drugs deemed hazardous and reproductive risk, respectively. Any changes in the hazardous risk status of existing medications are brought through the pharmacy informatics committee for approval and implementation of any necessary changes.

Click here to view a larger version of these Figures

An overview of the HD list, including a review of the risks associated with handling HDs, is included in the training for all new personnel. We evaluate staff knowledge and document competency after the first training session and then annually thereafter for all personnel prior to permitting independent HD handling. All P&P changes are communicated to staff verbally via in-person meetings, through email communications, or by signage posted in the work area.

Conclusion

Pharmacy personnel play a significant role in handling, preparing, distributing, and disposing of hazardous medications throughout the medication-use process. Thus, pharmacy departments have a responsibility for implementing P&Ps that are designed to protect the safety of those handling hazardous medications, as well as the environment.

It is reasonable for pharmacy departments to assume accountability for maintaining the institution-specific HD list in a manner that is compliant with USP <800> standards, and for ensuring that the institution is carefully and conservatively assessing any medications new to the formulary. The creation of a pharmacy operational work group to oversee gap assessment, development of risk categories and a risk assessment, and implementation of a standardized process to review new drugs for hazardous risk is an effective method of identifying and addressing compliance gaps.

Pharmacy departments must take an active role in continually reviewing, educating, and training personnel on their institution’s specific HD list to ensure successful USP <800> compliance, and ultimately, to keep their staff and patients safe.

Reference

1. Centers for Disease Control and Prevention/National Institute of Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. www.cdc.gov/niosh/docs/2016-161/pdfs/2016-161.pdf. Accessed May 2, 2019.

Elissa King, PharmD, MS, BCPS, is the clinical manager of pharmacy for the offsite infusion centers at the University of North Carolina (UNC) Medical Center. She earned her Doctor of Pharmacy Degree from the University of Maryland and her Master of Science degree with an emphasis in health-system pharmacy administration from the UNC Eshelman School of Pharmacy while completing her 2-year health system pharmacy administration residency at UNC Hospitals. Elissa is a board-certified pharmacotherapy specialist. She maintains active professional involvement as a new practitioner mentor for the Carolina Association of Pharmacy Students and within the American Society of Health-System Pharmacists.

Samuel M. Eberwein, PharmD, MS, BCPS, is the clinical manager of pharmacy for the sterile products area, perioperative services, and special formulations at the University of North Carolina (UNC) Medical Center. He earned his Doctor of Pharmacy degree from Campbell University and his Master of Science degree with an emphasis in Health-System Pharmacy Administration from the UNC Eshelman School of Pharmacy while completing his 2-year Health System Pharmacy Administration residency at UNC Hospitals. Sam is a board-certified pharmacotherapy specialist. He maintains active professional involvement in ASHP.

SIDEBAR

The History of NIOSH and the Development of USP <800>