Pharmacy Purchasing & Products: What feedback has NIOSH received since publication of the last iteration of the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings that has been instructive to future updates?

Thomas H. Connor, PhD: Stakeholders have questions related to the process of how we determine what constitutes a hazardous drug (HD). In 2017, the director of NIOSH convened a committee to develop a detailed policy and procedures (P&P) document that delineates how drugs are reviewed for inclusion on the HD list and how final determinations are made. A draft of the P&P was recently published in the Federal Register (see FIGURE on page S6 for a flow chart of this process). It has undergone peer review; when complete, the final approved document will be available on the NIOSH Hazardous Drug Topic page (www.cdc.gov/niosh/topics/hazdrug/).

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Because drug companies are striving to introduce drugs to the market quickly, post-marketing adverse effects must be considered. A record number of medications are being reviewed and approved by the FDA; in fact, NIOSH reviewed approximately 400 new drugs or drugs with new warnings for inclusion in the 2020 HD list update. Once a drug is taken by a large number of patients, adverse effects are likely to occur at a higher rate than is typically seen in clinical trials. Therefore, it is critical that NIOSH consider these adverse events when the NIOSH HD list is updated every 2 years.

The comment period on the proposed 2018 additions closed in mid-April. We are currently reviewing the comments; a draft will then undergo NIOSH and CDC clearance, with the 2018 HD list due to publish in September.

PP&P: What drugs are being considered for addition to or deletion from the 2018 NIOSH HD list?

Connor: No drugs were deleted from the 2018 HD list; the drugs that are proposed for addition to the list can be found in the Federal Register at: www.cdc.gov/niosh/docket/review/docket233b/pdfs/2018-02957.pdf (see TABLE). Given that antineoplastic medications are being approved in high numbers, these drugs account for many of the additions. As the population ages, the incidence of cancer and other chronic diseases increases concurrently, spurring development of medications to treat these conditions.

It is important to note that a significant number of these antineoplastic medications are oral treatments. Consider aromatase inhibitors, for example. Patients take these medications at home over the course of many years. It is important to recognize that the proliferation of HDs in people’s homes increases the risk of accidental poisoning.

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PP&P: Does a drug’s route of administration affect its inclusion on the NIOSH HD list?

Connor: NIOSH does not consider the route of administration in assessing the potential occupational hazard risk of a drug; each drug is evaluated solely on the NIOSH criteria for an HD. The risk is determined by the formulation, how it is used, how often it is used, etc. For example, if a subcutaneous drug requires manipulations similar to an IV drug (eg, reconstitution, drawing up into a syringe, injecting), the safe handling recommendations would be quite similar as well. With liquid or powder medications that must be reconstituted, a CSTD should be used during preparation and administration; this applies to injectable HDs. The risk associated with a pre-filled syringe is somewhat reduced as less manipulation is required. Pre-filled syringes are becoming more prevalent due to the increased convenience they provide, which can lower the risk of exposure as well.

PP&P: Can you provide some recommendations for HD handling practices?

Connor: Organizations should establish the following procedures for proper HD management:

• Identify all HDs used in the facility by comparing the formulary with the NIOSH list. No facility is going to use all of the HDs on the NIOSH list, so this will limit the number of HDs that require an assessment of risk. As new HDs are added to formulary, they should also be assessed.
• Appoint an individual to oversee HD issues for the facility. This role is typically assigned to a pharmacist, although this is not a requirement.
• In addition to proper HD handling methods, staff training should cover why the HD protection is necessary.
• Provide training to all job titles that may come in contact with HDs.
• Utilize engineering controls and PPE that is compliant with USP <800>.

It is critical to understand the nature of the drugs on the NIOSH HD list. Some stakeholders see the drugs in Table 2 of the NIOSH HD list (non-antineoplastic drugs, including those with manufacturer’s safe-handling guidance) as less hazardous than those in Table 1 of the NIOSH HD list (antineoplastic drugs, including those with manufacturer’s safe-handling guidance). While most of the drugs in Table 1 of the NIOSH HD list are cytotoxic, many of the drugs in Table 2 of the NIOSH HD list are known or suspected human carcinogens and teratogens or have other serious toxicities. Therefore, drugs in both Tables 1 and 2 of the NIOSH HD list should be handled with identical precautions. If a male or female worker is at reproductive risk, all drugs in Tables 1 (antineoplastic drugs, including those with manufacturer’s safe-handling guidance) and 3 (non-antineoplastic drugs that primarily have adverse reproductive effects) of the NIOSH HD list, and some in Table 2 (non-antineoplastic drugs, including those with manufacturer’s safe-handling guidance) of the NIOSH HD list, should be handled the same way (drugs in Table 2 that pose a reproductive hazard, in addition to meeting one or more of the other NIOSH criteria, are identified as such).

In addition, consider performing an assessment of risk when multiple forms of a single HD are used in the facility. For example, an intact, coated tablet is low risk, but if that same tablet is crushed and placed in food for a certain population (eg, pediatrics), the manipulation creates increased risk. Administered intravenously, the same drug could require reconstitution and transfer to an IV bag. Thus, one drug can have three levels of risk, all requiring different levels of protection.

PP&P: Given this new generation of more targeted HDs, how can pharmacy reinforce proper PPE use?

Connor: Because newer antineoplastic drugs are more targeted, there is a misconception among some health care workers that these HDs are less toxic than older cancer drugs. This is simply not true. Surveys conducted by NIOSH and other organizations indicate that PPE is not always used as required, even though these newer drugs have significant side effects, especially those involving reproductive toxicities.

Consider tyrosine kinase inhibitors (TKIs) as an example. Many TKIs are being approved or are in use and all of these drugs have serious reproductive effects. In fact, I was one of the authors of an article published last year that detailed the serious possible side effects of these drugs.1 Because TKIs target some of the same pathways that are present in the developing fetus, it is critical that pregnant women limit exposure to these drugs. Some TKIs have other side effects as well; however, the reproductive effects are among the most significant.

To ensure safety, all HDs require use of proper PPE when handled by health care workers. Providing effective education to staff is the best approach to increase PPE use. USP is in the process of developing education and outreach for health care workers about PPE use and safe HD handling, which will be available next year (www.usp.org/healthcare-quality-safety). In fact, NIOSH works quite closely with USP regarding HD topics; NIOSH provided two subject matter experts to the USP <800> Expert Panel, and USP cites the NIOSH list of HDs.

PP&P: What improvements have you observed over the past decade in terms of staff safety with HD handling?

Connor: Although HD handling practice is imperfect, significant strides have been made to ensure safety, including the following:

• Increased awareness of the importance of proper HD handling
• Availability of multiple CSTDs
• IV drug preparation in the cleanroom is now the norm, rather than the exception
• Availability of a variety of chemotherapy-approved gloves
• Increased utilization of surface wipe sampling to identify contamination concerns

These improvements are likely due to an increased focus on HD education and training. Ongoing training and education are necessary to maintain these gains moving forward.

Reference

1. Cass Y, Connor TH, Tabachnik A. Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting. J Oncol Pharm Practice. 2017;23(5):350–378.

Thomas H. Connor, PhD, received his BS and MS in microbiology from the University of Rhode Island, and his PhD in environmental toxicology from The University of Texas Medical Branch, Galveston. He joined NIOSH in 2001 as a research biologist focusing on occupational exposure to hazardous drugs. Tom was the lead author on the NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs, along with other related NIOSH documents. He recently retired from NIOSH and now serves as a consultant to NIOSH on HD-related topics.