[Submitted electronically via www.regulations.gov]
National Institute for Occupational Safety and Health
NIOSH Docket Office
1090 Tusculum Avenue
MS-C-34
Cincinnati, OH 45226-1998
RE: Docket CDC–2018—0004, Docket Number NIOSH– 233—B for “NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings: Proposed Additions to the NIOSH Hazardous Drug List 2018; Request for Comment”.
ASHP is pleased to submit comments regarding the proposed additions to the NIOSH Hazardous Drug List 2018. ASHP represents pharmacists who serve as patient care providers in acute and ambulatory settings. The organization’s 45,000 members include pharmacists, student pharmacists, and pharmacy technicians. For more than 75 years, ASHP has been at the forefront of efforts to improve medication use and enhance patient safety. ASHP has a long history of supporting the safe handling of hazardous drugs (HDs) that may pose an acute or long-term occupational hazard to healthcare workers.
General Comments
The table and group format currently used by the NIOSH Hazardous Drug (HD) List gives the impression of risk stratification. The draft of USP Chapter <800> further supports this impression by requiring that all sections of the chapter be met for NIOSH Group 1 antineoplastic drugs, but allowing organizations to perform an assessment of risk when determining the application of Chapter <800> to Group 2 and Group 3 drugs. Some Group 1 HDs, specifically hormonal agents used to treat cancer, have similar adverse reproductive affects as HDs listed in Group 3 without the other hazardous characteristics of Group 1 HDs (carcinogenicity, organ toxicity, or genotoxicity). These drugs are not directly cytotoxic in their mechanism of action and many have non-antineoplastic AHFS classes assigned in addition to the 10:00 Antineoplastic Agents class.
ASHP is aware of concerns from its members and others about the unintended consequences on risk stratification interpretation within their practice settings that has resulted from a lack of clear understanding about the NIOSH grouping rationale and intent. Most importantly is confusion about the clear intent of Group 1 since application of USP General Chapter <800> leaves little, if any, room in true assessment of risk at the individual practice setting level. As originally conceived several decades ago, the class 10:00 Antineoplastic Agents was used as a surrogate indicator of a certain level of risk (e.g., cytotoxic/genotoxic). However, with the development of more targeted cancer therapies, including personalized therapies, as well as new mechanisms of action, the designation of a drug as an antineoplastic agent simply means that it is used to treat cancers. What it does not mean is that it carries de facto risk simply based on its use. Therefore, ASHP recommends that NIOSH engage stakeholders in developing more clearly defined risk stratifications for antineoplastic and other agents to address the confusion that now exists in practice, particularly as it applies to risk interpretation and associated mitigation strategies. Addressing the confusion and unintended consequences with NIOSH’s current Grouping model is particularly important as Chapter <800> begins to be enforced.
Hormonal Agents as Group 1 Hazardous Drugs
For the reasons noted above under General Comments, ASHP strongly recommends that hormonal HDs in Group 1 that are exclusively reproductive risks be reassigned to Group 3. We also recommend hormonal HDs in Group 1 that have toxicities other than reproductive risks be reassigned to Group 2.
Examples of hormonal HDs in Group 1 include those that have the following AHFS class assignments in addition to their classification in the 10:00 antineoplastic class:
- 68:16: Estrogens (68:16.04), Antiestrogens (68:16.08), and Estrogen Agonist-Antagonists (68:16.12)
- 68:18: Gonadotropins (68:18.040) and Antigonadotropins (68:18.08)
- 68:32: Progestins
Monoclonal Antibodies as Group 1 Hazardous Drugs
Group 1 of the NIOSH Hazardous Drug List contains AHFS class 10:00 (antineoplastic) agents. Not all Group 1 HDs pose the same level of occupational risk or toxicity; however, the inclusion of all antineoplastic agents in Group 1 regardless of cytotoxicity or mechanism of action implies the same level of risk. Similar to the hormonal agents above, monoclonal antibodies do not have a directly cytotoxic mechanism of action as do conventional antineoplastic agents (e.g. anthracyclines, alkylating agents, antimetabolites). Some monoclonal antibodies present the same toxicities as Group 2 and Group 3 HDs but are categorized in Group 1 simply because of their therapeutic use to treat cancer.
ASHP recommends that monoclonal antibodies that are not directly cytotoxic or conjugated with a cytotoxic agent be moved out of Group 1 to either Group 2 or Group 3 depending on toxicity. This recommendation applies to monoclonal antibodies already on the NIOSH Hazardous Drug List as well as proposed additions to the 2018 List (bevacizumab, blinatumomab, and trastuzumab).
Small-molecule Kinase Inhibitors as Group 1 Hazardous Drugs
Group 1 of the NIOSH Hazardous Drug list also includes small-molecule kinase inhibitors. However, like monoclonal antibodies, these drugs act through a targeted mechanism of action and are not directly cytotoxic. Instead, their principal hazardous risk is reproductive/teratogenic risk. Additionally, other kinase inhibitors have been evaluated by NIOSH and kept off of the Hazardous Drug list (ibrutinib and palbociclib among others). These are members of the 10:00 Antineoplastic Agents class, but have not met the NIOSH definition of hazardous drugs. This is evidence that the AHFS class, alone, does not dictate placement in a specific group.
Therefore, ASHP recommends moving these agents out of Group 1 so that there is an opportunity for allowing organizations to perform an assessment of risk when determining the application of USP Chapter <800>.
Proposed Additions to the 2018 Hazardous Drug List
ASHP agrees with the proposed additions to the NIOSH Hazardous Drug List 2018 with the exceptions below. ASHP asks NIOSH to reconsider the following proposed additions based on the corresponding rationale:
| Generic Drug Name | Proposed Addition | ASHP Recommendation | Rationale |
| Darbepoetin alfa | Table 2 | Exclude |
|
| Interferon beta-1b | Table |
Exclude or Table 3 |
|
ASHP appreciates this opportunity to provide NIOSH with feedback on the proposed additions to the NIOSH Hazardous Drug List 2018. We look forward to continuing to work with NIOSH to protect health and safety. Please contact me if you have any questions on ASHP’s comments. I can be reached by telephone at 301-664-8617 or by email at mganio@ashp.org.
Sincerely,
Michael Ganio, Pharm.D., M.S., FASHP
Director, Pharmacy Practice and Quality
Center on Medication Safety and Quality
ASHP
4500 East West Highway, Suite 900
Bethesda, Maryland 20814
Phone: 301-664-8617