July 30, 2020

[Submitted electronically via www.regulations.gov] National Institute for Occupational Safety and Health NIOSH Docket Office Robert A. Taft Laboratories 1090 Tusculum Avenue MS-C-34 Cincinnati, OH 45226-1998

RE: Docket CDC-2020-0046, Docket Number NIOSH-233-C for “NIOSH List of Hazardous Drugs in Healthcare Settings, 2020; Procedures; and Risk Management Information”.

ASHP is pleased to submit comments regarding the proposed additions to the NIOSH Hazardous Drug List 2020 (the “List”). ASHP represents pharmacists who serve as patient care providers in acute and ambulatory settings. The organization’s 55,000 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

ASHP fully supports the elimination of the AHFS therapeutic classification as a method of categorizing drugs into the List’s tables. An AHFS 10:00 Antineoplastic Agent classification indicates the drug is used to treat cancers, regardless of mechanism of action or toxicity. By removing the AHFS classification from NIOSH categorization, the List is more transparent about the types of risk represented by drugs in each table.

Definition of Hazardous Drugs

ASHP is disappointed to see the scope of the List limited to drugs approved by FDA’s Center for Drug Evaluation and Research (CDER) and the resultant removal of drugs like Bacillus Calmette Guerin (BCG). Therapies approved through a biologics license application (BLA) are handled, prepared, and administered in the same settings as drugs approved through an abbreviated new drug application (ANDA) or new drug application (NDA). On March 23, 2020, several drugs transitioned from approval under section 505 to section 351 of the Food Drug & Cosmetics Act, making them ineligible for the List under the proposed criteria.1 Future transitions could continue making drugs ineligible for inclusion in the List. Occupational risks exist regardless of approval pathway, and a hazard assessment should be made for any drug handled in healthcare settings. ASHP strongly recommends that all drugs, regardless of approval pathway, be eligible for hazard assessment and inclusion in the List.

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1 List of Approved NDAs for Biological Products That Were Deemed to be BLAs on March 23, 2020. https://www.fda.gov/media/135838/download

ASHP Comments to NIOSH re: Hazardous Drug List 2020 July 30, 2020 Page 2

ASHP is also disappointed to see the longstanding definition of a hazardous drug modified through the additional criteria: “unless the drug also exhibits a molecular property that may limit the potential for adverse health effects in healthcare workers from exposure to the drug.” Criteria for the List have been based on an assessment of the hazards of the drug, itself, not physical properties of the molecule. Occupational exposure may occur through several mechanisms, including absorption through the skin, inhalation, or accidental injection through contaminated food or hand-mouth contact.2 Molecular properties that might limit absorption through one route of exposure, such as dermal, may not preclude absorption through another route, such as accidental injection or inhalation. Institutions handling these agents can perform their own assessment of occupational exposure risk for drugs based on packaging, dosage form, manipulations, and other factors. NIOSH should continue to identify the hazard risk for each drug and let institutions assess the level of exposure risk. ASHP strongly recommends NIOSH remove this criteria when considering drugs for inclusion in the List.

Categorization into Table 1 or Table 2

ASHP supports the categorization into tables based on IARC and NTP classification. We express concern over the use of manufacturer’s special handling information (MSHI) as a criteria for categorization. While many hazardous drugs do contain MSHI in the product labeling, there is no requirement to include this information in prescription drug labeling3. Several drugs appear in the proposed Table 1 because of IARC or NTP classification yet they do not include MSHI. This exposes a gap in the criteria for new products that have not yet been evaluated by IARC nor the NTP and do not contain MSHI. ASHP is concerned the use of this criteria will be a disincentive for manufacturers to include safe handling information in product labeling for hazardous drugs in the future.

As an alternative, or perhaps as additional criteria, ASHP proposes consideration of a drug’s mechanism of action. If a new drug is not classified by IARC nor the NTP and does not include MSHI but the mechanism of action is the same or very similar to a drug already in Table 1, the new drug should be included in Table 1 until evidence exists to demonstrate it is not carcinogenic.

List Contents

Based on the categorization recommendation above, ASHP asks that eribulin and carfilzomib be moved from Table 2 to Table 1. Neither drug appears in the IARC and NTP lists, and MSHI do not appear in the product labeling for either drug. Eribulin suppresses microtubule growth through a mechanism similar to vinblastine, paclitaxel, and ixabepilone; all three of which appear in Table 1.4 Carfilzomib is a proteasome inhibitor similar to bortezomib which appears in Table 1. While carfilzomib’s pharmacology varies slightly in that it is an irreversible inhibitor that is more selective for the active binding site than bortezomib, ASHP believes the mechanisms are similar enough to warrant similar categorization.5

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2 Power LA, Coyne JW. ASHP Guidelines on Handling Hazardous Drugs. Am J Health Syst Pharm. 2018 Dec 15;75(24): 1996-2031. https://doi.org/10.2146/ajhp180564 3 21 CFR Parts 201, 314, and 601 Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products. 4 McBride A, Butler SK. Eribulin mesylate: A novel halichondrin B analogue for the treatment of metastatic breast cancer. Am J Health Syst Pharm. 2012 May 1;69(9):745-755. https://doi.org/10.2146/ajhp110237 5 McBride A, Klaus JO, Stockerl-Goldstein K. Carfilzomib: A second-generation proteasome inhibitor for the treatment of multiple myeloma. Am J Health Syst Pharm. 2015 March 1;75(5):353-360. https://doi.org/10.2146/ajhp130281

ASHP Comments to NIOSH re: Hazardous Drug List 2020 July 30, 2020 Page 3

ASHP appreciates this opportunity to provide NIOSH with feedback on the proposed changes to the NIOSH List of Hazardous Drugs in Healthcare Settings. 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 [email protected].

Sincerely,

Michael Ganio, Pharm.D., M.S., BCPS, FASHP Senior Director, Pharmacy Practice and Quality Center on Medication Safety and Quality ASHP 4500 East-West Highway, Suite 900 Bethesda, Maryland 20814