[Federal Register Volume 89, Number 10 (Tuesday, January 16, 2024)]
[Notices]
[Pages 2614-2615]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-00693]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Docket Number CDC-2020-0046, NIOSH-233-C]


Request for Public Comment on NIOSH Initial Recommendations To 
Change the Status of Liraglutide and Pertuzumab on the NIOSH List of 
Antineoplastic and Other Hazardous Drugs in Healthcare Settings

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Request for comment.

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SUMMARY: The National Institute for Occupational Safety and Health 
(NIOSH) of the Centers for Disease Control and Prevention (CDC), in the 
Department of Health and Human Services (HHS), requests public comment 
on two draft reevaluations with initial recommendations to change the 
status of two drugs, liraglutide and pertuzumab, on the NIOSH List of 
Antineoplastics and Other Hazardous Drugs in Healthcare Settings 
(List). The reevaluations were developed based on the process described 
in the NIOSH Procedures for Developing the NIOSH List of Hazardous 
Drugs in Healthcare Settings. Based on the reevaluations, the NIOSH 
initial recommendations are to remove liraglutide and pertuzumab from 
the List.

DATES: Electronic or written comments must be received by February 15, 
2024.

ADDRESSES: You may submit comments, identified by CDC-2020-0046 and 
docket number NIOSH-233-C, by either of the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
     Mail: National Institute for Occupational Safety and 
Health, NIOSH Docket Office, 1090 Tusculum Avenue, MS C-34, Cincinnati, 
Ohio 45226-1998.
    Instructions: All information received in response to this notice 
must include the agency name and docket number (CDC-2020-0046; NIOSH-
233-C). All relevant comments, including any personal information 
provided, will be posted without change to https://www.regulations.gov. 
Do not submit comments by email. CDC does not accept comments by email. 
For access to the docket to read background documents or comments 
received, go to https://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: R. Todd Niemeier, Ph.D., National 
Institute for Occupational Safety and Health, MS-C15, 1090 Tusculum 
Avenue, Cincinnati, OH 45226. Telephone: (513) 533-8166.

SUPPLEMENTARY INFORMATION: NIOSH seeks public comments on its 
reevaluations with initial recommendations to change the status of two 
drugs, pertuzumab and liraglutide, on the NIOSH List of Antineoplastic 
and Other Hazardous Drugs in Healthcare Settings (the List). The NIOSH 
reevaluations were conducted based on the process described in the 
NIOSH Procedures for Developing the NIOSH List of Hazardous Drugs in 
Healthcare Settings, available at https://www.cdc.gov/niosh/docs/2016-161/.
    NIOSH reevaluated the placement of pertuzumab on the NIOSH List in 
response to a request for reevaluation from the manufacturer. Based on 
this reevaluation, the initial NIOSH recommendation is to remove 
pertuzumab from the NIOSH List. In its reevaluation NIOSH determined 
that, due to the intrinsic molecular properties of pertuzumab and the 
nature of the specific hazard posed by exposure to pertuzumab, it is 
not likely to pose a hazard to workers in healthcare settings. The 
potential adverse health effect relevant to pertuzumab occupational 
exposure is the increased potential for fetal developmental 
abnormalities due to oligohydramnios during pregnancy [FDA 2012]. 
However, the development of oligohydramnios during pregnancy is 
reversible and would require repeated exposures to pertuzumab that are 
high enough to cause oligohydramnios through the relevant period of 
development. Pertuzumab has limited dermal, oral, and inhalation 
bioavailability due to its intrinsic molecular properties. Repeated 
unintended exposures resulting from needlestick injuries at levels high 
enough to result in sustained oligohydramnios is unlikely. For these 
reasons, pertuzumab is not expected to pose a hazard to workers in 
healthcare workplaces.
    NIOSH reevaluated the placement of liraglutide on the NIOSH List in 
response to a request for reevaluation from the manufacturer. Based on 
this reevaluation, the initial NIOSH recommendation is to remove 
liraglutide from the NIOSH List. In its reevaluation NIOSH determined 
that, due to the intrinsic molecular properties of liraglutide and the 
nature of the specific hazard posed by exposure to liraglutide, it is 
not likely to pose a hazard to workers in healthcare settings. In 
animal studies liraglutide was reported to cause C-cell specific 
thyroid tumors [FDA 2009]. This carcinogenic effect was due to 
mitogenic activity, and the progression required continued liraglutide 
exposure. The relevance of C-cell specific thyroid tumor formation in 
response to liraglutide exposure to humans is unknown but cannot be 
ruled out. Potential fetal developmental abnormalities are also seen in 
some animal studies, and there may be risk to the fetus in pregnant 
patients. However, the intrinsic molecular properties of the 
liraglutide peptide greatly decrease dermal, oral, and inhalation 
bioavailability, and the hazards related to liraglutide exposure would 
require repeated needlestick injuries. Systemic exposures in workplaces 
are not likely to reach levels required for the potential adverse 
effects to pose a hazard.
    In addition to providing the opportunity for public comment, NIOSH 
is conducting external peer review of its reevaluations. NIOSH has 
completed the peer review of pertuzumab and will conduct the peer 
review of liraglutide concurrently with the public review. The charges 
to the public and peer reviewers are provided below.

Public and Peer Review Charge for the Reevaluation of Pertuzumab on the 
NIOSH List of Hazardous Drugs

    The manufacturer's request to reevaluate the inclusion of 
pertuzumab on the NIOSH List proposed that pertuzumab does not present 
a potential hazard to healthcare worker exposures because the 
properties of the drug limit the potential for exposure and therefore 
adverse health effects from that exposure. NIOSH developed a scenario 
for worker exposure to pertuzumab to evaluate this proposal. Based on 
this scenario NIOSH determined that pertuzumab does not meet the NIOSH 
definition of a hazardous drug and recommends that it be removed from 
the List. Please review the NIOSH reevaluation of pertuzumab and 
consider the following questions.
    1. Is this an appropriate method for evaluating the potential for 
exposure to pertuzumab?
    2. Is oligohydramnios the best health effect to evaluate? If not, 
what other health effect(s) should be evaluated and why?

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    3. Is a needlestick injury the only reasonable route of exposure 
for healthcare workers? Please explain.
    4. Are the assumptions about the amount of exposure to pertuzumab 
in a healthcare setting reasonable? Please explain.
    5. Is the determination that the amount of exposure to pertuzumab 
in a healthcare setting does not constitute a hazard for healthcare 
workers reasonably supported by the available scientific information? 
Please explain.
    6. What alternatives could be considered to this approach for 
monoclonal antibodies to characterize the potential hazard to workers?

Public and Peer Review Charge for the Reevaluation of Liraglutide on 
the NIOSH List of Hazardous Drugs

    The manufacturer's request to reevaluate the inclusion of 
liraglutide on the NIOSH List proposed that it does not present a 
potential hazard to healthcare worker exposures because the properties 
of the drug limit the potential for exposure and therefore adverse 
health effects from that exposure. To reevaluate this drug, NIOSH 
reviewed data regarding the hazards and potential for systemic exposure 
to liraglutide. Based on this reevaluation NIOSH determined that 
liraglutide does not meet the NIOSH definition of a hazardous drug and 
recommends that it be removed from the List. Please review the NIOSH 
reevaluation of liraglutide and consider the following questions.
    1. Are the evaluated health effects the appropriate health effects 
to evaluate? If not, what other health effect(s) should be evaluated 
and why?
    2. Are the assumptions about the potential exposures to liraglutide 
in a healthcare setting reasonable? Please explain.
    3. Is the determination that the amount of exposure to liraglutide 
in a healthcare setting does not constitute a hazard for healthcare 
workers reasonably supported by the available scientific information? 
Please explain.
    4. What alternative approaches could be considered to characterize 
the potential hazard to workers from peptide-based drugs?
    5. Is there any additional information that NIOSH should consider 
in its reevaluation of liraglutide?

References

FDA [2009]. Liraglutide Pharmacology Review. Retrieved from https://www.accessdata.fda.gov/scripts/cder/daf/.
FDA [2012]. US Food and Drug Administration Pharmacology Review of 
Perjeta. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/125409Orig1s000PharmR.pdf NIOSH [2016]. 
NIOSH list of antineoplastic and other hazardous drugs in healthcare 
settings, 2016. By Connor TH, MacKenzie BA, DeBord DG, Trout DB, 
O'Callaghan JP. Cincinnati, OH: U.S. Department of Health and Human 
Services, Centers for Disease Control and Prevention, National 
Institute for Occupational Safety and Health, DHHS (NIOSH) 
Publication Number 2016-161. https://www.cdc.gov/niosh/docs/2016-161/ NIOSH [2023]. Procedures for developing the NIOSH list of 
hazardous drugs in healthcare settings. By Whittaker C, Ovesen JL, 
MacKenzie BA, Hartley T, Berry KA, Piacentino J. Cincinnati, OH: 
U.S. Department of Health and Human Services, Centers for Disease 
Control and Prevention, National Institute for Occupational Safety 
and Health, DHHS (NIOSH) Publication No. 2023-129. https://www.cdc.gov/niosh/docs/2023-129/.

John J. Howard,
Director, National Institute for Occupational Safety and Health, 
Centers for Disease Control and Prevention.
[FR Doc. 2024-00693 Filed 1-12-24; 8:45 am]
BILLING CODE 4163-18-P