NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings: Proposed Additions to the NIOSH Hazardous Drug List 2018, 6563-6573 [2018-02957]
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Centers for Disease Control and
Prevention, HHS.
ACTION: Notice of draft document
available for public comment.
AGENCY:
The National Institute for
Occupational Safety and Health
(NIOSH) of the Centers for Disease
Control and Prevention (CDC)
announces the availability for public
comment on the drugs proposed for
placement on the NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings, 2018
(List), as well as the NIOSH Policy and
Procedures for Developing the NIOSH
List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings.
DATES: Comments must be received by
April 16, 2018.
ADDRESSES: Comments may be
submitted, identified by docket numbers
CDC–2018–0004 and NIOSH–233–B, by
either of the following two methods:
• Federal eRulemaking Portal:
www.regulations.gov. Follow the
instructions for submitting comments.
• Mail: NIOSH Docket Office, Robert
A. Taft Laboratories, MS–C34, 1090
Tusculum Avenue, Cincinnati, OH
45226–1998.
Instructions: All information received
in response to this notice must include
the agency name and the docket
numbers (CDC–2018–0004; NIOSH–
233–B). All relevant comments received
will be posted without change to
www.regulations.gov, including any
personal information provided.
FOR FURTHER INFORMATION CONTACT:
Barbara MacKenzie, NIOSH, Robert A.
Taft Laboratories, 1090 Tusculum
Avenue, MS–C26, Cincinnati, OH
45226, telephone (513) 533–8132 (not a
toll free number), Email:
hazardousdrugs@cdc.gov.
SUPPLEMENTARY INFORMATION:
SUMMARY:
Interested parties are invited to
participate in this action by submitting
written views, opinions,
recommendation, and/or data.
Comments are invited on any topic
related to the drugs identified in this
notice, including those evaluated for
This Meeting, open to the
public, has been cancelled.
STATUS:
CONTACT PERSON FOR MORE INFORMATION:
Judith Ingram, Press Officer, Telephone:
(202) 694–1220.
Jkt 244001
NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare
Settings: Proposed Additions to the
NIOSH Hazardous Drug List 2018
I. Public Participation
999 E Street NW, Washington,
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Centers for Disease Control and
Prevention
[CDC–2018–0004; NIOSH–233–B]
PLACE:
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Federal Register / Vol. 83, No. 31 / Wednesday, February 14, 2018 / Notices
placement on the NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings, 2018.
NIOSH also seeks comment on the draft
Policy and Procedures for Developing
the NIOSH List of Antineoplastic and
Other Hazardous Drugs in Healthcare
Settings, available in the docket for this
action. NIOSH invites comments
specifically on the following questions
related to this action:
1. Has NIOSH appropriately identified
and categorized the drugs considered for
placement on the NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings, 2018?
2. Is information available from FDA
or other Federal agencies or in the
published, peer-reviewed scientific
literature about a specific drug or drugs
identified in this notice that would
justify the reconsideration of NIOSH’s
categorization decision?
3. Does the draft Policy and
Procedures for Developing the NIOSH
List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings
include a methodology for reviewing
toxicity information that is appropriate
for this activity?
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II. Background
In September 2004, NIOSH published
NIOSH Alert: Preventing Occupational
Exposures to Antineoplastic and Other
Hazardous Drugs in Health Care
Settings (Alert).1 The 2004 Alert set out
a general NIOSH policy for the
identification of hazardous drugs and
contained examples of U.S. Food and
Drug Administration (FDA)-approved
drugs that were deemed to be hazardous
to workers in health care and other
settings and may require special
handling. This initial list of hazardous
drugs was updated in 2010,2 2012,3
2014,4 and 2016.5 The latest
publication, entitled NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings, 2016
(2016 Update), covered all new
approved drugs and drugs with new
warnings through December 2013.
III. Policy and Procedures for
Developing the NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings
The NIOSH Director has developed
draft policy and procedures, entitled
Policy and Procedures for Developing
the NIOSH List of Antineoplastic and
1 See
https://www.cdc.gov/niosh/docs/2004-165/.
https://www.cdc.gov/niosh/docs/2010-167/.
3 See https://www.cdc.gov/niosh/docs/2012-150/.
4 See https://www.cdc.gov/niosh/docs/2014-138/
default.html.
5 See https://www.cdc.gov/niosh/docs/2016-161/
default.html.
2 See
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Other Hazardous Drugs in Healthcare
Settings, to formalize the methodology
NIOSH uses to guide the addition of
hazardous drugs to the List (see https://
www.cdc.gov/niosh/topics/hazdrug/
default.html). The draft document
clarifies and details the purpose of the
List, which is to assist employers in
providing safe and healthful workplaces
by offering a list of drugs that meet the
NIOSH definition of a hazardous drug,
and sets out the procedures used by
NIOSH to identify such drugs. The draft
policy and procedures will be finalized
after consideration of comments to this
docket and from peer reviewers.6
According to the draft hazardous
drugs policy and procedures, NIOSH
defines a hazardous drug as a drug that
is:
1. Approved for use in humans 7 by
the FDA; 8 and
2. Not otherwise regulated by the U.S.
Nuclear Regulatory Commission; 9 and
3. Either:
a. Accompanied by prescribing
information in the ‘‘package insert’’ 10
that includes special handling
information to protect workers handling
the drug; or
b. Exhibits one or more of the
following types of toxicity in humans,
animal models, or in vitro systems:
Carcinogenicity; teratogenicity or other
developmental toxicity; reproductive
toxicity; organ toxicity at low doses;
genotoxicity; or structure and toxicity
profile that mimics existing drugs
determined hazardous by exhibiting any
one of the previous five toxicity types.
6 See https://www.cdc.gov/niosh/topics/hazdrug/
peer-review-plan.html for the charge to peer
reviewers.
7 Although only drugs approved by the FDA for
use in humans are included in the definition of a
hazardous drug, some of those drugs may be used
in veterinary settings for treatment of animals and
may be a hazard for veterinary care workers.
8 21 U.S.C. 301 et seq.
9 10 CFR parts 19, 20, and 35. See https://
www.nrc.gov/materials/miau/med-use.html.
10 See Drug Advertising: A Glossary of Terms at
https://www.fda.gov/drugs/resourcesforyou/
consumers/prescriptiondrugadvertising/
ucm072025.htm. ‘‘Prescribing information is also
called product information, product labeling, or the
package insert (‘‘the PI’’). It is generally drafted by
the drug company and approved by the FDA. This
information travels with a drug as it moves from the
company to the pharmacist. It includes the details
and directions healthcare providers need to
prescribe the drug properly. It is also the basis for
how the drug company can advertise its drug. The
prescribing information includes such details about
the drug as: Its chemical description; how it works;
how it interacts with other drugs, supplements,
foods, and beverages; what condition(s) or
disease(s) it treats; who should not use the drug;
serious side effects, even if they occur rarely;
commonly occurring side effects, even if they are
not serious; effects on specific groups of patients,
such as children, pregnant women, or older adults
and how to use it in these populations.’’
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In accordance with the draft
hazardous drugs policy and procedures,
NIOSH uses FDA databases to identify
new drug approvals and drugs with new
safety warnings.
Information pertaining to each new
drug and drugs with new safety
warnings is screened to determine
whether a specific drug is potentially
hazardous. Potentially hazardous drugs
are those for which the manufacturer
has provided special handling
information intended to protect
workers, or for which available toxicity
information suggests that a drug may
exhibit one of the types of toxicity in the
NIOSH definition of a hazardous drug.
Drugs for which insufficient toxicity
information is available and drugs for
which the available information
suggests no toxic effect or a toxic effect
that does not meet the NIOSH definition
of a hazardous drug are not proposed for
placement on the List and are not
further considered. Drugs for which
special handling information is
available are published on the NIOSH
website and proposed for placement on
the List; these drugs are not further
evaluated.
Drugs for which the available
information suggests that the drug
exhibits one or more toxic effects that
meet the NIOSH definition of a
hazardous drug are further evaluated to
determine whether the drug should be
proposed for placement on the List. To
conduct the evaluation of drugs for
which information suggests a toxic
effect, NIOSH may consult the following
sources of information to determine
whether each screened drug might
exhibit at least one type of toxicity in
the NIOSH definition of a hazardous
drug:
a. Information in the drug package
insert;
b. FDA information pertaining to new
drug safety labeling changes; 11
c. When available, relevant
information about carcinogenicity from:
(1) The National Toxicology Program
(NTP) within the U.S. Department of
Health and Human Services; 12
(2) U.S. Environmental Protection
Agency (EPA); 13
11 See https://www.accessdata.fda.gov/scripts/
cder/safetylabelingchanges/.
12 NTP (National Toxicology Program, DHHS)
[2016]. 14th report on carcinogens. Research
Triangle Park, NC: U.S. Department of Health and
Human Services, Public Health Service. See https://
ntp.niehs.nih.gov/pubhealth/roc/index-1.html.
13 EPA (Environmental Protection Agency).
Integrated Risk Information System (IRIS)
Assessments. See https://cfpub.epa.gov/ncea/iris2/
atoz.cfm.
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(3) World Health Organization’s
International Agency for Research on
Cancer (IARC); 14 and
(4) NIOSH.15
d. When available, relevant
information about reproductive toxicity,
teratogenicity, or developmental toxicity
from the NTP Center for the Evaluation
of Risks to Human Reproduction
(CERHR), and from its successor, the
Office of Health Assessment and
Translation (OHAT);
e. When available, published, peerreviewed scientific literature about the
hazard potential of a particular drug for
workers in a healthcare setting,
including any relevant studies cited in
the drug package insert; and
f. When available, toxicity
information from Safety Data Sheets
(SDSs) provided by the manufacturer.
Reviewing the available human,
animal, and in vitro data from those
sources, NIOSH uses criteria included
in the hazardous drugs policy and
procedures to determine whether the
available evidence demonstrates or
supports any of the types of toxicity in
the NIOSH definition of a hazardous
drug. NIOSH makes an initial
determination about each drug and then
requests review and comment from
independent peer reviewers.
After consideration of the peer
reviews, NIOSH sorts all screened and
evaluated drugs into one of five
categories:
• Category 1—Special handling
information
• Category 2—Insufficient toxicity
information available to meet the
NIOSH definition of a hazardous drug
• Category 3—Available information
shows no toxic effect or shows a toxic
effect that does not meet the NIOSH
definition of a hazardous drug
• Category 4—Available toxicity
information demonstrates or supports
a determination that the drug does not
meet the NIOSH definition of a
hazardous drug
• Category 5—Available toxicity
information demonstrates or supports
a determination that the drug meets
the NIOSH definition of a hazardous
drug
The categorized drugs are identified
in a Federal Register notice available for
public and stakeholder comment for 60
days.
After consideration of all public and
stakeholder comments received, NIOSH
makes a final determination about the
disposition of all identified drugs and
publishes a notice in the Federal
Register announcing publication of the
NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings,
2018 on the NIOSH website.
IV. Identifying Potentially Hazardous
Drugs
Consistent with the hazardous drugs
policy and procedures described above,
NIOSH consulted two FDA databases on
a monthly basis since the 2016 Update
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to identify newly-approved drugs and
biologics 16 and already-approved drugs
for which the manufacturer has issued
a new safety warning.17 Through the
monthly FDA database search,
conducted from January 2014 through
December 2015, NIOSH identified 74
new drugs that had received FDA
approval and 199 drugs with new safety
warnings. In addition to the drugs
identified by the FDA database searches,
the NIOSH Director received a request
to evaluate two drugs,
dihydroergotamine and isotretinoin, for
placement on the List by an interested
party. In sum, 275 drugs were identified
between January 2014 and December
2015 and screened.
V. Screening of Potentially Hazardous
Drugs
Upon identification by NIOSH, each
drug was screened to determine whether
the manufacturer specified special
handling information in the package
insert or if information in the package
insert suggests that a drug may exhibit
at least one of the types of toxicity in the
NIOSH definition of a hazardous drug.
For 18 drugs, existing toxicity
information did not support placement
on the List (see Table 1) and for 211
drugs and combination drugs, the
available information suggests no toxic
effect or a toxic effect that does not meet
the NIOSH definition of a hazardous
drug (see Table 2); those drugs are not
proposed for placement on the List.
TABLE 1—INSUFFICIENT TOXICITY INFORMATION AVAILABLE TO MEET NIOSH DEFINITION OF HAZARDOUS DRUG
[Category 2]
Belimumab
Betamethasone
Cholic acid
Daratumumab
Desipramine
Dexamethasone
Dinutuximab
Elosulfase
Mepolizumab
Obinutuzumab
Omalizumab
Pegaspargase
Protriptyline
Sebelipase alfa
Secukinumab
Siltuximab
Vedolizumab
Velaglucerase
TABLE 2—AVAILABLE INFORMATION SHOWS A TOXIC EFFECT THAT DOES NOT MEET THE NIOSH DEFINITION OF
HAZARDOUS DRUG
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[Category 3]
Abatacept
Aclidinium
Adalimumab
Adenosine
Aflibercept
Albiglutide
Alcaftadine
Alirocumab
Almotriptan
Anagrelide
Apixaban
Desvenlafaxine
Dexlansoprazole
Diclofenac
Diltiazem
Dimethyl fumarate
Dolasetron
Doripenem
Doxazosin
Doxepin
Doxycycline
Droxidopa
14 IARC Monographs on the Evaluation of
Carcinogenic Risks to Humans, Lyon, France. See
https://monographs.iarc.fr/ENG/Classification/
index.php.
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Ketoconazole
Lamivudine
Lansoprazole
Ledipasvir/Sofosbuvir
Lesinurad
Levetiracetam
Levomilnacipran
Linaclotide
Linagliptin
Lincomycin
Lisinopril
15 NIOSH Carcinogen List. See https://
www.cdc.gov/niosh/topics/cancer/npotocca.html.
16 Drugs@FDA: FDA Approved Drug Products.
https://www.accessdata.fda.gov/scripts/cder/daf/.
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Rasagiline
Regadenosone
Rifaximin
Rilpivirine
Risedronate
Rivaroxaban
Rivastigmine
Rocuronium
Rolapitant
Ropinirole
Rufinamide
17 Drug Safety Labeling Changes. https://
www.accessdata.fda.gov/scripts/cder/safety
labelingchanges/.
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TABLE 2—AVAILABLE INFORMATION SHOWS A TOXIC EFFECT THAT DOES NOT MEET THE NIOSH DEFINITION OF
HAZARDOUS DRUG—Continued
[Category 3]
Aripiprazole
Asenapine
Asparaginase erwinia
Avanafil
Baclofen
Beclomethasone
Dulaglutide
Duloxetine
Edoxaban
Efavirenz
Efinaconazole
Eliglustat
Bedaquiline
Benazepril
Bimatoprost
Boceprevir
Brexpiprazole
Bupivacaine
Buprenorphine
Bupropion
Calcitonin
Canagliflozin
Canakinumab
Cangrelor
Captopril
Carbidopa
Cariprazine
Cefepime
Cefoperazone
Ceftazidime/Avibactam
Ceftriaxone
Cinacalcet
Citalopram
Clindamycin
Clomipramine
Clozapine
Collagenase clostridium histolytica
Dabigatran
Daclatasvir
Dalbavancin
Dalteparin
Dapagliflozin
Dapsone
Daptomycin
Darunavir
Deferasirox
Denosumab
Deoxycholic acid
Eltrombopag
Eluxadoline
Empagliflozin
Escitalopram
Esomeprazole
Etidronate
Evolocumab
Ezopiclone
Fentanyl
Ferumoxytol
Filgrastim
Flibanserin
Fluoxetine
Fluvoxamine
Fondaparinux
Gabapentin
Galantamine
Gemfibrozil
Granisetron
Hydrocodone
Hydrocortisone
Hydromorphone
Ibandronate
Ibrutinib
Imipramine
Infliximab
Ingenol
Insulin degludec
Insulin glargine
Insulin glulisine
Interferon alfa-2b
Interferon beta-1a
Interferon gamma-1b
Ipilimumab
Ivacaftor
Ivermectin
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Finally, the information available for
44 drugs suggests one or more toxic
effects; those drugs were evaluated by
NIOSH, as discussed below, and were
shared with peer reviewers and
stakeholders.18
VI. Evaluation of Potentially Hazardous
Drugs
Consistent with the draft hazardous
drugs policy and procedures, NIOSH
evaluated the 44 drugs identified as
potentially hazardous to determine
whether each meets the NIOSH
definition of a hazardous drug by
exhibiting one or more of the following
18 Historically, NIOSH has conducted peer review
and stakeholder review concurrently, prior to
publication of the list of drugs proposed for
addition to the List. Beginning with the 2020
Update, NIOSH will conduct peer review prior to
publication of the list of drugs proposed for
addition, and will conduct public comment and
stakeholder review concurrently.
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Losartan
Lovastatin
Lumacaftor/Ivacaftor
Maraviroc
Methadone
Methoxy
polyethylene
epoetin beta
Methylphenidate
Methylprednisolone
Minocycline
Mirabegron
Mirtazapine
Morphine
Moxifloxacin
Naloxegol
Natalizumab
Necitumumab
Netupitant/Palonosetron
Nivolumab
Nortriptyline
Olanzapine
Olodaterol
Omeprazole
Ondasetron
Oritavancin
Oxybutynin
Oxycodone
Oxymorphone
Palbociclib
Palonosetron
Panitumumab
Pantoprazole
Paricalcitol
Pegfilgrastim
Peginterferon alpha-2A
Peginterferon alpha-2B
Pembrolizumab
Peramivir
Pramlintide
Prazosin
Rabeprazole
Ramipril
Ramucirumab
types of toxicity in humans, animal
models, or in vitro systems:
Carcinogenicity; teratogenicity or other
developmental toxicity; reproductive
toxicity; organ toxicity at low doses;
genotoxicity; and/or a structure and
toxicity profile of an isomer or close
chemical analog of a drug on the List.
Using criteria articulated in the draft
hazardous drugs policy and
procedures,19 NIOSH reviewed the
available information and sought to
determine whether the evidence for
each drug either demonstrates or
supports a determination of toxicity.
Initial determinations were made about
each evaluated drug and then the list of
evaluated drugs was given to peer
reviewers and stakeholders for
additional evaluation.
19 See
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glycol-
Ruxolitinib
Sacubitril/Valsartan
Sapropterin
Saquinavir
Saxagliptin
Selegiline
Selexipag
Sertraline
Sildenafil
Simeprevir
Simvastatin
Sitagliptin
Sofosbuvir
Somatropin
Sugammadex
Sulfasalazine
Sulfur hexafluoride lipid type-A
Suvorexant
Tadalafil
Taligucerase
Tamsulosin
Tapentadol
Tavaborole
Tedizolide
Telithromycin
Telmisartan
Ticagrelor
Tolvaptan
Trazodone
Triamcinolone
Trimipramine
Trypan blue
Uridine
Vardenafil
Varenicline
Venlafaxine
Vigabatrin
Vilazodone
Vorapaxar
Vortioxetine
Zolpidem
VII. Peer and Stakeholder Review of
Potentially Hazardous Drugs
NIOSH conducted peer and
stakeholder review of all evaluated
drugs.20 Four independent peer
reviewers and eight stakeholders
reviewed and commented on the 44
drugs. De-identified peer and
stakeholder reviews will be placed in
the docket for this action.
VIII. Evaluated Drugs That Do Not Meet
the NIOSH Definition of a Hazardous
Drug
After consideration of the peer and
stakeholder reviews, NIOSH determined
that the available toxicity information
for 23 drugs does not meet the NIOSH
definition of a hazardous drug (Category
20 See https://www.cdc.gov/niosh/review/peer/isi/
hazdrug2018-pr.html for the charge to peer
reviewers.
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4). These drugs are not proposed for
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placement on the List and are identified
in Table 3.
TABLE 3—AVAILABLE TOXICITY INFORMATION DOES NOT DEMONSTRATE OR SUPPORT A DETERMINATION THAT THE DRUG
MEETS THE NIOSH DEFINITION OF A HAZARDOUS DRUG
[Category 4]
Aglucosidase
Alectinib
Alendronate
Alogliptin
Apremilast
Calcipotriene
Cetuximab
Clarithromycin
Diazoxide
Elotuzumab
Finafloxacin
Golimumab
Idelalisib
Isavuconazonium
Itraconazole
Lamotrigine
Lanreotide
Metreleptin
Milnacipran
Nintedanib
Peginterferon beta-1A
Pirfenidone
Tasimelteon
IX. Drugs Proposed for Placement on
the NIOSH List of Hazardous Drugs
NIOSH determined that the available
toxicity information for 20 drugs and
one class of drug demonstrates or
supports a NIOSH determination that
they meet the NIOSH definition of a
hazardous drug are proposed for
placement on the List (Category 5).
These drugs are proposed for placement
on the list and are identified in Table 4.
Two additional drugs have special
handling information specified by the
manufacturer and are proposed for
placement on the List (see Table 4).21
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BILLING CODE 4163–19–P
21 The manufacturers of trabectedin and
inotuzumab ozogamicin added special handling
information to the package inserts after publication
of the 2016 Update. Although these drugs have been
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23:19 Feb 13, 2018
Jkt 244001
categorized by NIOSH as ‘‘hazardous’’ since April
10, 2017, they will be formally added to the 2018
Update unless compelling evidence in support of
not placing them on the List is offered by public
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Generic Drug Name
Rationale for Proposing Placement on the List
Reproductive toxicity and Teratogenicity or other developmental
toxicity: ovarian failure in patients in .clinical trials, embryo-fetal
toxicity in rabbits
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=939b5
d1f-9fb2-4499-80ef-0607aa6b114e
Blinatumomab
Formulation ........................................................ IV
Dosage .................................................. 9 meg/day
AHFS Class ..................................... Antineoplastic
New Drug .........................................................Yes
Special Handling lnformation .......................... No
2018 Update Table No ........................................ 1
Rationale for Proposing Placement on the List
Organ toxicity at low doses: neurotoxicity at low doses in
patients in clinical studies
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=38b48
2a8-960b-4591-985 7-5031 ecb830aa
Botulinum toxins,
all forms including
AbobotulinimtoxinA
and
OnabotulinumtoxinA
Rationale for Proposing Placement on the List
Organ toxicity at low doses and Teratogenicity or other
Formulation....................................................... IM
developmental toxicity: spread of toxin effects, reductions in fetal
Dosage ...............................................1-1000 units
body weight and decreased fetal skeletal ossification at human
AHFS Class ..........................................Neurotoxin
dose
New Drug ................ :·········································No
Special Handling Information ......................... No Package Insert
.2018 Update Table No........................................ 2
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=botufinum+toxin+type+A&pagesize=200&page=1*
Ceritinib
Formulation .............................................. Capsule
Dosage .......................................................750 mg
AHFS Class ..................................... Antineoplastic
New Drug .........................................................Yes
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: embryo-fetal
toxicity at low doses in rats and rabbits
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=fff5d8
05-4ffd-4e8e-8e63-6f129697563e
Clobazam
Jkt 244001
Bevacizumab
Formulation ...................................................... 1V
Dosage ................................................. S-15 mg/kg
AHFS Class~>................................... Antineoplastic
New Drugc .........................................................Yes
Special Handling lnformationd........................ No
2018 Update Table No.e .. c .................... : .............. 1
Formulation ..................... .Tablet, oral suspension
Dosage: ...................................................20 mg/kg
AHFS Ctass ........................................Antiepileptic
New Drug................................................ ,, ........ No
Rationale for Proposing Placement on the List
Reproductive toxicity and Teratogenicity .or other developmental
toxicity: embryo-fetal mortality and other harm at low doses in
rats and rabbits, present in human breast milk
3
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22:07 Feb 13, 2018
Table 4. Drugs Proposed for Placement on the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare
Settings (Category 1 -- Special Handling Information & Category 5 -- Drug Meets the NIOSH Definition of Hazardous Drug)
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Package Insert
https:/ldailymed. nlm. nih.govldailymed/drug Info. cfm?setid=de03b
d69-2dca-459c-93b4-541 fd3e9571 c
Darbepoetin alfa
Formulation ................. :.............................. IV, SQ
Dosage .......................................OAS-2,25 meg/kg
AHFS Class ....................Erythropoiesis stimulator
New Orug ........................................................... No
Special Handling lnformation .................. ,...... No
2018 Update Table No....................................: .... 2
Rationale for Proposing Placement on the List
Carcinogenicity: progression or recurrence of several cancers in
studies of patients with cancer; reduced body weight in offspring
at low doses in rats and rabbits
Package Insert
https://dailymed .nlm. nih .gov/dailymed/drug Info. cfm?setid=Ofd36
cb9~c4f6:-4167 -93c9-8530865db3f9
Dihydroergotamine
Formulation ...................... IV, IM, SQ, nasal spray
Dosage ........................................................... 1 mg
AHFS Class ........................... SHT receptor binder
New Drug .......................................................... No
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 3
Rationale for Proposing Placement on the List
Reproductive toxicity: oxytocic properties at low doses in
humans
Package Insert
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=Dihydroergotamine *
Exenatide
Formulation ......................................................SQ
Oosage .......................: .........................2 mg/week
AHFS Class .........................................Antidiabetic
New .Drug .......................... , ............................... No
Special Handling Information .........................No
2018 Update Table No........................................ 2
Rationale for Proposing Placement on the list
Carcinogenicity and Teratogenicity or other developmental
toxicity: thyroid C-cell tumors in rat studies; adverse fetal effects
in rats and mice
Package Insert
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=Exenatide *
Formulation ........................................................ IV
2
Dosage ............................................ O.S-0.8 mg/m
AHFS Class ..................................... Antineoplastic
New Drug ........................................................ .Yes
Special Handling lnformation ........................ Yes
Rationale for Proposing Placement on the List
Manufacturer special handling information: drug is cytotoxic,
users should follow applicable OSHA handling and disposal
procedures
Package Insert
PO 00000
Rationale for Proposing Placement on the List
Reproductive toxicity and Teratogenicity or other developmental
toxicity: increased post-implantation loss, including total litter
loss in rats at low doses; post-implantation loss and fetal
malformations in humans
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=c3875
79e-cee0-4334-bd1 e-73f93ac1 bde6
lnotuzumab
ozogamicin
Jkt 244001
Cobimetinib
Formulation ................................................. Tablet
Dosage .........................................................60 mg
AHFS Class ..................................... Antineoplastic
New Drug ........................................................ .Yes
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
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22:07 Feb 13, 2018
Special Handling lnformation ... ,.....................No
2018 Update Table No ......................., ................ 3
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Rationale for Proposing Placement on the List
Reproductive toxicity: spontaneous abortions in human clinical
trials
'
Package Insert
https://dailymed .nlm. nih .gov/dailymed/search. cfm?labeltype=a II&
query=lnterferon+beta-1 b
lsotretinoin
Formulation .............................................. Capsule
Dosage ................................................ O.S-1 mg/kg
AHFS Class .............................................. Retinoid
New Drug .......................................................... No
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 3
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: severe fetal
malformations at any dose in humans
Package Insert
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=lsotretinoin *
Iva bra dine
Formulation .................................................Tablet
Dosage .....................................................S-7.5 mg
AHFS Class .......................................HCN blocker
New Drug .. ,.... ,.................................................Yes
Special Handling lnformation ...................... ,.. No
2018 Update Table No......................................... 3
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: embryo~fetal
toxicity and teratogenicity at low doses in rats
Package Insert
https:l/dailymed. nlm: nih .gov/dailymed/drug Info .cfm?setid=920 18
a65-38f6-45f7 -91 d4-a34921 b81 dOd
Lenvatinib
Formulation .............................................. Capsule
Dosage .........................................................24 mg
AHFS Class ..................................... Antineoplastic
New Drug .........................................................Yes
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: embryo-fetal
toxicity at low doses in rats and rabbits; abortifacient in rabbits at
low doses
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=f4bed
d21-efde-44c6-9d9c-b48b78d7ed1 e
Formulation.............................................. Capsule
Dosage ........................ ,....................... ; ........ SO mg
AHFS Class .............................................Antibiotic
New Drug ...................................... ,................. .Yes
Special Handling lnformation .........................No
2018 Update Table No....... :................................. 3
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: fetal death and
teratogenicity at low doses in rats and rabbits
Package .Insert
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=Miltefosine *
Olaparib
Formulation .............................................. Capsule
Rationale for Proposing Placement on the List
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Federal Register / Vol. 83, No. 31 / Wednesday, February 14, 2018 / Notices
Interferon beta-1 b
Formulation................•..................•..................SQ
Dosage ......................................................0.25 mg
AHFS Class .............................. lmmune modulator
NewDrug .......................................................... No
Special Handling lnformation ................ , ........ No
2018 Update Table No.........................................2
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4b1-c775-411 d-b374-8113248b4077
Miltefosine
22:07 Feb 13, 2018
2018 Update Table No ........................................ 1
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VerDate Sep<11>2014
Osimertinib
Formulation................................................. Tablet
Dosage ................. :.......................................80 mg
AHFS Class .....................................Antineoplastic
New Drug ..........................................................Yes
Special Handling Information.........................No
2018 Update Table No........................................ 1
Rationale for Proposing Placement on the List
Teratogenicity or other developmentaltoxicity: embryo-fetal
toxicity and lethality and reduced growth in offspring in rats
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=Se81 b
4a7 -b971-45e1-9c31-29cea8c87ce 7
Sonidegib
Formulation .............................................. Capsule
Dosage ....................................................... 200 mg
AHFS Class ..................................... Antineoplastic
New Drug ........................................................ .Yes
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
Rationale for Proposing Placement on the List
Reproductive toxicity and Teratogenicity or other developmental
toxicity: embryo-fetal toxicity, teratogenesis, and spontaneous
abortions at low doses in rabbits
Package Insert
https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&
query=Sonidegib *
Trabectedin
Formulation ............................................., ........... IV
2
Dosage ................................................... 1.5 mg/m
AHFS Class ................ ·' ...................Antineoplastic
New Drug .........................................................Yes
Special Handling lnformation ....................... .Yes
2018 Update Table No ................................ ,........ 1
Rationale for Proposing Placement on the List
Manufacturer special handling information: drug is cytotoxic,
users should fol.low applicable OSHA handling and disposal
procedures
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=472bd
78e-be17 -4b9d-90f4-9482c3aec9ff
Trastuzumab
Formulation ........................................................ IV
Dosage ................................................... 2-6 mg/kg
AHFS Class ..................................... Antineoplastic
New Drug .......................................................... No
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
Rationale for Proposing Placement on the List
Organ toxicity at low doses and Teratogenicity or other
developmental toxicity: cardiac and pulmonary toxicity in
patients; malformations and neonatal death in patients
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=492db
d b2-077 e-4064-bff3-3 72d6af0a 7a2
Triazolam
Formulation ................... : ............................. Tablet
Rationale for Proposing Placement on the List
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Federal Register / Vol. 83, No. 31 / Wednesday, February 14, 2018 / Notices
Carcinogenicity and Teratogenicity or other developmental
toxicity: myelodysplastic syndrome/acute myeloid leukemia in
patients in clinical studies; embryo-fetal toxicity, post
implantation loss, malformations at low doses in rats
Package Insert
https://dailymed. nlm. nih .gov/dailymed/drug lnfo.cfm?setid=Se31 a
6a9-864f-4aba-8085-37ee1 ddcd499
22:07 Feb 13, 2018
Dosage ...................................................... .400 mg
AHFS Class ..................................... Antineoplastic
New Drug .........................................................Yes
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 1
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6572
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EN14FE18.004</GPH>
Urofollitropin
Mimics existing drugs determined hazardous by exhibiting
teratogenicity or other developmental toxicity: drug is a
benzodiazepine, a class known to cause congenital
malformations and cross placenta in patients
Package Insert
https ://dailymed. nlm. nih.gov/dailymed/search. cfm?la beltype=all&
query=triazolam&pagesize=200&page=1
Formulation ................................................ IM, SQ
Dosage ................................................. 150-450 IU
AHFS Class ............................ Ovulation stimulator
New Drug .......................................................... No
Special Handling lnformation ......................... No
2018 Update Table No ........................................ 3
Rationale for Proposing Placement on the List
Teratogenicity or other developmental toxicity: drug is known to
cause fetal harm in patients
Package Insert
https://dailymed.nlm.nih.gov/dailymed/druglnfo.cfm?setid=9bb87
daf-d 156-504e-adaf-4c21383f8d 16
IM =intramuscular, IV =intravenous, SQ =subcutaneous
AHFS (American Hospital Formulary Service) Pharmacologic-Therapeutic Classification system.
c FDA-approved drug (January 2014-December 2015).
d Manufacturer's package insert statement cautioning that the drug should be handled as hazardous.
• The final NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings is subdivided into three tables: Table 1 contains antineoplastic drugs, including those
with special handling information provided by the manufacturer; Table 2 contains non-antineoplastic drugs, including those with special handling information; and Table 3 contains
non-antineoplastic drugs that primarily have adverse reproductive and/or teratogenic effects.
* Individual package inserts from multiple manufacturers were reviewed.
a
b
Federal Register / Vol. 83, No. 31 / Wednesday, February 14, 2018 / Notices
22:07 Feb 13, 2018
Oosage ............... :......................................0.25 mg
AHFS Class ......................... ·····'······
........ Hypnotic
NewDrug ........ ,... , ............................................. No
Special Handling Information .........................No
2018 Update Table No•....................................... 3
Federal Register / Vol. 83, No. 31 / Wednesday, February 14, 2018 / Notices
BILLING CODE 4163–19–C
published on the NIOSH website and
announced in a Federal Register notice.
X. Drugs Removed From the NIOSH
List of Hazardous Drugs
In a petition to NIOSH in February
2017, the pharmaceutical company
Theravance Biopharma requested the
removal of the drug telavancin from the
NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare
Settings.22 The petition included an
analysis of animal developmental
toxicity studies and argued that
‘‘[p]lacing telavancin in the NIOSH
category of a hazardous drug greatly
overstates the occupational risk to
healthcare workers handling
telavancin.’’ In response, NIOSH
evaluated the information provided in
the petition as well as other sources
provided to NIOSH by the manufacturer
and determined that telavancin does not
meet the NIOSH definition of a
hazardous drug. NIOSH informed users
of the 2016 List of this determination
via a web posting and responded to
Theravance Biopharma with a letter
dated April 12, 2017.23 Accordingly,
telavancin does not appear in the 2018
update to the NIOSH List of
Antineoplastic and Other Hazardous
Drugs in Healthcare Settings. This
decision is considered final.
XI. Final List of Drugs Proposed for
Placement on the NIOSH List of
Hazardous Drugs
After consideration of all public
comments received in the docket for
this action, NIOSH will develop a final
list of drugs to be placed on the NIOSH
List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings,
2018. The 2018 Update will be
Dated: February 8, 2018.
John Howard,
Director, National Institute for Occupational
Safety and Health, Centers for Disease Control
and Prevention.
[FR Doc. 2018–02957 Filed 2–13–18; 8:45 am]
BILLING CODE 4163–19–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Administration for Children and
Families
Submission for OMB Review;
Comment Request
Title: Office of Refugee Resettlement
Cash and Medical Assistance Program
Quarterly Report on Expenditures and
Obligations.
OMB No.: 0970–0407.
Description: The Office of Refugee
Resettlement (ORR) reimburses, to the
extent of available appropriations,
certain non-federal costs for the
provision of cash and medical
assistance to refugees and other eligible
persons, along with allowable expenses
for the administration of the refugee
resettlement program at the State level.
States, Wilson/Fish projects (alternative
projects for the administration of the
refugee resettlement program), and State
Replacement Designees currently
submit the ORR–2 Financial Status
Report in accordance with 45 CFR part
92 and 45 CFR part 74. This proposed
data collection would collect financial
status data (i.e., amounts of
expenditures and obligations) broken
down by the four program components:
6573
Refugee cash assistance, refugee medical
assistance, health screening, and
services for unaccompanied refugee
minors as well as by program
administration. This breakdown of
financial status data on expenditures
and obligations allows ORR to track
program expenditures in greater detail
to anticipate any funding issues and to
meet the requirements of ORR
regulations at 45 CFR 400.211 to collect
these data for use in estimating annual
costs of the refugee resettlement
program. ORR must implement the
methodology at 45 CFR 400.211 each
year after receipt of its annual
appropriation to ensure that the
appropriated funds will be adequate for
assistance to entering refugees. The
estimating methodology prescribed in
the ORR regulations requires the use of
actual past costs by program
component. In the event that the
methodology indicates that
appropriated funds are inadequate, ORR
must take steps to reduce federal
expenses, such as by limiting the
number of months of eligibility for
Refugee Cash Assistance and Refugee
Medical Assistance. This proposed
single-page report on expenditures and
obligations will allow ORR to collect the
necessary data to ensure that funds are
adequate for the projected need and
thereby meet the requirements of both
the Refugee Act and ORR regulations.
Respondents: State Agencies, the
District of Columbia, Replacement
Designees under 45 CFR 400.301(c), and
Wilson-Fish Grantees (State 2 Agencies)
administering or supervising the
administration of programs under Title
IV of the Act.
ANNUAL BURDEN ESTIMATES
Number of
respondents
Number of
responses
per
respondent
Average
burden hours
per response
Total burden
hours
ORR Financial Status Report Cash and Medical Assistance Program, Quarterly Report on Expenditures and Obligations .............................................
daltland on DSKBBV9HB2PROD with NOTICES
Instrument
57
4
1.50
342
Estimated Total Annual Burden
Hours: 342.
Copies of the proposed collection may
be obtained by writing to the
Administration for Children and
Families, Office of Planning, Research
and Evaluation, 330 C Street SW,
Washington, DC 20201. Attention
Reports Clearance Officer. All requests
should be identified by the title of the
information collection. Email address:
infocollection@acf.hhs.gov.
OMB Comment: OMB is required to
make a decision concerning the
collection of information between 30
and 60 days after publication of this
document in the Federal Register.
Therefore, a comment is best assured of
having its full effect if OMB receives it
within 30 days of publication. Written
comments and recommendations for the
proposed information collection should
be sent directly to the following: Office
of Management and Budget, Paperwork
Reduction Project, Email: OIRA_
SUBMISSION@OMB.EOP.GOV, Attn:
22 Harstad EB and Coleman R. Petition of
Theravance Biopharma US, Inc. to Remove
Telavancin from the NIOSH List of Antineoplastic
and Other Hazardous Drugs in Healthcare Settings.
February 28, 2017.
23 NIOSH letter to Eric Harstad and Rebecca
Coleman. April 12, 2017.
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22:07 Feb 13, 2018
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]]>Agencies
[Federal Register Volume 83, Number 31 (Wednesday, February 14, 2018)]
[Notices]
[Pages 6563-6573]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-02957]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
[CDC-2018-0004; NIOSH-233-B]
NIOSH List of Antineoplastic and Other Hazardous Drugs in
Healthcare Settings: Proposed Additions to the NIOSH Hazardous Drug
List 2018
AGENCY: Centers for Disease Control and Prevention, HHS.
ACTION: Notice of draft document available for public comment.
-----------------------------------------------------------------------
SUMMARY: The National Institute for Occupational Safety and Health
(NIOSH) of the Centers for Disease Control and Prevention (CDC)
announces the availability for public comment on the drugs proposed for
placement on the NIOSH List of Antineoplastic and Other Hazardous Drugs
in Healthcare Settings, 2018 (List), as well as the NIOSH Policy and
Procedures for Developing the NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings.
DATES: Comments must be received by April 16, 2018.
ADDRESSES: Comments may be submitted, identified by docket numbers CDC-
2018-0004 and NIOSH-233-B, by either of the following two methods:
Federal eRulemaking Portal: www.regulations.gov. Follow
the instructions for submitting comments.
Mail: NIOSH Docket Office, Robert A. Taft Laboratories,
MS-C34, 1090 Tusculum Avenue, Cincinnati, OH 45226-1998.
Instructions: All information received in response to this notice
must include the agency name and the docket numbers (CDC-2018-0004;
NIOSH-233-B). All relevant comments received will be posted without
change to www.regulations.gov, including any personal information
provided.
FOR FURTHER INFORMATION CONTACT: Barbara MacKenzie, NIOSH, Robert A.
Taft Laboratories, 1090 Tusculum Avenue, MS-C26, Cincinnati, OH 45226,
telephone (513) 533-8132 (not a toll free number), Email:
[email protected].
SUPPLEMENTARY INFORMATION:
I. Public Participation
Interested parties are invited to participate in this action by
submitting written views, opinions, recommendation, and/or data.
Comments are invited on any topic related to the drugs identified in
this notice, including those evaluated for
[[Page 6564]]
placement on the NIOSH List of Antineoplastic and Other Hazardous Drugs
in Healthcare Settings, 2018. NIOSH also seeks comment on the draft
Policy and Procedures for Developing the NIOSH List of Antineoplastic
and Other Hazardous Drugs in Healthcare Settings, available in the
docket for this action. NIOSH invites comments specifically on the
following questions related to this action:
1. Has NIOSH appropriately identified and categorized the drugs
considered for placement on the NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings, 2018?
2. Is information available from FDA or other Federal agencies or
in the published, peer-reviewed scientific literature about a specific
drug or drugs identified in this notice that would justify the
reconsideration of NIOSH's categorization decision?
3. Does the draft Policy and Procedures for Developing the NIOSH
List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings
include a methodology for reviewing toxicity information that is
appropriate for this activity?
II. Background
In September 2004, NIOSH published NIOSH Alert: Preventing
Occupational Exposures to Antineoplastic and Other Hazardous Drugs in
Health Care Settings (Alert).\1\ The 2004 Alert set out a general NIOSH
policy for the identification of hazardous drugs and contained examples
of U.S. Food and Drug Administration (FDA)-approved drugs that were
deemed to be hazardous to workers in health care and other settings and
may require special handling. This initial list of hazardous drugs was
updated in 2010,\2\ 2012,\3\ 2014,\4\ and 2016.\5\ The latest
publication, entitled NIOSH List of Antineoplastic and Other Hazardous
Drugs in Healthcare Settings, 2016 (2016 Update), covered all new
approved drugs and drugs with new warnings through December 2013.
---------------------------------------------------------------------------
\1\ See https://www.cdc.gov/niosh/docs/2004-165/.
\2\ See https://www.cdc.gov/niosh/docs/2010-167/.
\3\ See https://www.cdc.gov/niosh/docs/2012-150/.
\4\ See https://www.cdc.gov/niosh/docs/2014-138/default.html.
\5\ See https://www.cdc.gov/niosh/docs/2016-161/default.html.
---------------------------------------------------------------------------
III. Policy and Procedures for Developing the NIOSH List of
Antineoplastic and Other Hazardous Drugs in Healthcare Settings
The NIOSH Director has developed draft policy and procedures,
entitled Policy and Procedures for Developing the NIOSH List of
Antineoplastic and Other Hazardous Drugs in Healthcare Settings, to
formalize the methodology NIOSH uses to guide the addition of hazardous
drugs to the List (see https://www.cdc.gov/niosh/topics/hazdrug/default.html). The draft document clarifies and details the purpose of
the List, which is to assist employers in providing safe and healthful
workplaces by offering a list of drugs that meet the NIOSH definition
of a hazardous drug, and sets out the procedures used by NIOSH to
identify such drugs. The draft policy and procedures will be finalized
after consideration of comments to this docket and from peer
reviewers.\6\
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\6\ See https://www.cdc.gov/niosh/topics/hazdrug/peer-review-plan.html for the charge to peer reviewers.
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According to the draft hazardous drugs policy and procedures, NIOSH
defines a hazardous drug as a drug that is:
1. Approved for use in humans \7\ by the FDA; \8\ and
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\7\ Although only drugs approved by the FDA for use in humans
are included in the definition of a hazardous drug, some of those
drugs may be used in veterinary settings for treatment of animals
and may be a hazard for veterinary care workers.
\8\ 21 U.S.C. 301 et seq.
---------------------------------------------------------------------------
2. Not otherwise regulated by the U.S. Nuclear Regulatory
Commission; \9\ and
---------------------------------------------------------------------------
\9\ 10 CFR parts 19, 20, and 35. See https://www.nrc.gov/materials/miau/med-use.html.
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3. Either:
a. Accompanied by prescribing information in the ``package insert''
\10\ that includes special handling information to protect workers
handling the drug; or
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\10\ See Drug Advertising: A Glossary of Terms at https://www.fda.gov/drugs/resourcesforyou/consumers/prescriptiondrugadvertising/ucm072025.htm. ``Prescribing information
is also called product information, product labeling, or the package
insert (``the PI''). It is generally drafted by the drug company and
approved by the FDA. This information travels with a drug as it
moves from the company to the pharmacist. It includes the details
and directions healthcare providers need to prescribe the drug
properly. It is also the basis for how the drug company can
advertise its drug. The prescribing information includes such
details about the drug as: Its chemical description; how it works;
how it interacts with other drugs, supplements, foods, and
beverages; what condition(s) or disease(s) it treats; who should not
use the drug; serious side effects, even if they occur rarely;
commonly occurring side effects, even if they are not serious;
effects on specific groups of patients, such as children, pregnant
women, or older adults and how to use it in these populations.''
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b. Exhibits one or more of the following types of toxicity in
humans, animal models, or in vitro systems: Carcinogenicity;
teratogenicity or other developmental toxicity; reproductive toxicity;
organ toxicity at low doses; genotoxicity; or structure and toxicity
profile that mimics existing drugs determined hazardous by exhibiting
any one of the previous five toxicity types.
In accordance with the draft hazardous drugs policy and procedures,
NIOSH uses FDA databases to identify new drug approvals and drugs with
new safety warnings.
Information pertaining to each new drug and drugs with new safety
warnings is screened to determine whether a specific drug is
potentially hazardous. Potentially hazardous drugs are those for which
the manufacturer has provided special handling information intended to
protect workers, or for which available toxicity information suggests
that a drug may exhibit one of the types of toxicity in the NIOSH
definition of a hazardous drug. Drugs for which insufficient toxicity
information is available and drugs for which the available information
suggests no toxic effect or a toxic effect that does not meet the NIOSH
definition of a hazardous drug are not proposed for placement on the
List and are not further considered. Drugs for which special handling
information is available are published on the NIOSH website and
proposed for placement on the List; these drugs are not further
evaluated.
Drugs for which the available information suggests that the drug
exhibits one or more toxic effects that meet the NIOSH definition of a
hazardous drug are further evaluated to determine whether the drug
should be proposed for placement on the List. To conduct the evaluation
of drugs for which information suggests a toxic effect, NIOSH may
consult the following sources of information to determine whether each
screened drug might exhibit at least one type of toxicity in the NIOSH
definition of a hazardous drug:
a. Information in the drug package insert;
b. FDA information pertaining to new drug safety labeling changes;
\11\
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\11\ See https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/.
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c. When available, relevant information about carcinogenicity from:
(1) The National Toxicology Program (NTP) within the U.S.
Department of Health and Human Services; \12\
---------------------------------------------------------------------------
\12\ NTP (National Toxicology Program, DHHS) [2016]. 14th report
on carcinogens. Research Triangle Park, NC: U.S. Department of
Health and Human Services, Public Health Service. See https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html.
---------------------------------------------------------------------------
(2) U.S. Environmental Protection Agency (EPA); \13\
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\13\ EPA (Environmental Protection Agency). Integrated Risk
Information System (IRIS) Assessments. See https://cfpub.epa.gov/ncea/iris2/atoz.cfm.
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[[Page 6565]]
(3) World Health Organization's International Agency for Research
on Cancer (IARC); \14\ and
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\14\ IARC Monographs on the Evaluation of Carcinogenic Risks to
Humans, Lyon, France. See https://monographs.iarc.fr/ENG/Classification/index.php.
---------------------------------------------------------------------------
(4) NIOSH.\15\
---------------------------------------------------------------------------
\15\ NIOSH Carcinogen List. See https://www.cdc.gov/niosh/topics/cancer/npotocca.html.
---------------------------------------------------------------------------
d. When available, relevant information about reproductive
toxicity, teratogenicity, or developmental toxicity from the NTP Center
for the Evaluation of Risks to Human Reproduction (CERHR), and from its
successor, the Office of Health Assessment and Translation (OHAT);
e. When available, published, peer-reviewed scientific literature
about the hazard potential of a particular drug for workers in a
healthcare setting, including any relevant studies cited in the drug
package insert; and
f. When available, toxicity information from Safety Data Sheets
(SDSs) provided by the manufacturer.
Reviewing the available human, animal, and in vitro data from those
sources, NIOSH uses criteria included in the hazardous drugs policy and
procedures to determine whether the available evidence demonstrates or
supports any of the types of toxicity in the NIOSH definition of a
hazardous drug. NIOSH makes an initial determination about each drug
and then requests review and comment from independent peer reviewers.
After consideration of the peer reviews, NIOSH sorts all screened
and evaluated drugs into one of five categories:
Category 1--Special handling information
Category 2--Insufficient toxicity information available to
meet the NIOSH definition of a hazardous drug
Category 3--Available information shows no toxic effect or
shows a toxic effect that does not meet the NIOSH definition of a
hazardous drug
Category 4--Available toxicity information demonstrates or
supports a determination that the drug does not meet the NIOSH
definition of a hazardous drug
Category 5--Available toxicity information demonstrates or
supports a determination that the drug meets the NIOSH definition of a
hazardous drug
The categorized drugs are identified in a Federal Register notice
available for public and stakeholder comment for 60 days.
After consideration of all public and stakeholder comments
received, NIOSH makes a final determination about the disposition of
all identified drugs and publishes a notice in the Federal Register
announcing publication of the NIOSH List of Antineoplastic and Other
Hazardous Drugs in Healthcare Settings, 2018 on the NIOSH website.
IV. Identifying Potentially Hazardous Drugs
Consistent with the hazardous drugs policy and procedures described
above, NIOSH consulted two FDA databases on a monthly basis since the
2016 Update to identify newly-approved drugs and biologics \16\ and
already-approved drugs for which the manufacturer has issued a new
safety warning.\17\ Through the monthly FDA database search, conducted
from January 2014 through December 2015, NIOSH identified 74 new drugs
that had received FDA approval and 199 drugs with new safety warnings.
In addition to the drugs identified by the FDA database searches, the
NIOSH Director received a request to evaluate two drugs,
dihydroergotamine and isotretinoin, for placement on the List by an
interested party. In sum, 275 drugs were identified between January
2014 and December 2015 and screened.
---------------------------------------------------------------------------
\16\ [email protected]: FDA Approved Drug Products. https://www.accessdata.fda.gov/scripts/cder/daf/.
\17\ Drug Safety Labeling Changes. https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/.
---------------------------------------------------------------------------
V. Screening of Potentially Hazardous Drugs
Upon identification by NIOSH, each drug was screened to determine
whether the manufacturer specified special handling information in the
package insert or if information in the package insert suggests that a
drug may exhibit at least one of the types of toxicity in the NIOSH
definition of a hazardous drug. For 18 drugs, existing toxicity
information did not support placement on the List (see Table 1) and for
211 drugs and combination drugs, the available information suggests no
toxic effect or a toxic effect that does not meet the NIOSH definition
of a hazardous drug (see Table 2); those drugs are not proposed for
placement on the List.
Table 1--Insufficient Toxicity Information Available To Meet NIOSH Definition of Hazardous Drug
[Category 2]
----------------------------------------------------------------------------------------------------------------
----------------------------------------------------------------------------------------------------------------
Belimumab Dinutuximab Protriptyline
Betamethasone Elosulfase Sebelipase alfa
Cholic acid Mepolizumab Secukinumab
Daratumumab Obinutuzumab Siltuximab
Desipramine Omalizumab Vedolizumab
Dexamethasone Pegaspargase Velaglucerase
----------------------------------------------------------------------------------------------------------------
Table 2--Available Information Shows a Toxic Effect That Does Not Meet
the NIOSH Definition of Hazardous Drug
[Category 3]
------------------------------------------------------------------------
-------------------------------------------------------
Abatacept Desvenlafaxine Ketoconazole Rasagiline
Aclidinium Dexlansoprazole Lamivudine Regadenosone
Adalimumab Diclofenac Lansoprazole Rifaximin
Adenosine Diltiazem Ledipasvir/ Rilpivirine
Sofosbuvir
Aflibercept Dimethyl fumarate Lesinurad Risedronate
Albiglutide Dolasetron Levetiracetam Rivaroxaban
Alcaftadine Doripenem Levomilnacipran Rivastigmine
Alirocumab Doxazosin Linaclotide Rocuronium
Almotriptan Doxepin Linagliptin Rolapitant
Anagrelide Doxycycline Lincomycin Ropinirole
Apixaban Droxidopa Lisinopril Rufinamide
[[Page 6566]]
Aripiprazole Dulaglutide Losartan Ruxolitinib
Asenapine Duloxetine Lovastatin Sacubitril/
Valsartan
Asparaginase Edoxaban Lumacaftor/ Sapropterin
erwinia Ivacaftor
Avanafil Efavirenz Maraviroc Saquinavir
Baclofen Efinaconazole Methadone Saxagliptin
Beclomethasone Eliglustat Methoxy Selegiline
polyethylene
glycol-epoetin
beta
Bedaquiline Eltrombopag Methylphenidate Selexipag
Benazepril Eluxadoline Methylprednisolo Sertraline
ne
Bimatoprost Empagliflozin Minocycline Sildenafil
Boceprevir Escitalopram Mirabegron Simeprevir
Brexpiprazole Esomeprazole Mirtazapine Simvastatin
Bupivacaine Etidronate Morphine Sitagliptin
Buprenorphine Evolocumab Moxifloxacin Sofosbuvir
Bupropion Ezopiclone Naloxegol Somatropin
Calcitonin Fentanyl Natalizumab Sugammadex
Canagliflozin Ferumoxytol Necitumumab Sulfasalazine
Canakinumab Filgrastim Netupitant/ Sulfur
Palonosetron hexafluoride
lipid type-A
Cangrelor Flibanserin Nivolumab Suvorexant
Captopril Fluoxetine Nortriptyline Tadalafil
Carbidopa Fluvoxamine Olanzapine Taligucerase
Cariprazine Fondaparinux Olodaterol Tamsulosin
Cefepime Gabapentin Omeprazole Tapentadol
Cefoperazone Galantamine Ondasetron Tavaborole
Ceftazidime/ Gemfibrozil Oritavancin Tedizolide
Avibactam
Ceftriaxone Granisetron Oxybutynin Telithromycin
Cinacalcet Hydrocodone Oxycodone Telmisartan
Citalopram Hydrocortisone Oxymorphone Ticagrelor
Clindamycin Hydromorphone Palbociclib Tolvaptan
Clomipramine Ibandronate Palonosetron Trazodone
Clozapine Ibrutinib Panitumumab Triamcinolone
Collagenase Imipramine Pantoprazole Trimipramine
clostridium
histolytica
Dabigatran Infliximab Paricalcitol Trypan blue
Daclatasvir Ingenol Pegfilgrastim Uridine
Dalbavancin Insulin degludec Peginterferon Vardenafil
alpha-2A
Dalteparin Insulin glargine Peginterferon Varenicline
alpha-2B
Dapagliflozin Insulin glulisine Pembrolizumab Venlafaxine
Dapsone Interferon alfa- Peramivir Vigabatrin
2b
Daptomycin Interferon beta- Pramlintide Vilazodone
1a
Darunavir Interferon gamma- Prazosin Vorapaxar
1b
Deferasirox Ipilimumab Rabeprazole Vortioxetine
Denosumab Ivacaftor Ramipril Zolpidem
Deoxycholic acid Ivermectin Ramucirumab
------------------------------------------------------------------------
Finally, the information available for 44 drugs suggests one or
more toxic effects; those drugs were evaluated by NIOSH, as discussed
below, and were shared with peer reviewers and stakeholders.\18\
---------------------------------------------------------------------------
\18\ Historically, NIOSH has conducted peer review and
stakeholder review concurrently, prior to publication of the list of
drugs proposed for addition to the List. Beginning with the 2020
Update, NIOSH will conduct peer review prior to publication of the
list of drugs proposed for addition, and will conduct public comment
and stakeholder review concurrently.
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VI. Evaluation of Potentially Hazardous Drugs
Consistent with the draft hazardous drugs policy and procedures,
NIOSH evaluated the 44 drugs identified as potentially hazardous to
determine whether each meets the NIOSH definition of a hazardous drug
by exhibiting one or more of the following types of toxicity in humans,
animal models, or in vitro systems: Carcinogenicity; teratogenicity or
other developmental toxicity; reproductive toxicity; organ toxicity at
low doses; genotoxicity; and/or a structure and toxicity profile of an
isomer or close chemical analog of a drug on the List. Using criteria
articulated in the draft hazardous drugs policy and procedures,\19\
NIOSH reviewed the available information and sought to determine
whether the evidence for each drug either demonstrates or supports a
determination of toxicity. Initial determinations were made about each
evaluated drug and then the list of evaluated drugs was given to peer
reviewers and stakeholders for additional evaluation.
---------------------------------------------------------------------------
\19\ See section VII.C.
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VII. Peer and Stakeholder Review of Potentially Hazardous Drugs
NIOSH conducted peer and stakeholder review of all evaluated
drugs.\20\ Four independent peer reviewers and eight stakeholders
reviewed and commented on the 44 drugs. De-identified peer and
stakeholder reviews will be placed in the docket for this action.
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\20\ See https://www.cdc.gov/niosh/review/peer/isi/hazdrug2018-pr.html for the charge to peer reviewers.
---------------------------------------------------------------------------
VIII. Evaluated Drugs That Do Not Meet the NIOSH Definition of a
Hazardous Drug
After consideration of the peer and stakeholder reviews, NIOSH
determined that the available toxicity information for 23 drugs does
not meet the NIOSH definition of a hazardous drug (Category
[[Page 6567]]
4). These drugs are not proposed for placement on the List and are
identified in Table 3.
Table 3--Available Toxicity Information Does Not Demonstrate or Support
a Determination That the Drug Meets the NIOSH Definition of a Hazardous
Drug
[Category 4]
------------------------------------------------------------------------
------------------------------------------------------------------------
Aglucosidase Diazoxide Lanreotide
Alectinib Elotuzumab Metreleptin
Alendronate Finafloxacin Milnacipran
Alogliptin Golimumab Nintedanib
Apremilast Idelalisib Peginterferon beta-
1A
Calcipotriene Isavuconazonium Pirfenidone
Cetuximab Itraconazole Tasimelteon
Clarithromycin Lamotrigine
------------------------------------------------------------------------
IX. Drugs Proposed for Placement on the NIOSH List of Hazardous Drugs
NIOSH determined that the available toxicity information for 20
drugs and one class of drug demonstrates or supports a NIOSH
determination that they meet the NIOSH definition of a hazardous drug
are proposed for placement on the List (Category 5). These drugs are
proposed for placement on the list and are identified in Table 4.
Two additional drugs have special handling information specified by
the manufacturer and are proposed for placement on the List (see Table
4).\21\
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\21\ The manufacturers of trabectedin and inotuzumab ozogamicin
added special handling information to the package inserts after
publication of the 2016 Update. Although these drugs have been
categorized by NIOSH as ``hazardous'' since April 10, 2017, they
will be formally added to the 2018 Update unless compelling evidence
in support of not placing them on the List is offered by public
commenters. See https://www.cdc.gov/niosh/docs/2016-161/default.html.
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X. Drugs Removed From the NIOSH List of Hazardous Drugs
In a petition to NIOSH in February 2017, the pharmaceutical company
Theravance Biopharma requested the removal of the drug telavancin from
the NIOSH List of Antineoplastic and Other Hazardous Drugs in
Healthcare Settings.\22\ The petition included an analysis of animal
developmental toxicity studies and argued that ``[p]lacing telavancin
in the NIOSH category of a hazardous drug greatly overstates the
occupational risk to healthcare workers handling telavancin.'' In
response, NIOSH evaluated the information provided in the petition as
well as other sources provided to NIOSH by the manufacturer and
determined that telavancin does not meet the NIOSH definition of a
hazardous drug. NIOSH informed users of the 2016 List of this
determination via a web posting and responded to Theravance Biopharma
with a letter dated April 12, 2017.\23\ Accordingly, telavancin does
not appear in the 2018 update to the NIOSH List of Antineoplastic and
Other Hazardous Drugs in Healthcare Settings. This decision is
considered final.
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\22\ Harstad EB and Coleman R. Petition of Theravance Biopharma
US, Inc. to Remove Telavancin from the NIOSH List of Antineoplastic
and Other Hazardous Drugs in Healthcare Settings. February 28, 2017.
\23\ NIOSH letter to Eric Harstad and Rebecca Coleman. April 12,
2017.
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XI. Final List of Drugs Proposed for Placement on the NIOSH List of
Hazardous Drugs
After consideration of all public comments received in the docket
for this action, NIOSH will develop a final list of drugs to be placed
on the NIOSH List of Antineoplastic and Other Hazardous Drugs in
Healthcare Settings, 2018. The 2018 Update will be published on the
NIOSH website and announced in a Federal Register notice.
Dated: February 8, 2018.
John Howard,
Director, National Institute for Occupational Safety and Health,
Centers for Disease Control and Prevention.
[FR Doc. 2018-02957 Filed 2-13-18; 8:45 am]
BILLING CODE 4163-19-P
