[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]
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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.
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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.
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\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.
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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.
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2. Not otherwise regulated by the U.S. Nuclear Regulatory
Commission; \9\ and
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\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\
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\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.
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(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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(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 http://monographs.iarc.fr/ENG/Classification/index.php.
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(4) NIOSH.\15\
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\15\ NIOSH Carcinogen List. See https://www.cdc.gov/niosh/topics/cancer/npotocca.html.
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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.
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\16\ Drugs@FDA: 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/.
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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]
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Belimumab Dinutuximab Protriptyline
Betamethasone Elosulfase Sebelipase alfa
Cholic acid Mepolizumab Secukinumab
Daratumumab Obinutuzumab Siltuximab
Desipramine Omalizumab Vedolizumab
Dexamethasone Pegaspargase Velaglucerase
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Table 2--Available Information Shows a Toxic Effect That Does Not Meet
the NIOSH Definition of Hazardous Drug
[Category 3]
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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
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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
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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\
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\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.
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\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.
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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
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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]
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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
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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]
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