Peer Review: List of Hazardous Drugs in Healthcare Settings 2019
Title: NIOSH List of Hazardous Drugs in Healthcare Settings 2019 (formerly titled NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2018)
Anticipated Date of Dissemination: December 2019
Subject: Hazardous Drug Exposure in Healthcare Settings
Purpose: To provide healthcare workers and healthcare facilities information on identifying hazardous drugs so that proper handling can be performed to reduce worker exposures.
Type of Dissemination: Influential Scientific Information
Timing of Review: September 4, 2017 – October 13, 2017
Primary Disciplines or Expertise Needed for Review: toxicology, industrial hygiene, occupational medicine, oncology nursing practices and pharmacy practices
Type of Review: Individual letters
Number of Reviewers: 4 — 10
Reviewers Selected by: CDC/NIOSH
Public Nominations Requested for Review Panel: No
Opportunities for the Public to Comment: Yes, Publication of a request for public comments
Peer Reviewers Provided with Public Comments Before Their Review: No
NIOSH will review all individual comments from the peer reviewers and post a list of proposed additions to the Federal Register for public comment. NIOSH will then make decisions about updating the list based on all comments.
The proposed changes to the list will then be placed on the NIOSH Docket.
Charge to Peer Reviewers
The NIOSH Hazardous Drug Committee has reviewed all new FDA drug approvals and new drug warnings for the period January 2014 through December 2015. The committee reviewed 73 new drug approvals and 198 drugs with new 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. NIOSH identified 44 drugs as potentially hazardous for review by the peer reviewers.
We are requesting that as a peer reviewer, you review the list of drugs that NIOSH suggests be added to the list or not added to the list and provide your evaluations and comments on the Word document provided. Please return your reviews by October 13, 2017 to Barbara MacKenzie at bmackenzie@cdc.gov.
Criteria for NIOSH Hazardous Drug Review
NIOSH Definition of a Hazardous Drug
- Carcinogenicity
- Teratogenicity or other developmental toxicity††
- Reproductive toxicity††
- Organ toxicity at low doses††
- Genotoxicity‡‡
- Structure and toxicity profiles of new drugs that mimic existing drugs determined
††All drugs have toxic side effects, but some exhibit toxicity at low doses. The level of toxicity reflects a continuum from relatively nontoxic to production of toxic effects in patients at low doses (for example, a few milligrams or less). For example, a daily therapeutic dose of 10 mg/ day or a dose of 1 mg/kg per day in laboratory animals that produces serious organ toxicity, developmental toxicity, or reproductive toxicity has been used by the pharmaceutical industry to develop occupational exposure limits (OELs) of less than 10 μg/m3 after applying appropriate uncertainty factors [Sargent and Kirk 1988; Naumann and Sargent 1997; Sargent et al. 2002]. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. Under all circumstances, an evaluation of all available data should be conducted to protect health care workers.
‡‡In evaluating mutagenicity for potentially hazardous drugs, responses from multiple test systems are needed before precautions can be required for handling such agents. The EPA evaluations include the type of cells affected and in vitro versus in vivo testing [51 Fed. Reg. 34006– 34012 (1986)].
General guidance
Our goal is to conduct a hazard identification. We do not conduct a risk assessment.
However, we take into account the dose for animal testing for reproductive and developmental toxicity and carcinogenicity testing. If adverse effects are observed near, at, or below the maximum recommended human dose (MRHD), we consider it to be highly relevant. If doses producing an adverse effect are many time the MRHD, we usually do not consider them in our evaluation.
In addition to dose, for carcinogenicity testing we look for tumors in more than one species and sex. We look for tumors in multiple organs and we look for tumors that are not rodent-specific. Any available human data are considered significant.
For genotoxicity effects, we look at in vivo testing over in vitro testing. However, adverse outcomes in several in vitro tests may be considered in our evaluation.
For reproductive and developmental effects we note if there was maternal toxicity in addition to the dose. Effects on the fetus in the absence of maternal toxicity are considered relevant. Drugs with an FDA pregnancy category X rating are typically listed as hazardous. Drugs in Category D are often listed as hazardous, but it will depend on the individual drug. Any available human data are considered significant.
For organ toxicity, the low dose criterion in the definition is used as a benchmark.
Drugs with manufacturer’s safe handling guidelines are usually put on the list as the manufacturer has decided they are hazardous enough to warrant special handling. Therefore, drugs with manufacturers’ safe handling recommendations do not require review.
Basis for recommendation
A “significant” adverse effect in one of these criteria is usually considered enough to list a drug as hazardous. However, less strong evidence in two or three criteria is sometimes sufficient to list a drug as hazardous.
Box labeled “Decision Criteria”
Please list the factors that led to your decision of “yes” or “no” to listing as hazardous.
Be aware that you CAN indicate that you think a drug should only be listed in Table 3 (reproductive hazard)
Tables to collect Peer Reviewer’s Comments pdf icon[PDF – 179 KB]
Peer Reviewers’ Comments and NIOSH’s Responses
NIOSH requested individual comments from peer reviewers via letters. There was no meeting convened for this review. For each drug, comments from individual peer reviewers are provided in a combined listing format after each of the NIOSH Hazardous Drug criteria. Comments are not attributed to individual peer reviewers. The response to the peer reviewers’ comments is provided for each drug and is the rationale for proposing to place or not to place a drug on the List. This determination was made by the NIOSH Hazardous Drugs Committee after consideration of the NIOSH committee’s evaluation and the individual peer review comments.
Reviewers Comments and NIOSH responseexternal icon
Peer Reviewers
Michael Andrew Maier, M.S., PhD., CIH, DABT
Director, Center for Excellence in Risk and Exposure Science and Education
University of Cincinnati
Department of Environmental Health
Agnes Ann Feemster, Pharm.D., BCPS
Assistant Dean, Experiential Learning Program
Assistant Professor, Pharmacy Practice Management and Leadership
Oncology Medication Safety Officer- The Johns Hopkins Hospital
Department of Pharmacy Practice and Science
University of Maryland School of Pharmacy
Marty Polovich PhD, RN, AOCN
Byrdine F. Lewis School of Nursing and Health Professions
Georgia State University
Melissa A. McDiarmid, MD, MPH, DABT
University of Maryland
School of Medicine
Occupational Health Project