The ordering of the tables in the List implies risk stratification; USP <800> supports this impression by requiring heightened handling requirements for Table 1 drugs. Please explain. USP General Chapter <800> provides standards for safe handling of hazardous drugs to minimize the risk of exposure to healthcare personnel, patients and the environment. The goals of these standards are to help increase awareness, provide uniform guidance to reduce the risk of managing hazardous drugs, and help reduce the risk posed to patients and the healthcare workforce. Because the way cancer is treated therapeutically has changed, and the classes of drugs used to fight cancer have changed, antineoplastic drugs are no longer all cytotoxic or genotoxic. NIOSH does not review biologics reviewed by the FDA Center for Biologics Evaluation and Research. . Are these standard or commonly accepted definitions of 'low dose' exposure? NIOSH response: The List is about 4 years behind the introduction of new drugs when it is periodically updated because there are several steps in the review process. This feature is not available for this document. In February 2018, NIOSH proposed adding 21 drugs (including one class of drugs) to the List. electronic version on GPOs govinfo.gov. Reproductive toxicity: Cited studies in the package insert demonstrated reproductive toxicity in male and female rates. NIOSH determined that grouping all antineoplastic drugs together in one table is no longer the most useful or informative for the user. Please include the URL of the site in the Subject line of your email request that you would like to access. Although rare, NIOSH notes any labeling changes that could affect the status of a drug that has been previously classified as hazardous. Accordingly, NIOSH proposes to place exenatide on the List. NIOSH has determined that grouping all antineoplastic drugs together in one table is no longer the most useful or informative for users. In the case of a drug being reevaluated, conclusions about study quality would be discussed in a notice published in the Federal Register. NIOSH response: In streamlining the document to make it more focused on NIOSH's procedures for identifying hazardous drugs, information on controlling the risk of hazardous drug exposure in the workplace was moved to the draft NIOSH document Managing Hazardous Drug Exposures: Information for Healthcare Settings. 8. offers a preview of documents scheduled to appear in the next day's Please provide any additional studies or scientific information related to the use of a medical surveillance program as an additional approach to protect workers in healthcare settings. Because dosage forms can change and new dosage forms may be approved, dosage form is not considered in making List placement determinations. NIOSH's extensive review process only allows for periodic updates of hazardous drugs that do not have MSHI. NIOSH response: NIOSH relies on a range of knowledge, experience, and skills to evaluate drugs for placement on the List, including but not limited to pharmacology, toxicology, medicine, and risk evaluation. The safety data sheet for this drug indicates that it does not pose a heightened risk to healthcare workers. No new information has been reported that would meet the NIOSH criteria for a hazardous drug. NIOSH response: Sublimation depends on the drug form and is not an inherent toxicity property of the drug. A Notice by the Centers for Disease Control and Prevention on 05/01/2020. See https://www.cdc.gov/niosh/docs/2016-161/default.html for all drugs with special handling information added to the 2016 List. Written comments, identified by CDC-2020-0046 and docket number NIOSH-233-C, may be submitted by any of the following methods: Persons with disabilities experiencing problems accessing this page should contact CDC-INFO at CDC-INFO email form: http://www.cdc.gov/info/, 800-232-4636 or the TTY number at (888) 232-6348 and ask for a 508 Accommodation PR#9342. Animal data on the developmental effects of fluconazole suggest developmental changes in rats at doses less than the equivalent maximum human recommended dose of 400 mg/day. NIOSH response: FDA-approved drugs generally have a reasonable body of toxicity information because the manufacturers are required by FDA to provide this information to ensure patient safety when seeking approval for their drugs. The National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention (CDC), in the Department of Health and Human Services announces that the following draft documents are available for public comment: (1) NIOSH Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings (Procedures); (2) NIOSH List of Hazardous Drugs in Healthcare Settings, 2020 (List), including those drugs proposed for placement on the 2020 List, and (3) Managing Hazardous Drug Exposures: Information for Healthcare Settings. corresponding official PDF file on govinfo.gov. Changes to the List structure would place all drugs that meet the NIOSH definition of a hazardous drug and contain MSHI in the package insert and/or are classified by the National Toxicology Program (NTP) as known to be a human carcinogen, or classified by the International Agency for Research on Cancer (IARC) as carcinogenic or probably carcinogenic on Table 1. NIOSH response: For reevaluation of a listed drug, NIOSH does not require requestors to provide a complete analysis of the available evidence. This table of contents is a navigational tool, processed from the Please refer to the current edition of the USP-NF for official text. The President of the United States manages the operations of the Executive branch of Government through Executive orders. These can be useful Risk Management for Hazardous Drugs in Healthcare Settings, https://www.federalregister.gov/d/2020-09332, MODS: Government Publishing Office metadata, https://www.cdc.gov/niosh/docs/2016-161/default.html, https://www.cdc.gov/niosh/topics/hazdrug/peer-review-plan.html, https://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings, https://www.cdc.gov/niosh/review/peer/isi/healthsafetyrisks.html. The drug's mechanism of action does not indicate DNA damage. These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. Drawing conclusions from a methodologically flawed paper can lead to misclassification of a drug. Accordingly, the List is derived only from drugs approved by FDA's Center for Drug Evaluation and Research. 8. were derived. As such, they should be moved from Table 1 to another place on the List. The last paragraph of this section is particularly confusing to the reader. Often the mechanism of action for the drug being assessed is known and can be compared to other drugs of a similar structure/activity. NIOSH may conduct a meta-analysis or systematic review when reevaluating the placement of a drug already on the List, if the available evidence warrants such a review. NIOSH response: NIOSH has determined that dihydroergotamine has demonstrated reproductive toxicity in experimental animals. Section C of the draft Procedures, which includes the evaluation criteria, would be expanded to include new clauses 4 and 5 to allow NIOSH to consider additional factors beyond the intrinsic toxicity of the drug molecule in determining whether to place the drug on the List. In light of these changes, NIOSH proposes a new List structure, described in the preamble to the draft List, which is available for review in the docket for this activity. In addition, having an algorithm to determine the strength of a paper will also aid in minimizing any potential inter- and intra-reviewer differences. ET on July 30, 2020. Answer: The NIOSH list is not intended to rank hazards. Antineoplastic cytotoxic medications, anesthetic agents, anti-viral agents, and others, have been identified as hazardous. The draft Managing Hazardous Drug Exposures: Information for Healthcare Settings, which is in the docket for this activity, is intended to assist employers in establishing their own hazardous drugs management procedures specific to their workplace. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. NIOSH also sought comment on a draft Policy and Procedures for Developing the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings (Policy and Procedures). . Peer review comment: NIOSH should clarify whether a drug may be removed from the List based on changes to the package insert, or if written requests from interested parties to the NIOSH Director are the only mechanism for consideration of a drug for deletion from the List (the reconsideration process as described). Agenda About USP <800> Potential Risks . 05/01/2023, 858 The need to help ensure a quality environment and to protect healthcare personnel from hazardous drugs has been a topic of concern for decades. The hazards of the drugs in Table 1 will relate to carcinogenicity or some other identified hazard by the manufacturer, usually genotoxicity/cytotoxicity. Document page views are updated periodically throughout the day and are cumulative counts for this document. The available information does not demonstrate or support a determination that the drug meets the NIOSH definition of hazardous drug. regulatory information on FederalRegister.gov with the objective of NIOSH response: NIOSH is reorganizing and streamlining the document to make it more easily understood and to move information on site risk assessment to a separate draft document, Managing Hazardous Drug Exposures: Information for Healthcare Settings. Not refining the List to identify real risks of occupational exposure could lead to overwarning for drugs that present little or no workplace risk. . CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Because drugs with MSHI are automatically placed on the List and are not subject to public or peer review, polatuzumab vedotin was added to the 2016 List in September 2019 and will appear in the 2020 List. Genotoxicity: Cited studies demonstrated genotoxicity in male rats at high doses (2 grams/kilogram). Therefore, when antineoplastic drugs are grouped as they were in earlier versions of Table 1 of the List, an appearance that these drugs pose the same hazard was inadvertently created (i.e., non-cytotoxic drugs with cytotoxic drugs). Commenters included pharmacists, professional organizations and associations, pharmaceutical manufacturers, medical centers and/or health systems, individuals who provided their names but not their affiliations, a company that provides risk assessments, a drug database, an insurance company, a medical school professor, a neurologist, and an anonymous commenter. This repetition of headings to form internal navigation links Those monoclonal antibodies that are not directly cytotoxic or conjugated with a cytotoxic agent should be moved from Table 1 to another place on the List. From an occupational hygiene perspective, if there is no existing occupational exposure limit or threshold limit value for a chemical hazard, the best practice is to ensure that worker exposure to the chemical remains As Low As Reasonably Achievable (ALARA). 5. hazardous drugs. of the issuing agency. In embryo-fetal development studies of dihydroergotamine mesylate nasal spray, intranasal administration to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weights and/or skeletal ossification at doses approximately 0.4-1.2 times the exposures in humans receiving the maximum recommended daily dose of 4 mg or greater. NIOSH response: As presented in the 2018 FRN, daratumumab and dinutuximab were reviewed and did not meet the NIOSH criteria for a hazardous drug because the available information about each drug's toxicity was insufficient to support placement on the List. Moreover, NIOSH is not properly weighing the low therapeutic index of the drug against the relatively low risk of handling the drug by healthcare workers who are knowledgeable about safe handling. In my opinion, a review of any animal studies should be conducted as they may offer insight regarding the potential risk posed by a drug. In accordance with the new structure, many of the hormonal agents on the 2016 List have been moved to Table 2. 6. NIOSH response: NIOSH applies the same methodology for evaluating each drug approved by the FDA Center for Drug Evaluation and Research, regardless of class. Each document posted on the site includes a link to the Comment: NIOSH should clarify how close chemical analogs are identified, and whether NIOSH establishes site concordance across analogs and how evidence for and against the absence of concordance is interpreted. One additional drug, polatuzumab vedotin, was approved by FDA's Center for Drug Evaluation and Research in July/August 2019 and its package insert includes MSHI provided by the drug's manufacturer. See USP, FAQs: <800> Hazardous DrugsHandling in Healthcare Settings, https://www.usp.org/frequently-asked-questions/hazardous-drugs-handling-healthcare-settings. Comment: NIOSH should identify those drugs that pose a realistic risk to healthcare workers by considering such occupation exposure factors as drug type (e.g., small molecule, biologic), stability, dosage form, and route of exposure, and then evaluating them against the toxicity criteria. Until the ACFR grants it official status, the XML and III.B: bevacizumab, botulinum toxins, darbepoetin alfa, interferon beta-1b, osimertinib, trastuzumab, and triazolam. 2. NIOSH created and periodically updates the List to assist employers in providing safe and healthful workplaces by offering a list of drugs that meet the NIOSH definition of a hazardous drug. [7] At this time, NIOSH has chosen not to list any of the identification numbers but is considering doing so in the future. is not clearly outlined with respect to the evaluation process. Carcinogenicity/teratogenicity: Cited studies demonstrated an increased incidence of hepatocellular adenomas in mice. c. What information is redundant, incorrect, missing, or not needed? On the contrary, if a party submits a written request for reconsideration, NIOSH will be responding in these instances. Fluconazole is included in the List on Table 3, but for two newer azole antifungals, the available information showed a toxic effect that does not meet the NIOSH definition of a hazardous drug (ketoconazole) and information does not demonstrate or support that the drug meets the NIOSH definition (itraconazole) in the FRN. This clearly infers human studies only. The Public Inspection page may also Self-Regulatory Organizations; NYSE Arca, Inc. Economic Sanctions & Foreign Assets Control, Smoking Cessation and Related Indications, Labeling of Plant-Based Milk Alternatives and Voluntary Nutrient Statements, Authority To Order the Ready Reserve of the Armed Forces to Active Duty To Address International Drug Trafficking, Revitalizing Our Nation's Commitment to Environmental Justice for All, Centers for Disease Control and Prevention, DRAFT - Managing Hazardous Drug Exposures: Information for Healthcare Settings, DRAFT - NIOSH List of Hazardous Drugs in Healthcare Settings, 2020. NIOSH will consider identifying hazardous drugs that are known to be volatile in future updates to the List. The fact that FDA has requirements for reporting of relevant safety related data supports the NIOSH presumption that a lack of information on an endpoint indicates a lack of concern for a specific type of hazard. USP <800> requires an assessment of risk, which is a consideration of the type of HD, dosage form, risk of exposure, packaging, and manipulation. Consequently, these drugs are all administered by injection. These changes now reflected in the draft Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings (draft Procedures) include the clarification of some language and streamlining the procedures NIOSH uses to determine the hazard potential of a specific drug. Thank you for taking the time to confirm your preferences. documents in the last year, by the Food and Drug Administration Botulinum toxins do not meet the criteria for placement on the List; abotulinumtoxinA and rimabotulinumtoxinB did not have labeling changes during the search period January 2014 through December 2015, and changes to the labels for onabotulinumtoxinA and incobotulinumtoxinA do not meet the criteria for organ toxicity at low doses or teratogenicity or other developmental toxicity. [3] Animal studies, where available, are also used in our evaluations. Additionally, peer reviews provide the Agency with a review of its science; peer reviewers and their credentials are identified in the NIOSH Peer Review Agenda.Start Printed Page 25445, Commenters: NIOSH should identify the criteria used to evaluate study quality and strength, and describe how they are used to critically appraise the quality and risk of bias and other limitations of individual studies; arbitrate conflicting information; and synthesize the totality of animal and human studies data in support of, or opposition to, the listing of a drug as hazardous.. From my perspective, as a minimum, this should include porters, ward aides and unit clerks.. NIOSH response: NIOSH's rationale for proposing the placement of triazolam on the List was that it mimics the benzodiazepines which are included on the List because they are teratogenic or cause other developmental effects. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. After evaluating public comments, NIOSH made the following determination: 13 drugs are proposed for placement on the List, 3 drugs are automatically added to the List because they have MSHI in the package insert (2 drugs identified in the 2018 FRN and another recently-approved by FDA), 7 drugs proposed for placement on the List in the 2018 FRN are no longer considered in this action. Two reviewers had questions about the information thresholds required to evaluate drugs, and all reviewers had editorial suggestions for improving the clarity of the draft. . NIOSH response: In 2004, NIOSH used lists from several organizations as examples of hazardous drugs.