Data on the developmental effects of itraconazole and ketoconazole suggest developmental toxicity has only been observed in doses greater than the maximum human recommended dose. documents in the last year, 746 Two drugs included in the 2018 FRN, inotuzumab ozogamicin and trabectedin, have MSHI and are automatically added to the 2016 List. Four independent peer reviewers and 55 public commenters offered input on the draft Policy and Procedures; their substantive comments are summarized below, followed by NIOSH responses. While every effort has been made to ensure that Accessed July 16, 2020. 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. It is not an official legal edition of the Federal documents in the last year, 769 The two drugs with MSHI that were placed on the List and the 20 drugs and one drug class proposed for placement on the List were identified in the February 14, 2018 notice, along with NIOSH's rationale for each proposed addition. These three drugs do not appear below because they are not subject to public comment. . NIOSH response: Drugs still under investigation are not included on the List because no scientific information, including information normally provided in package inserts, is available for NIOSH review. One would assume that, in both instances, a great deal of time and thought is expected to provide feedback to NIOSH. However, the remaining parts of the draft policy and procedures mentions that animal studies should be reviewed . All three draft documents are available in the docket for this activity. 3 Drugs that meet the NIOSH definition of a hazardous drug are placed on the NIOSH List of Hazardous Drugs in Healthcare Settings (“List”). Reproductive toxicity: Cited studies in the package insert demonstrated reproductive toxicity in male and female rates. on Links to the draft documents can be found here. Is the threshold of information required to move from the screening process to the full evaluation process clearly described? 2020 NBA Draft predictions including pick-by-pick analysis from CBS Sports NBA experts. In very few cases, if any, would sufficient studies be available to conduct a formal meta-analysis relating to a specific drug. 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. This information is not part of the official Federal Register document. Comment: The List should identify those hazardous drugs that are both cytotoxic and cytostatic as well as volatile. Peer review comment: The frequency of review of the FDA database should be specified earlier in the draft. 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). Darbepoetin alfa should not be placed on the List. documents in the last year, 64 Comment: Botulinum toxins, including abobotulinumtoxinA and onabotulinumtoxinA, should not be placed on the List. 2. NIOSH response: Although NIOSH typically reviews the FDA database on a monthly basis, the draft Procedures no longer specifies or indicates a frequency of database review to allow for flexibility in the event of unforeseen circumstances. However, after consideration of input from the public and stakeholders, NIOSH has decided to review the toxicity and the hazards related to occupational exposure to botulinum toxins. documents in the last year, by the State Department 2020-09332 Filed 4-30-20; 8:45 am], updated on 4:15 PM on Wednesday, December 2, 2020, updated on 8:45 AM on Wednesday, December 2, 2020. documents in the last year, 10 NIOSH does not offer peer reviews for public comment for any scientific publications because the technical and scientific review conducted by independent peer reviewers are not NIOSH products. In a Federal Register notice (FRN) published on February 14, 2018 (83 FR 6563), NIOSH invited the public to participate in the development of the List and the procedures used to develop the List by submitting written views, opinions, recommendations, and/or data. NIOSH should consider whether reliance on the AHFS Class 10:00 (antineoplastic agents) alone “is enough to necessitate Table 1 Start Printed Page 25449inclusion even if a drug does need to be on the NIOSH list.”. NIOSH is adding text to clarify the agency's intent. Two commenters offered editorial suggestions for clarifying language in the draft; although the comments are not summarized here, changes were made to the revised draft Procedures as appropriate.Start Printed Page 25446. Because Start Printed Page 25443Table 1 includes drugs identified as antineoplastic, NIOSH should clarify the rationale and intent of Table 1, since drugs used as antineoplastics, but which are not cytotoxic or genotoxic, as traditional antineoplastics are, have been included. The Procedures should state “that this list is [a] hazard identification and not a risk assessment exercise. NIOSH has determined that grouping all antineoplastic drugs together in one table is no longer the most useful or informative for users. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website. Comment: Bacillus Calmette-Guerin (BCG) should be removed from the List. . For complete information about, and access to, our official publications NIOSH's definition of a hazardous drug only covers drugs approved by FDA's Center for Drug Evaluation and Research and is not considered for inclusion on the, Dihydroergotamine AHFS Class: 5-hydroxytryptamine (HT) receptor binder, Ivabradine AHFS Class: Hyperpolarization-activated cyclic nucleotide-gated (HCN) blocker. Comment: The draft Policy and Procedures should include a methodology describing how NIOSH evaluates monoclonal antibodies. NIOSH response: The daily therapeutic dose at which serious organ toxicity, developmental toxicity, or reproductive toxicity occurs (10 mg/day in human adults and 1 mg/kg per day in laboratory animals) has long been used by the pharmaceutical industry to develop occupational exposure limits (OELs) of less than 10 μg/m[3] after applying appropriate uncertainty factors. These can be useful The safety data sheet for this drug indicates that it does not pose a heightened risk to healthcare workers. For some of these drugs, no drug-specific data were available in the package inserts to support warnings in the inserts regarding developmental or reproductive effects; for other drugs, the toxic effects occurred at doses higher than human recommended doses. NIOSH has formalized the methodology NIOSH uses to guide the addition of drugs to or removal of drugs from the List, in a document entitled Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings (Procedures).1 As stated in the Procedures, NIOSH defines a hazardous drug as a drug that is: 1 NIOSH [2020]. Peer review comment: It may be inappropriate for NIOSH not to place drugs on the List when NIOSH has determined there is insufficient information to support the placement. I wonder whether the current regulatory climate permits NIOSH any level of control over the handling of drugs in this category.”. However, because NIOSH has reaffirmed in the draft Procedures that only those drugs approved by the FDA Center for Drug Evaluation and Research are included in the List, BCG is no longer included in the List. Peer review comment: NIOSH should provide “a more robust description of the evaluation criteria to include that these are shared across a number of other professional organizations and panels which also endorsed these same criteria.”. 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. on 8. Listen to ASHPOfficial episodes free, on demand. Peer review comment: NIOSH should offer an example of why a drug identified as a hazardous drug because it poses as carcinogenic hazard might not be a classified as a carcinogen pursuant to the NIOSH Chemical Carcinogen Policy. NIOSH response: The reviewer has interpreted the NIOSH statement differently than what the agency intended. documents in the last year, by the Centers for Medicare & Medicaid Services A third draft document, Managing Hazardous Drug Exposures: Information for Healthcare Settings, is intended to help employers establish workplace-specific management procedures for hazardous drugs. informational resource until the Administrative Committee of the Federal Peer review comment: NIOSH's discussion of an employer-performed site-based risk assessment to control the risk of exposure is confusing when placed in a document describing NIOSH's hazard identification procedures. NIOSH response: While some drugs may have low bioavailability by relevant routes of exposure due to molecular weight, other factors in the characterization of the hazard are considered as well. As such, the use of animal studies to evaluate the hazardous nature of a drug should be explicitly stated.”. You will be subject to the destination website's privacy policy when you follow the link. As stated in the OMB Final Information Quality Bulletin for Peer Review (Bulletin), “[p]eer reviewers shall be charged with reviewing scientific and technical matters. According to the reviewer, “[t]his approach may not be appropriate if indeed the purpose of the screening is to protect the health and well-being of workers who may be exposed to hazardous drugs. In very few cases, if any, would sufficient studies be available to conduct a formal meta-analysis relating to a specific drug. include documents scheduled for later issues, at the request Accordingly, drugs that sublime should be handled using risk management strategies relevant to the conditions of use. . NIOSH response: In response to input from peer reviewers and external comments and following scientific review, NIOSH proposes a reorganization of the tables in the draft 2020 List in a manner that may address at least some of the concerns expressed. The individuals and organizations who commented on this issue felt that USP's use of the NIOSH List raises the List to the level of a regulatory action, and should include only antineoplastic drugs on Table 1. NIOSH may consider molecular weight along with the other intrinsic molecular properties of a drug that affect the hazard a drug poses. [7] There are no human studies relating to the developmental effects of daratumumab or dinutuximab. Comment: Eight drugs were approved by FDA prior to December 2015, but do not appear on the 2016 List and were not proposed for placement on the List in the February 2018 FRN. NIOSH encourages public input on the question of which ingredient identifier may be the most useful for the List. Table 2 would now contain drugs that meet one or more of the NIOSH hazardous drug criteria and may be developmental and/or reproductive developmental toxins but are not drugs which have MSHI or are classified as carcinogens or probable carcinogens by NTP or IARC. No new information has been reported that would meet the NIOSH criteria for a hazardous drug. The subsequent description of a site risk Start Printed Page 25441assessment does not seem appropriate here. In addition, having an algorithm to determine the strength of a paper will also aid in minimizing any potential inter- and intra-reviewer differences. See USP, FAQs: <800> Hazardous Drugs—Handling in Healthcare Settings, https://www.usp.org/​frequently-asked-questions/​hazardous-drugs-handling-healthcare-settings. . Comment: NIOSH indicated that two drugs—daratumumab and dinutuximab—demonstrated insufficient toxicity information available to meet the NIOSH definition of a hazardous drug. 3. The Federal Docket folder of supporting information behind the NIOSH proposal includes not only a draft of the actual 2020 list and the document on managing drug exposures, but also a draft of the procedures NIOSH used to develop the 2020 list. Document Drafting Handbook About the Federal Register Comments may be submitted, identified by docket numbers CDC-2020-0046 and NIOSH-233-C, by either of the following two methods: Instructions: All information received in response to this notice must include the agency name and the docket numbers (CDC-2020-0046; NIOSH-233-C). Interested parties are invited to participate in this activity by submitting Start Printed Page 25440written views, opinions, recommendations, and/or data. USP added clarification about the application of chapter <800> to hazardous drugs, which can be found on its FAQ page.[4]. NIOSH is proposing to regroup the drugs by hazards. are not part of the published document itself. Fluconazole meets the NIOSH criteria for a hazardous drug while the other two, ketoconazol and itraconazole, do not. 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. Be sure to leave feedback using the 'Feedback' button on the bottom right of each page! NIOSH response: The majority of drug evaluations are based on information provided in the drug package insert; NIOSH relies on the quality of science Start Printed Page 25442generated by a drug manufacturer, subsequently reviewed by FDA during the drug approval process, and then published in the drug package insert. documents in the last year, by the Fish and Wildlife Service b. In addition, darbepoetin alfa did not meet the NIOSH criteria for a hazardous drug based on any other toxicity endpoint. The OFR/GPO partnership is committed to presenting accurate and reliable Learn more here. Hormonal agents that are classified by NTP as “known to be a human carcinogen” or by IARC as “carcinogenic” or “probably carcinogenic” will be identified in Table 1. relative risk, odds ratios, etc. B. Seven commenters asked questions and offered suggestions about the procedures themselves. Animal studies, where available, are also used in our evaluations. Accordingly, NIOSH proposes to place exenatide on the List. Because there is conflicting evidence about the hazard posed by botulinum toxins to the workers who handle these drugs, NIOSH is not proposing the placement of botulinum toxins on the List at this time and invites additional studies, data, and expert opinions pertinent to this issue in order to evaluate the botulinum toxins more fully. 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. NIOSH should provide the rationale for not proposing their placement on the List. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. 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: bmackenzie@cdc.gov. Is the reconsideration process for addition or deletion of a drug to/from the hazardous drug list adequately described? May 2020. 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 announced that the following draft documents were 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. Therefore, in accordance with the draft Procedures some monoclonal antibodies may not meet the NIOSH definition of the term “hazardous drug.” Because the list of drugs proposed for placement on the List has been updated based on the draft Procedures, the monoclonal antibodies bevacizumab and trastuzumab are no longer proposed for placement on the List. Comment: Peer reviews should be conducted before the close of the public comment period to allow public commenters time to review them. When studies are available for review of a drug being considered for placement on the List or for the reevaluation of a drug already on the List, quality may be evaluated by NIOSH scientists and independent peer reviewers on a case-by-case basis. the official SGML-based PDF version on govinfo.gov, those relying on it for Are there any issues not considered by the charge questions that should be addressed. No labeling change has ever resulted in the removal of a drug from the List, but labeling changes that demonstrate a lack of evidence of toxicity would be dealt with in the regular List updates. 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. for better understanding how a document is structured but The rationale for placing interferon beta-1b on the List is that information from the package insert indicated reproductive toxicity: spontaneous abortion in human clinical trials. Therefore, when antineoplastic drugs are grouped, as they were in earlier versions of Table 1, drugs that required different levels of protection were grouped together (non-cytotoxic drugs with cytotoxic drugs). rendition of the daily Federal Register on FederalRegister.gov does not (NIOSH) uses to determine whether a drug 2 meets the criteria in the NIOSH definition of a hazardous drug. The Federal Register Notice for the Draft of the 2020 NIOSH List of Hazardous Drugs is now available. Not allowing public commenters to review peer reviews before submitting their own comments to the docket is “in conflict with the principle of transparency” established in the OMB Final Information Quality Bulletin for Peer Review (70 FR 2664, Jan. 14, 2005). The large molecular size limits dermal absorption and aerosolization. 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. 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 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. better and aid in comparing the online edition to the print edition. Three commenters offered opinions on the timeliness of the List, which NIOSH has attempted to publish every 2 years since 2010. NIOSH has requested public comments on three draft documents: (1) the 2020 List of Hazardous Drugs; (2) Procedures for Developing the NIOSH List (“the List”) of Hazardous Drugs; and (3) Managing Hazardous Drug Exposures For Health Care Settings available here . Both drugs should be placed on the List because information available in the respective package inserts indicates that both drugs may cause teratogenic effects. 4th Edition, (Burlington, MA: Jones & Bartlett). NIOSH response: A drug may be removed from the List based on either a written request from an interested party or a change to the package insert. The last paragraph of this section is particularly confusing to the reader. the document speaks to the need for individual healthcare workplaces to create their own lists of hazardous drugs, but this places the burden of regulation on these institutions themselves, or more likely individuals within these institutions. [1], Fifty-seven submissions were received in docket CDC-2018-0004 (NIOSH-233-B) from 55 commenters (one commenter sent three separate submissions to the docket). The draft Procedures is in the docket for this activity. 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. Embryo-fetal toxicity is shown to happen at dose exposure 1.5 times the recommended ingested human dose of 80 mg; it is unlikely that a healthcare worker would accidentally be exposed to osimertinib during handling at levels found to cause embryo-fetal harm. Thus, neither was proposed for placement on the List in the February 2018 FRN. Accordingly, the List is derived only from drugs approved by FDA's Center for Drug Evaluation and Research. If emailing please type “508 Accommodation PR#9342” without quotes in the subject line of the email. on NIOSH response: NIOSH examines chemical analogs based on similarities in a drug's structure and toxicity profile compared with other drugs on the List. Genotoxicity: Cited studies demonstrated genotoxicity in male rats at high doses (2 grams/kilogram). of the issuing agency. This drug poses no risk to healthcare workers; the evidence supporting its addition is not based on occupational exposure. 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. In the case of a drug being reevaluated, conclusions about study quality would be discussed in a notice published in the Federal Register. legal research should verify their results against an official edition of Peer Review Summaries and NIOSH Responses, Identifying, Screening, Evaluating, and Reviewing a Drug for Placement on the, Reconsideration (Reevaluation) of NIOSH Decisions to Place and Remove Drugs, B. Accordingly, NIOSH is not proposing to place these two drugs on the List. Similarly, small-molecule kinase inhibitors, such as afatinib, crizotinib, dabrafenib, and imatinib, act through a targeted mechanism of action and are not directly cytotoxic; they primarily pose a reproductive and teratogenic risk. Consequently, these drugs are all administered by injection. Comment: What is the mechanism for evaluating investigational new drugs (i.e., drugs used in preclinical and clinical research but not yet FDA-approved)? and includes the following questions. . . Manufacturer recommendation: that females of reproduction potential use effective contraception during and for four months after completing therapy. Peer review comment: NIOSH should clarify “how the threshold dosages (10 mg/day or 1 mg/kg/day) for defining organ toxicity at 'low doses' . 6. on 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. Docket ID: CDC-2020-0046. If so, perhaps this could be referenced with a footnote.”. These tools are designed to help you understand the official document Formerly the “NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings,” the list will be called more simply the “NIOSH List of Hazardous Drugs in Healthcare Settings, 2020.” The list, which is a basic reference document for OSHA, USP and other standard-setting organizations, has not been updated since 2016. Please provide feedback on the overall document: a. Sixteen drugs have been added to NIOSH’s 2020 list, including three for which the manufacturers have provided special handling information. 3. All are open for a 60 day comment period. Information about the application of the List can be found in the introduction of the draft Managing Hazardous Drug Exposures: Information for Healthcare Settings. NIOSH appreciates that a timelier List might be helpful and is working toward that end. .”. documents in the last year, 32 Document page views are updated periodically throughout the day and are cumulative counts for this document. The Federal Register Notice for the Draft of the 2020 NIOSH List of Hazardous Drugs is now available. NIOSH should clarify the criteria described in the footnote and explain how evidence against these various criteria is evaluated, how each independent line of evidence is systematically and critically appraised, how the quality and risk of bias of individual studies is evaluated, how conflicting information is arbitrated, and how the totality of the data is synthesized. Comment. This feature is not available for this document.