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. 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. The NIOSH definition of a "hazardous" drug is a drug that is: Approved for use in humans11 by the FDA's Center for Drug Evaluation and Research (CDER);12 Not otherwise regulated by the U.S. Nuclear Regulatory Commission;13 and Either: hospital. Because dosage forms can change and new dosage forms may be approved, dosage form is not considered in making List placement determinations. These cookies may also be used for advertising purposes by these third parties. Although there is currently some guidance in the footnotes, it may be worthwhile to consider a more detailed evaluation process of relevant studies and place it in a more prominent location in the document or possibly as an Appendix.. The draft Procedures document is being reorganized to clarify the information NIOSH considers in its evaluations, including relevant animal studies. 04/30/2020 at 8:45 am. . NIOSH response: A systematic review is a significant undertaking requiring the prior publication or dissemination of multiple studies relating to a specific drug. 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. Workers can be protected from exposures to hazardous drugs through engineering and administrative controls, and proper protective equipment. Accordingly, darbepoetin alfa is no longer proposed for placement on the 2020 List. used to evaluate information from human studies in footnote 44 of the draft Policy and Procedures, no rationale is offered to explain why many of the original nine Bradford Hill criteria are not used. the material on FederalRegister.gov is accurately displayed, consistent with 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 13 drugs proposed for placement on the List are presented for public comment in the table below, along with the rationale for their placement on the List. The size of the molecule limits dermal absorption and aerosolization. Federal Register issue. [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). All three draft documents are available in the docket for this activity. documents in the last year, 931 Drawing conclusions from a methodologically flawed paper can lead to misclassification of a drug. Because the way cancer is treated therapeutically has changed, and the types of drugs used to fight cancer have changed, antineoplastic drugs are no longer all cytotoxic, genotoxic, and highly hazardous chemicals. NIOSH response: After scientific review and consideration of input from peer reviewers and public commenters, NIOSH is proposing a reorganization of the List. Most importantly, the definition of the term hazardous drug would now acknowledge that hazard characterization is an important factor for drugs under consideration. Comment: The drugs ibrutinib and blinatumomab, both antineoplastic monoclonal antibodies, are treated inconsistently in the February 2018 FRN. The draft Procedures document is now focused on NIOSH's procedure for identifying hazardous drugs and no longer discusses managing the risk of exposure. One would assume that, in both instances, a great deal of time and thought is expected to provide feedback to NIOSH. Peer review comment: NIOSH did not include a mechanism to place investigational drugs on the List. on FederalRegister.gov Therefore, when drugs are grouped by their function (i.e., antineoplastic), as they were in earlier versions of Table 1, drugs that required different protective measures were grouped together (non-cytotoxic drugs with cytotoxic drugs). The specific backgrounds of the professional staff engaged in the evaluation process may change over time, but NIOSH is committed to a high-quality process conducted by a team of professionals with the needed knowledge and experience. 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 NIOSH List creates no legal obligation for its users; it is informational, not regulatory, in content. 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. Register (ACFR) issues a regulation granting it official legal status. 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. documents in the last year, 887 2. All relevant comments received will be posted without change to www.regulations.gov,, including any personal information provided. Peer review comment: Some paragraphs in the section entitled, Evidence of Health Effects in Workers from Handling Hazardous Drugs do not belong in the scientific approach section and should be moved to be part of section B Systematic and Sequential Methodology section. Many of the drugs currently used to fight cancer function differently than those previously used. NIOSH response: NIOSH has evaluated each drug individually and not by class of drug. Growing evidence highlights that acute and chronic health effects can occur due to occupational exposure to over 200 hazardous drugs used commonly in healthcare settings. If you are using public inspection listings for legal research, you For example, NIOSH found that ibrutinib had developmental effects in animals but only at doses twice the maximum recommended human dose of 560 mg/day. USP <800> Hazardous Drugs Risk Readiness Checklist Implementation Date December 1, 2019 USP <800> Hazardous Drugs - Handling in Health Care was published on February 1, 2016 with an implementation date of December 1, 2019. NIOSH's extensive review process only allows for periodic updates of hazardous drugs that do not have MSHI. documents in the last year, 1471 Comment: While NIOSH describes several Bradford Hill criteria[6] Please describe what you found to be most or least effective and why. 05/01/2023, 858 In identifying HDs, USP <800> Hazardous Drugs - Handling in Healthcare Settings requires use of the most current version of the list of such drugs maintained by the CDC's National Institute for Occupational Safety and Health (NIOSH). Therefore, NIOSH no longer proposes to place osimertinib on the List. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. when determining the potential for adverse health effects of hazardous drugs in healthcare workers. Please provide information about your professional experience, if any, of implementing control strategies for exposures to hazardous drugs in healthcare or similar settings. Teratogenicity: The package insert contains a warning of embryofetal toxicity when administered to pregnant women. 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. 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. Genotoxicity: Cited studies demonstrated genotoxicity in male rats at high doses (2 grams/kilogram). NIOSH is proposing to regroup the drugs by hazards. The Procedures should state that this list is [a] hazard identification and not a risk assessment exercise. In 1981, after over 10 years of conformational research, the U.S. National Institute of Occupational Safety and Health (NIOSH) issued Recommendations for Safe Handling of Injectable Antineoplastic Drug Products, which recognized inhalation and direct skin contact as high-risk routes of exposure and recommended the use of Class II biosafety Document Drafting Handbook 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. A Notice by the Centers for Disease Control and Prevention on 05/01/2020. If the latter is the case, could a sentence be added to clarify that?. These cookies perform functions like remembering presentation options or choices and, in some cases, delivery of web content that based on self-identified area of interests. NIOSH is seeking input from the public on the draft risk management strategies document and table to ensure that they contain accurate and helpful information. documents in the last year, 24 Peer reviews on the draft Policy and Procedures, as well as NIOSH's responses, are discussed below. For a USP chapter numbered below 1000 to become compendially required, it needs to either be referenced in General Notices, a monograph or another general chapter numbered below <1000>. are not part of the published document itself. While some large molecular weight drugs may have low bioavailability by relevant routes of exposure, other factors in the characterization of the hazard are considered as well. A new peer review was not conducted. Because this issue is a matter of delivery form, rather than inherent toxicity, it is currently beyond the scope of the List. Comment: Dihydroergotamine should not be placed on the List. Table 1. 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. These markup elements allow the user to see how the document follows the on In mice, doses near the maximum recommended human dose lead to increased neonatal death. Throughout the healthcare landscape, people are asking, "What is USP 800?" The safety data sheet for this drug indicates that it does not pose a heightened risk to healthcare workers. the current document as it appeared on Public Inspection on 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. Sargent EV and Kirk GD [1988], Establishing Airborne Exposure Control Limits in the Pharmaceutical Industry, Am Ind Hyg Assoc J 49(6):309-13; Naumann BD and Sargent EV [1997], Setting Occupational Exposure Limits for Pharmaceuticals, Occup Med 12(1):67-80; Sargent EV, Naumann BD, Dolan DG, Faria EC, Schulman L [2002], The Importance of Human Data in the Establishment of Occupational Exposure Limits, Hum Ecol Risk Assess 8(4):805-822. NIOSH response: The List is updated any time NIOSH is aware that a drug manufacturer has added special handling information to the patient information for a specific drug. You will receive an e-mail containing your requested General Chapter downloads after submission. What structural or format changes could be made to improve the utility of this table? See draft Procedures footnote 18, Properties of a drug molecule that may limit adverse effects in healthcare workers are typically chemical, physical and structural properties that affect its absorption (ability to enter the cells of the body), distribution, metabolism, and/or elimination e.g., chemical structure, molecular weight or mass.. CN-20-058-00 In February 2018, NIOSH proposed adding 21 drugs (including one class of drugs) to the List. This document has been published in the Federal Register. Peer review comment: NIOSH should consider a more detailed process when evaluating study quality because [t]he issue related to the quality of a study and, in turn, the strength of data i.e. The draft Policy and Procedures document was developed to formalize the methodology NIOSH uses to guide the addition of hazardous drugs to the List and create a process for requesting the removal from or placement of drugs on the List. The National Institute for Occupational Safety and Health (NIOSH) considers a drug to be hazardous if it exhibits one or more of the following characteristics in humans or animals: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, or structure and toxicity profiles of new drugs that mimic existing hazardous drugs. All information these cookies collect is aggregated and therefore anonymous. This table of contents is a navigational tool, processed from the Interested parties are invited to participate in this activity by submitting Start Printed Page 25440written views, opinions, recommendations, and/or data. These can be useful . 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. Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data. Is the information threshold scientifically sound? CDC twenty four seven. In rats, exenatide administered during the period of organogenesis reduced fetal growth and produced skeletal ossification deficits at doses that approximate the maximum recommended human dose. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. 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. In the February 2018 Request for Comment, NIOSH requested comment on a draft Policy and Procedures for developing the List. NIOSH response: NIOSH has determined that teratogenicity or other developmental toxicity after exposure to osimertinib were observed at doses higher than the maximum recommended human dose and reproductive effects at doses lower than the maximum recommended human doses were equivocal. Comment: Azole antifungal drugs are being treated inconsistently. 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 g/m[3] after applying appropriate uncertainty factors. Reproductive toxicity: The package insert contains MSHI stating, Healthcare providers who are immunocompromised or pregnant should not prepare or administer IMLYGIC and should not come into direct contact with the IMLYGIC injection sites, dressings, or body fluids of treated patients due to the risk of transmission of talimogene laherparepvec and herpetic infection. Spill control. While NIOSH defines criteria and identifies hazardous drugs, USP developed standards for handling these hazardous drugs to minimize the risk to public health. NIOSH must add criteria for animal studies to include the recovery/reversibility of adverse effects and the pharmacological relevance of the test species. NIOSH encourages public comment on these questions. electronic version on GPOs govinfo.gov. 2011; USP 2016, OSHA 2016]. Most were concerned . NIOSH response: NIOSH reviews the relevant data on a drug when a label change is made, not just the data relating to the label change. NIOSH response: NIOSH examines chemical analogs based on similarities in a drug's structure and toxicity profile compared with other drugs on the List. Please include the URL of the site in the Subject line of your email request that you would like to access. Until the ACFR grants it official status, the XML USP General Chapter <800 . The List should also indicate that hazardous drugs that do not sublime may be exhausted through a HEPA filter back into the work area. NIOSH Peer Review Agenda, https://www.cdc.gov/niosh/review/peer/isi/healthsafetyrisks.html. Cited studies in the package insert also demonstrate impaired fertility in rats. 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. . NIOSH has retitled and reorganized the List in response to comments received. 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. Accordingly, drugs that sublime should be handled using risk management strategies relevant to the conditions of use. 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. ET on July 30, 2020 NIOSH response: NIOSH applies the same methodology for evaluating each drug approved by the FDA Center for Drug Evaluation and Research, regardless of class. Comment: The List should identify those hazardous drugs that are both cytotoxic and cytostatic as well as volatile. 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. This site displays a prototype of a Web 2.0 version of the daily These standards apply to all healthcare personnel who receive, prepare, administer, transport or otherwise come in contact with hazardous drugs and all the environments in which they are handled. informational resource until the Administrative Committee of the Federal Comment: What is the mechanism for evaluating investigational new drugs (i.e., drugs used in preclinical and clinical research but not yet FDA-approved)? List of Hazardous Drugs. The List now comprises only two tables: Table 1: Drugs that contain MSHI in the package insert and/or meet the NIOSH definition of a hazardous drug and are classified by NTP as known to be a human carcinogen, or classified by IARC as carcinogenic or probably carcinogenic., Table 2: Drugs that meet the NIOSH definition of a hazardous drug, but do not have MSHI and are not classified by NTP as known to be a human carcinogen, or classified by IARC as carcinogenic or probably carcinogenic.. USP <800> Public comment: Several commenters offered suggestions on the document's use of USP <800>. Saving Lives, Protecting People, The National Institute for Occupational Safety and Health (NIOSH), NIOSH Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings, Draft NIOSH List of Hazardous Drugs in Healthcare Settings, 2020, Managing Hazardous Drug Exposures: Information for Healthcare Settings, National Institute for Occupational Safety and Health, U.S. Department of Health & Human Services. 1. The drugs and rationales for each of them include the following: NIOSH response: Each of these drugs has either been previously reviewed and found not to meet the NIOSH definition of a hazardous drug, falls outside the scope of the List, or is slated for review in the future. offers a preview of documents scheduled to appear in the next day's 05/01/2023, 244 On the contrary, if a party submits a written request for reconsideration, NIOSH will be responding in these instances. Comment: Monoclonal antibodies (i.e., therapeutic proteins) are of such a large molecular weight that they do not pose a realistic risk to healthcare workers. 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. These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. 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. 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. Comment: It is unclear how NIOSH interprets evidence of increasing progression or severity with increased dose, and how the value for low dose was derived. USP 800> Hazardous Drugs-Handling in Healthcare Settings USP <800> Impact on Community Pharmacies Charles Lager RPh, MBA Thursday, April 8, 2021. There are no human studies relating to the developmental effects of daratumumab or dinutuximab. Accordingly, NIOSH proposes to place dihydroergotamine on the List. The purpose of the <800> chapter is to describe practice and quality standards for handling hazardous drugs (HD) in . Reproductive toxicity: Cited studies in the package insert demonstrated reproductive toxicity in male and female rates. Register documents. In humans receiving 400 mg/day or higher developmental effects consistent with animal data have been observed and epidemiological data suggest a risk of spontaneous abortions and congenital abnormalities in infants whose mothers were treated with 150 mg/day fluconazole. 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. documents in the last year, 37 USP General Chapter <800> describes requirements including responsibilities of personnel handling hazardous drugs; facility and engineering controls; procedures for deactivating, decontaminating and cleaning; spill control; and documentation. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Comment: Peer reviews should be conducted before the close of the public comment period to allow public commenters time to review them. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. Please explain. NIOSH considered peer review and public comment received in response to the February 2018 FRN, and significantly revised the draft Policy and Procedures; that document is now called Procedures. 1503 & 1507. The most important criteria for the review of human studies are strength of association, temporality, plausibility, and biological gradient. Draft NIOSH List of Hazardous Drugs in Healthcare Settings, 2020 [PDF - 1 MB] Managing Hazardous Drug Exposures: Information for Healthcare Settings [PDF - 4 MB] Public Comment Period Comments will be accepted until 11:59 p.m. Facility and engineering protocols. NIOSH response: NIOSH views peer review and public comment as two distinct, often complementary, tools in ensuring both quality and transparency in influential scientific information products. This drug is scheduled to be reviewed for the next, Because drugs sold over the counter are not contemplated in this activity, this drug has not been and will not be reviewed for placement on the, This drug was reviewed by NIOSH and presented in the 2018 FRN; the available information shows a toxic effect that does not meet the NIOSH definition of hazardous drug. NIOSH appreciates that a timelier List might be helpful and is working toward that end. The new list format will allow organizations more flexibility for certain drugs when implementing USP General Chapter <800> Hazardous Drugs--Handling in Healthcare Settings. Centers for Disease Control and Prevention, HHS. provide legal notice to the public or judicial notice to the courts. In the case of a drug being reevaluated, conclusions about study quality would be discussed in a notice published in the Federal Register. 8. For this reason, NIOSH encourages individual healthcare settings to develop their own formulary-specific lists of hazardous drugs, which could include investigational drugs that have not yet been approved by FDA. and III.B: bevacizumab, botulinum toxins, darbepoetin alfa, interferon beta-1b, osimertinib, trastuzumab, and triazolam. 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. Draft NIOSH List of Hazardous Drugs in Healthcare Settings, 2020: Summary of Changes, C. NIOSH List of Hazardous Drugs in Healthcare Settings, 2020Title, Reorganization, and Removals, IV. 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. [3] Review their work plan and past meeting summaries. documents in the last year, 1407 In 2010, NIOSH first updated the List based on the NIOSH definition of a hazardous drug. 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. In that case, NIOSH may consider it to be appropriately grouped with carcinogenic drugs, although it would not necessarily meet the criteria for an occupational carcinogen according to the NIOSH Chemical Carcinogen Policy. 2. 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. The value for low dose should be drug-specific and a function of several factors such as normal therapeutic doses, body weight, and length of exposure. Comment: NIOSH should include the professional qualifications of the NIOSH staff who perform these evaluations. . Peer-reviewed, published studies are usually not available and therefore evaluating the quality of studies is not typically possible. 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.
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