One would assume that, in both instances, a great deal of time and thought is expected to provide feedback to NIOSH. Please provide feedback on the overall document: a. Answer: The NIOSH list is not intended to rank hazards. . Comment: NIOSH should conduct or commission a meta-analysis or systematic review, [i]n the absence of published literature synthesizing the body of clinical knowledge about a specific drug. Nine commenters expressed the sentiment that the List would be more useful if it identified drugs that pose a realistic risk to healthcare workers. . . Federal Register issue. . What changes could be made to improve the utility of the information? Comment: FDA-approved drugs should be reviewed in real time or NIOSH should provide off-cycle updates to the List. 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. 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. 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. relative risk, odds ratios, etc. OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. and includes the following questions. documents in the last year, 931 Comment: Monoclonal antibodies do not have a cytotoxic mechanism of action and, as such, do not pose the same level of occupational risk or toxicity as conventional antineoplastic drugs. If you have any questions regarding hazardous drugs please submit them to Email CDC-INFO or call 1-800-CDC-INFO (800-232-4636), TTY: 888-232-6348) 05/01/2023, 858 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. NIOSH does not review drugs that are not yet approved for use in humans. The draft Procedures document is now focused on NIOSH's procedure for identifying hazardous drugs and no longer discusses managing the risk of exposure. Comment: Hazardous drugs should also be identified by UNII code (the unique ingredient identifier used by FDA and USP) on the List. Since its inception, it has been revised to keep up to date with drug development and evolution, and it is undergoing its most recent update. Significant peer review and public comments on the draft Policy and Procedures are summarized and answered below in Section II; public comments on specific drugs are summarized and answered below in Section III. NIOSH does not review biologics reviewed by the FDA Center for Biologics Evaluation and Research. 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. The draft Procedures document is being reorganized to clarify the information NIOSH considers in its evaluations, including relevant animal studies. Information of particular interest includes considerations for design and implementation of a medical surveillance program, data analysis, and communication of results to participants. Aschengrau A, Seage GR [2018], Essentials of Epidemiology in Public Health. c. What information is redundant, incorrect, missing, or not needed? 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. electronic version on GPOs govinfo.gov. corresponding official PDF file on govinfo.gov. 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 Peer Review Agenda, https://www.cdc.gov/niosh/review/peer/isi/healthsafetyrisks.html. In February 2018, NIOSH proposed adding 21 drugs (including one class of drugs) to the List. of the issuing agency. . 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. NIOSH defines HDs as the following: Peer review comment: Following the 60-day period to allow for public and stakeholder consultations, it is unclear if NIOSH will be responding to any parties that have provided comments. on NARA's archives.gov. NIOSH response: Because the draft Procedures document only addresses NIOSH's procedure for identifying hazardous drugs, the Application section is removed. 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. Two drugs included in the 2018 FRN, inotuzumab ozogamicin and trabectedin, have MSHI and are automatically added to the 2016 List. Register documents. Carcinogenicity: Cited studies demonstrated an increased incidence of various oncologic presentations (hepatocellular adenoma/carcinoma, interstitial cell hyperplasia, and uterine endometrial adenocarcinoma), in multiple animal species (rat and mice) at exposure lower than human doses (0.7-1.4 fold in rats and 0.3-0.7 fold in mice compared to a human dosing). Polypeptides of this size and larger have been shown to have bioavailability through relevant routes of exposure. Comment: The List should identify those hazardous drugs that are both cytotoxic and cytostatic as well as volatile. 05/01/2023, 258 USP 800 only states Table 1. is not clearly outlined with respect to the evaluation process. About the Federal Register 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. Which unique ingredient identifier is the most useful for users of the List? 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). NIOSH response: NIOSH applies the same methodology for evaluating each drug approved by the FDA Center for Drug Evaluation and Research, regardless of class. documents in the last year, 9 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. 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. Peer review comment: NIOSH should clarify a sentence concerning NIOSH's preference for human genotoxicity data which states: If available, NIOSH gives preference to those studies. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. These cookies may also be used for advertising purposes by these third parties. NIOSH must add criteria for animal studies to include the recovery/reversibility of adverse effects and the pharmacological relevance of the test species. After considering the peer and stakeholder reviews, NIOSH determined that 20 drugs and one class of drugs exhibit toxicity that meets the NIOSH definition of a hazardous drug and proposed them for placement on the List. 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. As cancer therapy has changed from primarily cytotoxic drugs to non-cytotoxic and targeted therapies, there is sometimes a mismatch in general recommendations for safe handling and the hazardous nature of the drugs. In accordance with the new structure, many of the hormonal agents on the 2016 List have been moved to Table 2. This drug was reviewed by NIOSH for a previous update to the, This drug was reviewed by NIOSH and presented in the 2018 FRN; it did not meet the criteria for a hazardous drug. 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. The agency has updated its List of Hazardous Drugs in Healthcare Settings for 2020 as well as its procedures for developing the list. See https://www.cdc.gov/niosh/topics/hazdrug/peer-review-plan.html for the peer review plan for the draft Policy and Procedures. Comment. Accordingly, NIOSH proposes to place olaparib on the List. The drugs pose the greatest risk to healthcare workers, based on a combination of volatility and dose-related toxic potential of those vapors.. Comments must be received by June 30, 2020. The other 273 were screened and the information available for 44 drugs suggested one or more toxic effects; those drugs were evaluated by NIOSH and shared with peer reviewers and stakeholders. The available information does not demonstrate or support a determination that the drug meets the NIOSH definition of hazardous drug. The chapter describes containment requirements only for HD Active Pharmaceutical Ingredients (APIs) and antineoplastic drugs requiring manipulation. the material on FederalRegister.gov is accurately displayed, consistent with Agenda About USP <800> Potential Risks . 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. 1503 & 1507. The United States Pharmacopeia General Chapter <800> standards focus on controlling occupational exposure to hazardous drugs while also protecting patients. and III.B: bevacizumab, botulinum toxins, darbepoetin alfa, interferon beta-1b, osimertinib, trastuzumab, and triazolam. 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. Ibrutinib was identified as a drug for which the available information shows a toxic effect that does not meet the NIOSH definition of a hazardous drug; blinatumomab was proposed for placement on the List on the basis of evidence which shows the drug is a neurotoxin at low doses. 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. informational resource until the Administrative Committee of the Federal Although assessing specific controls for specific exposure situations is beyond the scope of the List, information about the use of respiratory protection in the handling of hazardous drugs is found in the draft risk management document, Managing Hazardous Drug Exposures: Information for Healthcare Settings, which is available in the docket for this activity. were derived. The USP <800> requirements standardizing the safe handling of hazardous drugs went into effect December 1, 2019. 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. The manufacturer or any other stakeholder is invited to comment on the sufficiency of the explanation of the basis for adding a drug to the List. The drug's mechanism of action does not indicate DNA damage. Peer-reviewed, published studies are usually not available and therefore evaluating the quality of studies is not typically possible. NIOSH determined that grouping all antineoplastic drugs together in one table is no longer the most useful or informative for the user. In addition, having an algorithm to determine the strength of a paper will also aid in minimizing any potential inter- and intra-reviewer differences. developer tools pages. 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. In response to peer reviews and public comments, 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. 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. Genotoxicity has been noted in Chinese hamster ovary cells. on documents in the last year, 825 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. 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. Accordingly, NIOSH primarily uses information available in the package inserts to make determinations about whether to place a drug on the List. Review their work plan and past meeting summaries. NIOSH response: Sublimation depends on the drug form and is not an inherent toxicity property of the drug. documents in the last year, 494 NIOSH has provided its proposed recommendations and related information about controlling hazardous drugs in the Table of Control Approaches in Chapter 8. a. Procedures for Developing the NIOSH List of Hazardous Drugs in Healthcare Settings is intended to formalize the methodology that NIOSH uses to add hazardous drugs to its list. NIOSH response: It is NIOSH practice to respond to all stakeholder and public comments and peer reviews in a Federal Register notice or in a document posted in the relevant NIOSH docket, to maintain a transparent and thorough administrative record. Comment: NIOSH should include the professional qualifications of the NIOSH staff who perform these evaluations. documents in the last year, 83 NIOSH response: For reevaluation of a listed drug, NIOSH does not require requestors to provide a complete analysis of the available evidence. In mice, doses near the maximum recommended human dose lead to increased neonatal death. Does the draft policy and procedures clearly describe the process used by NIOSH to screen and evaluate drugs? Blinatumomab continues to be proposed for placement and other monoclonal antibodies that have properties meeting the NIOSH definition of a hazardous drug will remain on the List. documents in the last year, 153 After review, NIOSH now finds that the information in the package insert for this drug does not support a determination that it presents a hazard to healthcare workers and is no longer proposing to place it on the List. Please explain. Therefore, NIOSH no longer proposes to place osimertinib on the List. The strategies used to manage the risk should match the hazard. NIOSH response: The manufacturer provided information indicating that multiple evaluations of pregnancy registries did not provide any signals suggesting negative pregnancy outcomes associated with interferon beta-1b. 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 NIOSH determined that grouping all antineoplastic drugs together in one table is no longer the most useful or informative for the user. NIOSH also conducted a peer review, with four independent reviewers, of the draft Policy and Procedures.[2]. Antineoplastic cytotoxic medications, anesthetic agents, anti-viral agents, and others, have been identified as hazardous. This is because there is insufficient information to establish an exposure limit and, therefore, one should err on the side of caution and apply the ALARA principle. 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. NIOSH response: Only a few of the drugs on the List are known to have an appreciable vapor pressure; reliable information concerning the vapor pressure of most drugs can be difficult to identify. documents in the last year, 37 All three draft documents are available in the docket for this activity. 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. You can review and change the way we collect information below. This drug poses no risk to healthcare workers; the evidence supporting its addition is not based on occupational exposure. Free Download USP GC <800>Register for live webcastGC <800> Infographic. This information is not part of the official Federal Register document. 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.. Information about the application of the List can be found in the introduction of the draft Managing Hazardous Drug Exposures: Information for Healthcare Settings. bbc winter olympics 2022 commentators,