usp <800> hazardous drug list 2020

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. Furthermore, animal studies must be evaluated for the recovery/reversibility of effects and the pharmacological relevance of the species studied. As such, they should be moved from Table 1 to another place on the List. The size of the molecule limits dermal absorption and aerosolization. documents in the last year, 29 So, any drugs that were approved after 2015, other than those 10 drugs added on March 23, 2022, must be evaluated by your pharmacy as . documents in the last year, 125 Comment: The List seems to be heavily weighted toward older drugs.Start Printed Page 25444. on OELs in this range are typically established for potent or toxic drugs in the pharmaceutical industry. Fluconazole meets the NIOSH criteria for a hazardous drug while the other two, ketoconazol and itraconazole, do not. This feature is not available for this document. 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. 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. the current document as it appeared on Public Inspection on General Chapter <800> was published on February 1, 2016. If you are using public inspection listings for legal research, you should verify the contents of the documents against a final, official NIOSH response: As presented in the 2018 FRN, NIOSH reviewed cetuximab, ibrutinib, ipilimumab, necitumumab, nintedanib, nivolumab, palbociclib, panitumumab, ramucirumab, and ruxolitinib for placement on the List and, for each, the available information showed a toxic effect that does not meet the NIOSH definition of a hazardous drug. and includes the following questions. . In order to clarify that the List is a hazard identification tool, NIOSH has removed this table from the document. As discussed extensively in the notice published February 14, 2018, NIOSH identified 275 potentially hazardous drugs between January 2014 and December 2015 (83 FR 6563). 2011; USP 2016, OSHA 2016]. NIOSH did not take into account the real risk of occupational exposure or the mechanism of action of this relatively large molecule. . 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. Comment: FDA-approved drugs should be reviewed in real time or NIOSH should provide off-cycle updates to the List. The new risk management document is available for review in the docket for this activity. 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. ET on July 30, 2020. Accordingly, NIOSH continues to propose placing ivabradine on the List. 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. NIOSH should collaborate with healthcare to better understand the implications of identifying certain drugs as hazardous and the cost to implement USP <800>. 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. This criterion is typically only used when toxicity information specific to the drug under evaluation is insufficient or unavailable but is available for the chemical analog. 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. 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.. Because this issue is a matter of delivery form, rather than inherent toxicity, it is currently beyond the scope of the List. NIOSH is adding text in footnote 16 of the draft Procedures to clarify and emphasize the derivation. Although such drugs are not in widespread clinical use, personnel in academic and research-oriented facilities are potentially at risk from exposure to these drugs. daily Federal Register on FederalRegister.gov will remain an unofficial While the Bulletin recognizes the benefit of both forms of input to agencies, it provides agencies with broad discretion in determining how to implement peer review, including timing as it relates to public comment, if applicable. Comment: The language in the section titled Application indicates that the draft Policy and Procedures do not apply to healthcare workers who handle recombinant therapeutic proteins. 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. In addition, darbepoetin alfa did not meet the NIOSH criteria for a hazardous drug based on any other toxicity endpoint. Does the draft policy and procedures clearly describe the process used by NIOSH to screen and evaluate drugs? Therefore, at this time NIOSH is no longer proposing to place the class of botulinum toxins on the 2020 List. 6. of the issuing agency. NIOSH response: Because the draft Procedures document only addresses NIOSH's procedure for identifying hazardous drugs, the Application section is removed. the official SGML-based PDF version on govinfo.gov, those relying on it for 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. 1503 & 1507. Peer review comment: The frequency of review of the FDA database should be specified earlier in the draft. relative risk, odds ratios, etc. for better understanding how a document is structured but 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. documents in the last year, 19 Please provide specific examples. documents in the last year, 24 provide legal notice to the public or judicial notice to the courts. Comments must be received by June 30, 2020. Please provide any additional studies or scientific information that support or validate the use of the NIOSH recommended control strategies or alternative strategies to control exposures to hazardous drugs. The Public Inspection page may also For example, monoclonal antibodies are too large to be absorbed through skin contact, and if ingested, they would be destroyed by digestion; if inhaled, the pulmonary system would prevent absorption. USP is a not-for-profit, science-driven organization that has an established process for convening independent experts in the development and maintenance of healthcare quality standards. NIOSH is adding text to clarify the agency's intent. Telephone: 1-800-CDC-INFO (1-800-232-4636) TTY: 1-888-232-6348 . 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. Comment: Osimertinib should not be placed on the List. 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. Peer reviews on the draft Policy and Procedures, as well as NIOSH's responses, are discussed below. ASHP submitted comments in response to the 2020 draft documents in support of this new format. 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. All three draft documents are available in the docket for this activity. [FR Doc. However, NIOSH did not independently evaluate triazolam. This information is not part of the official Federal Register document. The drug's mechanism of action does not indicate DNA damage. 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: After scientific review and consideration of input from peer reviewers and public commenters, NIOSH is proposing a reorganization of the List. 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. If a meta-analysis or systematic review is warranted for a reevaluation, NIOSH would consider these criteria on a case-by-case basis. when determining the potential for adverse health effects of hazardous drugs in healthcare workers. 8. 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. 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. electronic version on GPOs govinfo.gov. NIOSH response: The NIOSH List creates no legal obligation for its users; it is informational, not regulatory, in content. Comment: NIOSH indicated that 10 drugscetuximab, ibrutinib, ipilmumab, necitumumab, nintedanib, nivolumab, palbociclib, panitumumab, ramucirumab, and ruxolitinibdemonstrated available information that shows a toxic effect that does not meet the NIOSH definition of a hazardous drug. 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.. 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. Thank you for taking the time to confirm your preferences. 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). I wonder whether the current regulatory climate permits NIOSH any level of control over the handling of drugs in this category.. NIOSH defines HDs as the following: This repetition of headings to form internal navigation links Register (ACFR) issues a regulation granting it official legal status. 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. Only when a labeling change results in the addition of MSHI to a package insert will NIOSH automatically consider the drug to be a hazardous drug and add it to 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. c. What information is redundant, incorrect, missing, or not needed? Relevant information about this document from Regulations.gov provides additional context. The documents posted on this site are XML renditions of published Federal 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. Please provide information about your professional experience, if any, of implementing control strategies for exposures to hazardous drugs in healthcare or similar settings. Genotoxicity has been noted in Chinese hamster ovary cells. 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. 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: Add a new category for drugs that sublime and offer information about proper handling, including the conditions under which sublimation (transition of a solid substance to a gas) happens as well as the need to filter and exhaust the work area where such drugs are used. 2020-N-0145 for ''Reporting Associated With Animal Drug and Animal Generic Drug User Fees.'' Received comments, those filed in a timely manner (see is not clearly outlined with respect to the evaluation process. Document page views are updated periodically throughout the day and are cumulative counts for this document. USP General Chapter <800 . NIOSH response: NIOSH applies the same methodology for evaluating each drug approved by the FDA Center for Drug Evaluation and Research, regardless of class. NIOSH response: BCG, a vaccine approved by the FDA Center for Biologics Evaluation and Research, was included in the original 2004 Alert and `grandfathered' into the List. NIOSH carefully considered all of the peer reviews and public comments and determined that significant, substantial changes should be made to the draft Policy and Procedures, the list of drugs proposed for placement on the List, and also to the organization of the List itself. Of the 275 drugs identified during that timeframe, two had special handling information specified by the manufacturer (MSHI) and were automatically placed on the List. USP 800 only states Table 1. 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. Comment: Olaparib should not be placed on the List because the risk to direct occupational healthcare worker exposure is anticipated to be minimal when handling intact olaparib capsules. The FDA requirements for tested and reported endpoints generally overlap with the NIOSH definition of a hazardous drug. This drug is administered as a coated tablet, self-administered by the patient at home; as such, ivabradine poses no risk to healthcare workers. USP <800> incorporates by reference the NIOSH List and imposes certain requirements on its users when handling certain drugs on the List. 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. Moreover, caution should be taken when making determinations about potentially hazardous drugs because causality is not necessarily demonstrated by a strong association just as absence of causality is not necessarily demonstrated by weak associations; associations that demonstrate a monotonic trend in health outcome frequency (steadily increasing or decreasing without ever changing direction) are not necessarily causal if a confounding factor demonstrates a dose-response relationship with the health outcome; and prior beliefs should not be allowed to cloud judgment with regard to plausibility. Comment: The methodology used to develop the list of drugs proposed for placement on the List was not the same as the methodology used in previous years. Carcinogenicity/genotoxicity: Cited studies in the package insert demonstrated an increased incidence of tumors in hamsters and rats. documents in the last year, 931 . 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. Public comments on the drugs and drug class proposed for placement on the List in 2018 are summarized and answered below. The last paragraph of this section is particularly confusing to the reader. This text is a courtesy copy of General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings, intended to be used as an informational tool and resource only. The only potential risk to healthcare workers is of an accidental needle stick, which would not inject a pharmacologically active dose. Accordingly, the monoclonal antibodies bevacizumab, blintumomab, and trastuzumab should not be placed on the List, and pertuzumab should be removed from Table 1. NIOSH may consider molecular weight along with the other intrinsic molecular properties of a drug that affect the hazard a drug poses. Procedures for deactivating, decontaminating and cleaning. Not refining the List to identify real risks of occupational exposure could lead to overwarning for drugs that present little or no workplace risk. See https://www.cdc.gov/niosh/docs/2016-161/default.html for all drugs with special handling information added to the 2016 List. You can review and change the way we collect information below. on If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. 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. Urofollitropin AHFS Class: Ovulation stimulator. establishing the XML-based Federal Register as an ACFR-sanctioned 05/01/2023, 258 This chapter alone is not sufficient for a comprehensive approach to safe handling of hazardous drugs . 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. . Are the screening and evaluation categorization processes described by the draft policy and procedures scientifically sound? NIOSH response: NIOSH has evaluated each drug individually and not by class of drug. better and aid in comparing the online edition to the print edition. The subsequent description of a site risk Start Printed Page 25441assessment does not seem appropriate here. 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 manufacturers of trabectedin (Yondelis), inotuzumab ozogamicin (Besponsa), polatuzumab vedotin (Polivy), enfortumab vedotin (Padcev), trastuzumab deruxtecan (Enhertu), sacituzumab govitecan (Trodelvy), loncastuximab tesirine (Zynlonta), melphalan flufenamide (Pepaxto), belantamab mafodotin (Blenrep), and tisotumab vedotin-tftv 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. Comment: NIOSH should include the professional qualifications of the NIOSH staff who perform these evaluations. As such, the use of animal studies to evaluate the hazardous nature of a drug should be explicitly stated.. 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 is seeking input from the public on the draft risk management strategies document and table to ensure that they contain accurate and helpful information. 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). on The chapter describes containment requirements only for HD Active Pharmaceutical Ingredients (APIs) and antineoplastic drugs requiring manipulation. Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. 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. Throughout the healthcare landscape, people are asking, "What is USP 800?" Comment: Prior to USP <800>, the NIOSH List was considered a precautionary recommendation. But the USP <800> standards are too restrictive and overreaching, and the chapter's incorporation into state law places facilities at legal risk if they fail to comply. Director,National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. and III.B: bevacizumab, botulinum toxins, darbepoetin alfa, interferon beta-1b, osimertinib, trastuzumab, and triazolam. 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.. A pharmacy's list of hazardous drugs should be reviewed ever 12 months with a document review, when a new agent or dosage form is added, or if storage, preparation, or administration of the hazardous drug will not meet USP <800> standards and an assessment of risk must be done. 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. The President of the United States communicates information on holidays, commemorations, special observances, trade, and policy through Proclamations. On the contrary, if a party submits a written request for reconsideration, NIOSH will be responding in these instances. 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 has determined that exenatide extended-release caused a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats. Because dosage forms can change and new dosage forms may be approved, dosage form is not considered in making List placement determinations. Comment: The draft Policy and Procedures should provide the drug manufacturer with transparent documentation as to the basis of adding a drug to the List. Without a thorough understanding of the basis for adding a drug, the drug manufacturer may not be able to formulate a request for reconsideration of the drug. Comment: Interferon beta-1b should not be placed on the List, or, in the alternative, it should only be placed on Table 3. Accordingly, NIOSH proposes to place dihydroergotamine 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. Reproductive toxicity/teratogenicity: The FDA classifies lapatinib as pregnancy category D indicating positive evidence of human fetal risk. 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. In the February 2018 Request for Comment, NIOSH requested comment on a draft Policy and Procedures for developing the List. Is the threshold of information required to move from the screening process to the full evaluation process clearly described? If emailing please type 508 Accommodation PR#9342 without quotes in the subject line of the email. Manufacturer recommendation: that females of reproduction potential use effective contraception during and for four months after completing therapy. USP General Chapter <800> AHazardous Drugs Handling in Healthcare Settings USP first published General Chapter <800> in February 2016, with the official date anticipated for December 2019. 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.

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