Where would you find warnings and special handling for hazardous drugs?
The Occupational Safety and Health Administration (OSHA) first published guidelines for the management of cytotoxic (antineoplastic) drugs in the work place in 1986 (OSHA, 1986), and the guidelines were made available in the peer-reviewed literature that same year (Yodaiken, 1986). OSHA updated the guidelines in 1995 and subsequently posted them to OSHA's website in 1999 (OSHA, 1995; OSHA, 1999). Since OSHA last updated the guidelines, governmental and professional organizations have contributed substantial quantities of scientific investigation results, "best-practices", and policy recommendations, which broadened the evidence base underlying the current practices for safe hazardous drug (HD) handling. NIOSH and the American Society of Hospital Pharmacists (ASHP) (ASHP, 1990) redefined the term "hazardous drug" beyond directly cytotoxic drugs to include additional agents that exhibit specific characteristics in human and animal toxicity [See sec. II.A., Figure 1]. The World Health Organization (WHO) estimates that the number of cancer patients will almost double in the next two decades (WHO, 2014), and the number of healthcare workers (HCWs) needed to care for those patients will grow commensurately. The National Institute for Occupational Safety and Health (NIOSH) estimates that somewhere around 8 million HCWs are potentially exposed (NIOSH, 2009). Show This informational guidance document outlines OSHA's current recommendations for addressing the health and safety hazards faced by healthcare workers who handle HDs, and the background evidence underlying those recommendations. Although work practices and safe HD handling practices have improved in the years since OSHA first published guidance on the subject in 1986 (OSHA, 1986), workplace exposure to HDs remains a problem (Valanis, 1992; Connor, 1999; Connor, 2010). Several recent publications have documented the ongoing failure of employers to adopt, or consistently use, recommended safety practices for handling HDs (Boiano, 2014; Polovich and Martin, 2011). This failure, in conjunction with many information requests from the public on how to safely handle HDs, and the growing population of HCWs with potential HD exposure in their work prompted OSHA to review and revise its recommendations for hazardous drug handling. Most agents that are considered HDs are covered under the Hazard Communication Standard (HCS)[29 CFR 1910.1200], which has undergone a significant update since OSHA's 1995 hazardous drug guidance was issued (OSHA, 2012b). Note that the requirements of the HCS are superseded by those of OSHA's Laboratory Standard, 29 CFR 1910.1450, when an employer is engaged in the "laboratory use of hazardous chemicals" (i.e., use of relatively small quantities of hazardous chemicals on a non-production basis), but this document focuses on the HCS requirements that apply to most healthcare employers. These recommendations apply to all healthcare settings where employees are occupationally exposed to HDs, such as hospitals, physicians' offices, and home healthcare agencies. Because many of the same drugs used to treat humans are also used to treat animals, this guidance is applicable to veterinary practices as well. Sections dealing with work areas and prevention of employee exposure to HDs at a workplace refer to workplaces where pharmaceuticals are used in concentrations appropriate for patient therapy. In settings where employees work with drugs in a more potentially hazardous form (e.g., a more concentrated form encountered in certain components of pharmaceutical manufacturing), measures that afford employees a greater degree of protection from exposure are commonly employed and should be used. Many manufacturers have internal occupational exposure limits, but those limits are not generally available to regulatory agencies; workers may inquire about those limits from the manufacturers separately from the information available in this document. This review will:
Anesthetic agents are not considered in this review, even though exposure to some of these agents is a well-recognized health hazard (NIOSH, 2007). A separate OSHA document on this topic is available at: https://www.osha.gov/waste-anesthetic-gases/workplace-exposures-guidelines (OSHA, 2000). II. CATEGORIZATION OF DRUGS AS HAZARDOUS
III. BACKGROUND: HAZARDOUS DRUGS AS OCCUPATIONAL RISKSIn the thirty years since the publication of OSHA's technical guidance on HD safe handling, the scientific literature on this topic has grown tremendously. In the years since the 2004 NIOSH Alert was issued, over 400 papers on HDs have been published in the peer-reviewed literature. These reports document how vial contamination, preparation, administration, disposal, and other HD handling activities may expose pharmacists, nurses, physicians, and other HCWs to potentially significant workplace levels of these chemicals. It is difficult to set safe levels of exposure to HDs on the basis of current scientific information because the degree of absorption that takes place during work, and the significance of early biological effects on each individual, are difficult to assess and may vary depending on the HD. However, several lines of evidence support the toxic potential of these drugs if handled improperly. In addition, most HCWs are exposed to multiple agents during any work shift, yielding a "mixed exposure" scenario. Therefore, it is essential to minimize exposure to all HDs. Summary tables of much of the data presented below can be found in the scientific literature (Sorsa, 1985; Rogers, 1987; Connor and McDiarmid, 2006).
IV. WORK AREASRisks to personnel working with HDs are a function of the drugs' inherent toxicity and the extent of exposure. Early speculation noted inhalation was the primary route of exposure. However, with the advent of more sensitive drug assays, surface wipe sampling of a number of "marker" HDs has provided a method of examining work areas for HD residue (Sessink, 1992a & b; Sessink, 1997; Kopp, 2013; Fransman, 2005; Fransman, 2007). Numerous studies have shown that surfaces in areas where HDs are stored, mixed, administered, and wasted, as well as where patients are cared for, are contaminated with measurable levels of HD residue (Connor, 1999; Connor 2002; Acampora, 2005; Connor, 2010; Hon, 2013). Studies have detected the presence of HDs in the urine of HCWs who have handled these drugs, and in others who did not work directly with the drugs but who were only in the work area (Sessink, 1997; Wick, 2003; Fransman, 2004; Suspiro, 2011; Hon, 2015). Current belief is that dermal absorption of HD residue from contaminated surfaces is the primary route of exposure for at least some agents, such as cyclophosphamide (Kromhout, 2000; Fransman, 2004; Fransman, 2005). Inhalation, especially of drugs that vaporize, is an additional exposure route, and at least one study of automatic dispensing machines of oral tablets indicates that these devices may generate dust of active pharmaceutical ingredients (APIs) during the counting and dispensing process (Fent, 2014). Exposure is also likely to result from ingestion of contaminated food or drink or through mouth contact with contaminated hands or cigarettes. Accidental injection from the use of needles or contact with broken glass fragments is also of concern. Opportunity for exposure to HDs may occur at many points in the process of handling these drugs. NIOSH has included pharmacy and nursing personnel, physicians, operating room personnel, environmental services workers, workers in research laboratories, veterinary care workers, and shipping and receiving personnel in the workers who handle HDs (NIOSH, 2004). The US Pharmacopeial Convention (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed and consumed worldwide. USP's drug standards are enforceable in the United States by the Food and Drug Administration. USP chapter 797 ("Pharmaceutical Compounding—Sterile Preparations"), notes that when compounding sterile preparations of HDs, they should be handled with caution at all times during receiving distribution, stocking, inventorying, preparation, and disposal (USP 797, 2012). USP's general chapter 800 ("Hazardous Drugs—Handling in Healthcare Settings" published 2/1/2016 in USP 39-NF 34, First Supplement) cautions that both clinical and nonclinical personnel may be exposed to HDs when they create or use aerosols, generate dust, clean up spills, or touch contaminated surfaces during the receipt, preparation, administration, cleaning, or disposal of HDs (USP 800, 2016). NIOSH, ASHP, and others have reported on studies that found drug residue on the outside of HD vials when they arrive at the workplace from the manufacturer or distributor (NIOSH, 2004; ASHP, 2006; Power, 2014). Packing cartons have also been identified as sources of measurable HD contamination (Kiffmeyer, 2000).
V. PREVENTION OF EMPLOYEE EXPOSURE
VI. MEDICAL SCREENING AND SURVEILLANCELike workers who are potentially exposed to other chemical hazards in healthcare, such as ethylene oxide and formaldehyde, those exposed to HDs, which include agents known to be human carcinogens, as well as those which are reproductive and developmentally toxic, should be monitored in a medical surveillance program (ASHP, 1990; ASHP, 2006; OSHA, 1995; ISOPP, 2007; Polovich, 2011; NIOSH, 2013). Medical screening and surveillance is one part of a comprehensive approach for minimizing hazardous exposures, which also includes training, engineering and work practice controls, and use of PPE. The purpose of screening is to identify the earliest reversible biologic effects so that exposure can be reduced or eliminated before the employee sustains irreversible harm. The occurrence of exposure-related disease or other adverse health effects should prompt immediate reevaluation of primary preventive measures (e.g., engineering controls, work practices, and use of PPE). Separately, OSHA views surveillance as the formal evaluation of groups of workers; in this manner, medical surveillance acts as a check on the efficiency and appropriateness of controls already in use (OSHA, 2015). For detection and control of work related health effects, screening is typically performed at specific intervals:
In addition to review of individual worker results obtained during a screening, the data obtained should be analyzed in a systematic fashion to allow early detection of disease patterns in groups of workers. Such surveillance requires systematic collection of information and, usually, some form of electronic data management system, ideally with exposure tracking.
VII. HAZARD COMMUNICATIONThis paragraph is for informational purposes only and is not a substitute for the requirements of the Hazard Communication Standard (HCS) [29 CFR 1910.1200] (OSHA, 2012b). Note that the requirements of the HCS are superseded by those of OSHA's Laboratory Standard, 29 CFR 1910.1450, when an employer is engaged in the "laboratory use of hazardous chemicals" (i.e., use of relatively small quantities of hazardous chemicals on a non-production basis), but this document focuses on the HCS requirements that apply to most healthcare employers.
VIII. TRAINING AND INFORMATION DISSEMINATION
IX. RECORDKEEPINGEmployee exposure records, including workplace monitoring, biological monitoring, and SDSs, as well as employee medical records related to drugs posing a health hazard, must be maintained and access to them provided to employees in accordance with 29 CFR 1910.1020 (OSHA, 2011a). That is, records created in connection with HD handling shall be kept, transferred, and made available for at least 30 years, and medical records shall be kept for the duration of employment plus 30 years. In addition, the HCS does not require training documentation, but sound practice dictates that training records should be created, and include the following information:
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[http://labeling.pfizer.com/showlabeling.aspx?id=490#section-11.3]. Yodaiken RE and Bennett D. OSHA work practice guidelines for personnel dealing with cytotoxic [antineoplastic] drugs. Am J Hospit Pharm 1986;43:1193-204 Zock MD, Soefje S, Rickabaugh K. Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activities using two closed-system products. J Oncol Pharm Pract. 2011;17:49-5 GLOSSARYActive pharmaceutical ingredient (API) - Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity or other direct effect in the diagnosis, cure, mitigation treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. Alternative Duty - Performance of other tasks that does not include the direct handling of HDs. Ante Area - Transition area between the general area and the segregated area containing the CPEC. Hand-hygiene, garbing, staging of components, order entry and other particle-generating activities are performed in the ante area. For sterile compounding, the ante area should meet ISO 7 characteristics and also provides assurance that pressure relationships between rooms are constantly maintained (USP 797, 2012; USP 800, 2016). Batch - More than one unit of a compounded preparation that is intended to have uniform character and quality within specified limits, prepared in a single process, and completed during the same and limited time period. Beyond-use date - The date or time after which a compounded preparation should not be stored or transported. See Pharmaceutical Compounding - Non-sterile Preparations USP <795> and Pharmaceutical Compounding - Sterile Preparations USP <797> for additional details. Biohazard - A biological agent, such as a virus or a condition that constitutes a threat to humans. Biological Safety Cabinet (BSC) - A ventilated cabinet for CSPs, personnel, product, preparation, and environmental protection having an open front with inward airflow for personnel protection, downward high efficiency particulate air (HEPA) filtered laminar airflow for product and preparation protection, and HEPA filtered exhausted air appropriately removed by properly designed building ventilation for environmental protection. Buffer Area - Part of the compounding area where the primary containment engineering control (CPEC) is physically located. Activities that occur in this area are limited to the preparation and staging of components and supplies used when compounding HDs. Chemotherapy glove - A medical glove that meets the American Society for Testing and Materials (ASTM) Standard Practice (D6978-05(2013)) for Assessment of Resistance of Medical Gloves to Permeation by Chemotherapy Drugs. Cleanroom - A room in which the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. Microorganisms in the environment are monitored so that a microbial level for air, surface, and personnel are not exceeded for a specified cleanliness class (See USP 36, Chapter <1116>, "Microbiological Control and Monitoring of Aseptic Processing Environments," and also the definition of "Buffer Area"). Cleaning - The removal of soil (e.g., organic and inorganic material) from objects and surfaces normally accomplished manually or mechanically using water with detergents or enzymatic products. Closed system transfer device (CSTD) - A drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapors concentrations outside the system. Compounded Preparation - A sterile or non-sterile drug or nutrient preparation that is compounded in a licensed pharmacy or other healthcare-related facility pursuant to the order of a licensed prescriber. Compounding personnel - Individuals who participate in the compounding process who are competent and knowledgeable, and responsible for the preparation of HDs, using information from Chapter <797> and <800>, the entity's SOPs, and instructions from the compounding supervisor. Compounding supervisor - The individual who is responsible for developing and implementing appropriate procedures, overseeing facility compliance with Chapter <797> and <800> and other applicable laws, regulations, and standards, ensuring competency of personnel, and assuring environmental control of the compounding areas. Compounding Aseptic Containment Isolator (CACI) - A compounding aseptic isolator (CAI) designed to provide worker protection from exposure to undesirable levels of airborne drugs throughout the compounding and material transfer processes and to provide an aseptic environment for compounding sterile preparations (See USP 797, 2012). Air exchanged from the surrounding environment should not occur unless it is first passed through a microbially retentive filter (HEPA minimum) system capable of containing airborne concentrations of the physical size and state of the drug being compounded. Exhaust air from the isolator should be appropriately removed by properly designed building ventilation. Compounding Aseptic Isolator (CAI) - A primary engineering control designed for use for non-HDs. A laminar airflow workbench (LAFW) or compounding aseptic isolator (CAI) should not be used for the compounding of an antineoplastic HD (USP 800, 2016). Containment Primary Engineering Control (C-PEC) - A ventilated cabinet, designed to establish primary containment and to minimize worker exposures by controlling emissions of airborne contaminants through the following techniques:
A C-PEC may be further defined by its task or use and have other characteristics such as providing ISO 5 air quality in an engineering control used for sterile compounding. Such devices for use with HDs include, but may not be limited to, Class I BSCs (for non-sterile agents only), Class II BSCs, and compounding aseptic containment isolators (CACIs). C-PECs used for sterile compounding should have ISO 5 air quality. C-PECs used for non-sterile compounding do not need to have ISO 5 air quality. Containment Secondary Engineering Controls - The design and operation of the room in which the C-PEC is placed. Restricted access, barriers, special construction technique, ventilation and room pressurization are components of the secondary control strategy. Containment Segregated Compounding Area (CSCA) - A segregated room that is restricted to preparing low-risk HD CSPs with a 12-hour or less BUD or a segregated room that is restricted to preparing non-sterile HDs. Such area should contain a Containment Primary Engineering Control that meets the specifications of USP <797>. Containment Supplemental Engineering Control - Adjunct controls used in concurrence with Primary and Secondary Control Strategies. Supplemental controls offer additional levels of protection and may facilitate enhanced occupational protection as the HD is handled outside of the protective controls of primary and secondary control environments. Containment Ventilated Enclosure (CVE) - A C-PEC used for manipulation of non-sterile HDs. Controlled Environment Testing Association (CETA). CETA, the Controlled Environment Testing Association, is a non-profit trade association devoted to promoting and developing quality assurance within the controlled environment testing industry. http://cetainternational.org/. Deactivation - Treatment of a hazardous drug with another chemical, heat, ultraviolet lights, or other agent to create a less hazardous agent. Decontamination - Inactivation, neutralization, or removal of HDs, usually by chemical means. Disinfectant - A chemical agent that destroys or inhibits the growth of microorganisms that cause disease. Engineering Control - Primary, secondary, and supplemental devices designed to eliminate or reduce worker exposure to a chemical, biological, radiological, ergonomic, or physical hazard. Examples include laboratory fume hoods, retracting syringe needles, sound-dampening materials to reduce noise levels, safety interlocks, and radiation shielding. Entity - A pharmacy, hospital, physician office, clinic, veterinary office, or other location wherever HDs are procured, stored, prepared, dispensed, and distributed to a final user or healthcare personnel who will administer the HD. Expiration date/expiry date -The expiration date identifies the time during which the article may be expected to meet the requirements of the compendia monograph, provided it is kept under the prescribed storage conditions (See USP 34, Labeling in General Notices and Requirements, Section 10.40.100). Globally Harmonized System of Classification and Labeling of Chemicals (GHS) - A system for standardizing and harmonizing the classification and labeling of chemicals. Goggles - Tight-fitting eye protection that completely cover the eyes, eye sockets and the facial area immediately surrounding the eyes and provide protection from impact, dust, and splashes. Some goggles will fit over corrective lenses. Hazard Communication Standard (HCS) - A U.S. government regulation designed to ensure that the hazards of all chemicals produced or imported are classified, and that information concerning the classified hazards is transmitted to employers and employees [29 CFR 1910.1200(a)(1)]. Hazardous Drug (HD) - Any drug identified by at least one of the following six criteria:
Laminar Air Flow Workbench (LAFW) - A primary engineering control designed for use for compounding non-HDs. A laminar airflow workbench (LAFW) or compounding aseptic isolator (CAI) should not be used for the compounding of an antineoplastic HD (USP 800, 2016). Labeling - A term that designates all labels and other written, printed, or graphic matter on an immediate container of an article or preparation or on, or in, any package or wrapper in which it is enclosed, except any outer shipping container. The term "label" designates that part of the labeling on the immediate container [See General Notices and Requirements, 21 U.S.C. 321 (k) and (m)]. Negative Pressure Room - A room that is at a lower pressure than the adjacent spaces and, therefore, the net flow of air is into the room. Personal protective equipment (PPE) - Items such as gloves, gowns, respirators, goggles, face shields, and others that protect individual workers from hazardous physical or chemical exposures. Pharmaceutical product - A commercially manufactured drug or nutrient that has been evaluated for safety and efficacy by the FDA. Products are accompanied by full prescribing information, which is commonly known as the FDA approved manufacturer's labeling or product package insert. Positive Pressure Room - A room that is at a higher pressure than the adjacent spaces and, therefore, the net flow of air is out of the room. Safety Data Sheet (SDS) - An informational document that provides written or printed material concerning a hazardous chemical that is prepared in accordance with the HCS (previously known as a Material Safety Data Sheet (MSDS)). Spill Kit - A container of supplies, warning signage, and related materials used to contain the spill of a HD. Sterilization - A process that destroys or eliminates all forms of microbial life (including spores) and is carried out in healthcare facilities by physical or chemical methods. 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Controlled Environment Testing Association. CETA application guide for the use of surface decontaminants in biosafety cabinets CAG-004-2007. January 7, 2007. http://www.cetainternational.org/reference/CAG0042007i.pdf. Accessed December 16, 2014 Controlled Environment Testing Association. CETA servicing hazardous drug compounding primary engineering controls, CAG-005-2007. 2007. http://www.cetainternational.org/reference//CAG005-v15.pdf. Controlled Environment Testing Association. CETA compounding isolator testing guide, CAG-002-2006. December 8, 2008. Available from CETA website: http://www.cetainternational.org/reference/CETACompoundingIsolatorTestingGuide2006.pdf. Accessed December 16, 2014. Centers for Disease Control Centers for Disease Control and Prevention. Biosafety in microbiological and biomedical laboratories (BMBL) 5th edition. Department of Health and Human Services. December 2009. Centers for Disease Control and Prevention. Hand hygiene in healthcare settings. 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[DHHS (NIOSH) Publication No. 2007-124]. Department of Health and Human Services. 2007. Personal Protective Equipment for Health Care Workers Who Work with HDs. [DHHS (NIOSH) Publication No. 2009-106]. Department of Health and Human Services. 2008. Workplace solutions: personal protective equipment for health care workers who work with hazardous drugs. [DHHS (NIOSH) Publication No. 2009-106]. Department of Health and Human Services. October 2008. Evaluation of Exposures to Healthcare Personnel from Cisplatin during a Mock Interperitoneal Operation. University Medical Center. Las Vegas, Nevada. March 2010. Safe Handling of Hazardous Drugs for Veterinary Healthcare Workers. [DHHS (NIOSH) Publication No. 2010-150]. Department of Health and Human Services. June 2010. Chemotherapy drug evaluation at a medical laboratory - Pennsylvania. September 2011. Multiple Sclerosis Cluster Evaluation in an Inpatient Oncology Ward - Wisconsin. October 2011. Exposures to pharmaceutical dust at a mail order pharmacy - Illinois. December 2011. Chemotherapy drug evaluation at a veterinary teaching hospital - Michigan. April 2012. Chemotherapy drug exposures at an oncology clinic - Florida. June 2012. Medical Surveillance for Healthcare Workers Exposed to Hazardous Drugs. [DHHS (NIOSH) Publication No. 2013-103]. Department of Health and Human Services. November 2012. Workplace solutions: medical surveillance for healthcare workers exposed to hazardous drugs. [DHHS (NIOSH) Publication No. 2013-103]. Department of Health and Human Services. November 2012. Evaluation of Pharmaceutical Dust Exposures at an Outpatient Pharmacy. [DHHS (NIOSH) Report No. 2010-0078-3177]. April 2013. Evaluation of safety climate, health concerns, and pharmaceutical dust exposures at a mail order pharmacy. [DHHS (NIOSH) Report No. 2012-0044-3199]. Department of Health and Human Services. December 2013. Evaluation of Chemotherapy Drug Exposure in an Outpatient Infusion Center. [DHHS (NIOSH) Report No. 2013-0019-3205]. March 2014. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings. [DHHS (NIOSH) Publication No. 2014-138]. Department of Health and Human Services. September 5, 2014. The National Personal Protective Technology Laboratory (NPPTL). Respirator trusted-source information. Section 3: ancillary respirator information. Department of Health and Human Services. September 9, 2014. National Sanitation Foundation (NSF) National Sanitation Foundation. NSF/ANSI 49-2011. Biosafety cabinetry: design, construction, performance, and field certification. Annex E. 2011. Occupational Safety and Health Administration (OSHA) OSHA Summary Publication on Personal Protective Equipment. 2004. OSHA, The Joint Commission, and NIOSH joint letter to hospitals, dated 4 April 2011, on hazardous drugs. Where would you find warnings and special handling for hazardous drugs CVS?Where would you find warnings and special handling for Hazardous Drugs? On the manufacture's Safety Data Sheet.
Which section of USP is the guidelines for the handling of hazardous medications?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.
WHO publishes the official list of hazardous drugs?U.S. Department of Health and Human Services (DHHS), National Institute of Occupational Health and Safety (NIOSH) Publication No. 2004-165, (September 2004). Provides an annually updated list of drugs considered hazardous. NIOSH Warns: Nitrous Oxide Continues to Threaten Health Care Workers.
What will you likely find in a hazardous drug spill kit?Contents of a Spill Kit
Gloves, Disposable bags, Absorbent pads, and. Absorbent socks.
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