I wrote this article in 2009, as a student, for a rotation project. While it was of course years prior to USP <800>, the information in this article is just as true today as it was then. Because it was written as a student project, the writing style is more academic in nature than I usually write for this website, but I hope you will nonetheless find lots of good information in here you can use in your pharmacy. I made minor edits for clarity and readability.
I decided to post this article because:
1) there are a lot of pharmacies gearing up for USP 800 taking effect, and
2) my article on hazardous drug handling in the community pharmacy has been so popular. This article expands on the information provided in it.
Background
Hazardous drugs pose significant threats to healthcare workers, oftentimes on a daily basis, and substantiate the need for proper education among all involved. Workers may be exposed through transporting, distributing, unpacking, preparing, administering, and disposing of those drugs. Effects on healthcare workers include fetal and reproductive toxicity as well as cancer. Occupational cyclophosphamide exposure, for example, has been estimated to lead to as many as 50 additional cases of cancer each year for every million workers exposed. Moreover, controlled surveys have revealed an increased frequency of complaints of minor ailments, such as chronic coughing, headaches, and dizziness among healthcare workers who handle hazardous drugs at work.
These risks can be reduced by educating workers as well as developing institutional protocols that aim to identify hazardous drugs and limit occupational exposure to them. The aim of this article is to provide an overview of ways in which both the institution as well as the worker can strive to reduce occupational exposure to hazardous drugs. It is important to note that the responsibility lies with both; it is up to the institution to develop sound practices, and it is up to the workers to read and follow carefully the practices set forth by the institution.
Educational Resources
The American Society of Health-Systems Pharmacists (ASHP) publishes and updates guidelines on handling hazardous drugs that are based on the primary literature as well as government reports. This is a great place to begin to gather general information, get a good overview of hazardous drugs in the workplace, and obtain many references. The guidelines are updated occasionally, with the newest guidelines being current to 2004.
[PC]: USP <800> can be downloaded for free here and is currently probably the best place to start, though both the ASHP and NIOSH guides (described below) are excellent as well.
The Material Safety Data Sheet (MSDS) is another great resource specific to a particular drug. It helps the institution assess the level of risk of exposure to the drug in question and gives resources on potential routes of exposure, the acute and chronic health effects due to exposure, proper first aid measures, fire and explosion data, appropriate personal protective equipment (PPE) and handling procedures, and proper spill procedures. The MSDS may be obtained from the manufacturer or distributor of the chemical.
[PC}: The MSDS has been slightly reformatted since I originally wrote this article and is now termed a Safety Data Sheet (SDS). Because of when this article was written, MSDS is used throughout.
The National Institute for Occupational Safety and Health (NIOSH), a division of the Centers for Disease Control, also publishes guidelines on preventing occupational exposure to hazardous drugs in the healthcare setting. These guidelines, including a printable .pdf, are available for free download online. In it, they describe the potential for exposure including routes of exposure, evidence that workers get exposed, and recommendations on everything from handling and packaging to proper selection of ventilation cabinets.
Other publications by NIOSH include guidelines on PPE in the workplace, medical surveillance for healthcare workers exposed to hazardous drugs, and specific guidelines regarding the handling of Micotil 300, an antibiotic used in veterinary medicine with health risks to humans.
The Occupational Safety and Health Administration (OSHA) publishes a technical manual, a hazard communication standard, and an occupational exposure to hazardous chemicals in laboratories standard. Guidelines are also published by the Oncology Nursing Society.
What is a Hazardous Drug?
NIOSH classifies hazardous drugs on several criteria:
Carcinogenecity
Teratogenecity or developmental toxicity
Reproductive toxicity
Organ toxicity at low doses
Genotoxicity
Structure and toxicity profiles of new drugs that mimic existing drugs determined hazardous by the above criteria
ASHP’s classifications parallels those of NIOSH. It is up to the individual institution to develop their specific list of hazardous drugs, taking into account the above factors.
The World Health Organization’s International Agency for Research on Cancer (IARC) also provides a complete list of agents they have reviewed for carcinogenicity.
Their classification is based on the following system:
Class 1 (carcinogenic to humans),
Class 2A (probably carcinogenic to humans)
Class 2B (possibly carcinogenic to humans)
Class 3 (unclassifiable as to its carcinogenicity to humans)
Class 4 (probably not carcinogenic to humans).
It is not exclusive to therapeutic agents, but is nonetheless a great resource to use when assessing carcinogenicity.
The National Toxicology Program, part of the Department of Health and Human Services, publishes the Report on Carcinogenicity (RoC), currently in its 14th edition. The website is a bit more difficult to navigate than the IARC, but would be useful to certain institutions.
Exposure Routes
Drugs may enter the body through inhalation, ingestion, contaminated food products, hand-tomouth, or dermal contact. The route of exposure that is most important is dependent on the drug. For example, a report published in 1992 found no significant dermal absorption of doxorubicin, vincristine, or vinblastine, implying a different route of exposure for those drugs. Because the primary route is different for every drug and oftentimes is unknown, it is prudent to protect workers against all possible routes of exposure.
The most important routes of exposure in the workplace (the way in which most drugs are absorbed) are believed to be inhalation and dermal absorption. Standard sampling methods have generally detected either none or very low levels of drugs in the aerosol and gaseous phase in the pharmacy and clinic environment; however, there is some concern that many of the hazardous drugs are volatile and thus wouldn’t be captured on a standard sampling filter. Thus the idea of inhalational exposure is a topic of current debate and limited evidence.
As far as dermal absorption, numerous studies have confirmed the presence of hazardous drugs on the surface of biological safety cabinets, tables, and counter tops. The ability for contamination to spread to many surfaces in the work area further emphasizes the need for proper institutional standards and training for employees.
Assessing the Workplace and Developing a Comprehensive Safety Plan
Before hazardous drugs are ordered the workplace needs to be assessed to determine if it can properly handle their presence. Employees need to be trained, and policies need to be in place with the proper committees responsible for updating those policies. The culmination of this results in the comprehensive safety plan for the hospital.
The safety plan must be developed with input from all involved, including those involved in transport, preparation, administration, and disposal. The departments involved might include pharmacy, medical staff, nursing, housekeeping, transportation, maintenance, safety, and clinical laboratories.
Developing an institutional list of hazardous drugs
One of the most important steps in the comprehensive safety program involves the creation of a list of hazardous drugs that are used at the institution. Steps must be taken to identify those drugs as soon as they arrive and throughout the life of the drug at the institution, ending with proper disposal. It is also important that this list be updated on a regular basis.
New drugs added to formulary or ordered at the institution should be evaluated using the MSDS provided and other applicable resources for all potential toxicities, as described above.
Institutions must make the MSDS available for all hazardous agents used. Part of the safety program should include a process for updating the database of MSDS’s as new drugs and chemicals are introduced into the workplace.
Environmental assessment
All hazardous drugs, areas where hazardous drugs are going to be handled, and packaging associated with hazardous drugs should be labeled so that it is obvious to all workers of the contents. It is important to make sure that labels are universally understood so that language barriers don’t endanger safety. If workers aren’t aware of the risks they can’t protect themselves from them, so proper labeling is one of the most crucial aspects of the entire program.
Areas where hazardous drugs are prepared or administered should be separated from other areas of the hospital and clearly labeled for staff. For some institutions, this might mean expanding or renovating existing areas to accommodate the new requirements. Additional biological safety cabinets will be needed as well, which requires more space and some thought as to airflow and design of the hospital.
Shelving and carts where hazardous drugs are stored or transported should have a sufficient barrier on them to prevent vials from falling off and breaking. Moreover, hazardous drugs should be stored in a different area than nonhazardous drugs, so additional shelving will be necessary when the decision is made to use hazardous drugs.
Training Programs
Training programs should include everyone with potential for exposure to hazardous drugs, not just the medical staff. Maintenance workers, housekeepers, and volunteers are just some of the staff with the potential for exposure. It is potentially even more crucial that non-medical staff be included because they are less likely than medical staff to be able to recognize hazardous drugs, fully understand the implications of exposure, and know the appropriate steps to take to reduce exposure.
A best practice would be to train all employees of the hospital to some degree. Graded training programs could be developed that included basic training for everyone as well as training for specific tasks such as preparation, administration, cleanup, and disposal. Basic training might include topics such as recognizing labeling, routes of exposure, appropriate PPE, and hospital resources in case of accidental exposure or a spill that needs cleanup.
Appropriate PPE
Gloves: Gloves are essential whenever working with hazardous drugs. As stated above, a major route of exposure is through dermal contact. Workers should be wearing double gloves that are powder free. The powder on gloves tends to concentrate the contamination, making it easier to become exposed or to expose other workers through surface contamination.
The American Society for Testing and Materials (ASTM) has testing standards for determining if glove materials can withstand penetration with chemotherapy agents. Materials that are sufficient include latex, nitrile, and neoprene/polyurethane. Any gloves being used for chemotherapy should meet these testing standards and be designated separately in the hospitals as chemotherapy gloves.
Other practices to reduce exposure include changing gloves every 30 minutes, if contaminated with a spill, or become compromised with a tear or break in the barrier. Workers should inspect gloves before use, wash hands before and after use, and dispose of all PPE in designated bins after use. 70% isopropyl alcohol may be used to sanitize gloves as it has been shown not to degrade the barrier provided by the gloves.
Gowns: Gowns should be worn anytime during preparation, administration, spill control, and waste management. They should be of a non- or low-permeable, lint-free fabric and be disposable. Because washable gowns absorb fluids, they are inappropriate for hazardous drug PPE. In addition, only gowns with a polyethylene or vinyl coating will provide adequate protection against spills with hazardous drugs. Early evidence suggests that gowns might offer protection for two to three hours, but further research is still needed.
Eye and face protection: When there is a possibility of a splash or spill face protection should be worn. It is best to wear face shields rather than goggles because they offer protection of the entire face rather than just the eyes.
Shoe and hair covers: In sterile compounding shoe and hair covers decrease the chance of contamination in the sterile room. However, when compounding with hazardous substances, used shoe and hair covers should be considered contaminated and need to be removed prior to leaving the room. Moreover, since they are contaminated, they should be removed with gloved hands only.
Respirators: Respirators are required anytime there might be a splash or spill outside of the biological safety cabinet. Workers using respirators must be trained and fittested for the respirator as required by the OSHA Respiratory Protection Standard. Surgical masks do not provide appropriate protection and only a NIOSHapproved respirator should be used. The NIOSH N95 respirator provides protection against airborne particles but offers no protection against gases and vapors.
Biological Safety Cabinets (BSCs)
BSCs should be used when preparing hazardous drugs. There are several types of BSCs, but any that are used for hazardous drugs should have a negative airflow design that moves air away from the worker. It is best to consult the manufacturer of the BSC on the various designs so they can help the institution get the right BSCs for their needs. Proper training of the BSC is crucial to its success, and thus training should be part of the safety program.
Decontamination
Deactivation of a hazardous drug is the best method for cleaning a spill. Currently there is no chemical that will deactivate all hazardous drugs, but information about controlling spills may be found in the MSDS. Isopropyl alcohol is not recommended because it will not deactivate most drugs and instead might spread the contamination. A solution of sodium hypochlorite (bleach) is recommended for many drugs and is a reasonable first choice if no information about cleanup is readily available.
Medical Surveillance Programs
NIOSH recommends that institutions develop surveillance programs to monitor employees’ exposure to hazardous drugs. This includes baseline and periodic followup physicals that might include lab tests such as a CBC and UA, questions regarding reproductive and general health, and followup for workers with a significant exposure. In addition, compliance regarding the use of PPE should be evaluated periodically so that the appropriate changes may be made to maximize compliance. If available, the environment may be assessed for surface contamination.
Conclusions
An estimated 5.5 million workers are potentially exposed to hazardous drugs in the workplace. Considering the potential for serious acute and chronic health adverse effects, it is imperative that the proper precautions are taken when the decision is made to use hazardous drugs in the institution.
The precautions are multifactorial, and include proper education and training, planning of the worksite, identification, exposure protection, decontamination, and medical surveillance. The responsibility lies with both the institution and the individual to make the workplace safer for everyone involved.
References
ASHP Council on Professional Affairs. ASHP Guidelines on Handling Hazardous Drugs. Am J HealthSyst Pharm. 2006; 63:117293.
NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. National Institute for Occupational Safety and Health. Accessed online at http://www.cdc.gov/niosh/docs/2004165 on December 12, 2009.
Personal protective equipment for health care workers who work with hazardous drugs. National Institute for Occupational Safety and Health. Accessed online at http://www.cdc.gov/niosh/docs/wpsolutions/2009106 on December 12, 2009.
Medical surveillance for health care workers exposed to hazardous drugs. National Institute for Occupational Safety and Health. Accessed online at http://www.cdc.gov/niosh/docs/wpsolutions/2007117 on December 13, 2009.
Preventing worker deaths and injuries when handling Micotil 300© . National Institute for Occupational Safety and Health. Accessed online at http://www.cdc.gov/niosh/docs/wpsolutions/2007124 on December 13, 2009.
Controlling occupational exposure to hazardous drugs. Occupational Safety and Health Administration. Accessed online at http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html on December 13, 2009.
Hazard communication standard [29 CFR 1910.1200]. Occupational Safety and Health Administration. Accessed online at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=100 99 on December 13, 2009.
Occupational exposure to hazardous chemicals in laboratories standard [29 CFR 1910.1450]. Occupational Safety and Health Administration. Accessed online at http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=101 06 on December 13, 2009.
Material Safety Data Sheet – Estriol. Science Lab.com. Accessed online at www.sciencelab.com/xMSDSEstriol9925870 on December 26, 2009.
IARC monographs on the evaluation of carcinogenic risks to humans. World Health Organization. Accessed online at http://monographs.iarc.fr/ENG/Classification/index.php on December 26, 2009.
The National Toxicology Program. Accessed at http://ntp.niehs.nih.gov/ on December 26, 2009.
Nixon S, Schulmeister L. Safe handling of hazardous drugs: are you protected? Clin J Onc Nurs 2009; 13(4):4339.
Respiratory Control Standards. Occupational Safety and Health Administration. Accessed online at http://www.osha.gov/SLTC/respiratoryprotection/standards.html on December 26, 2009.
Allen LV. Compounding with hazardous drugs. Secundum Artem 2008;15(2). Accessed at http://www.paddocklabs.com/publications.html on December 26, 2009.
Keywords: USP 800, NIOSH, HD, hazardous drug
