Hazardous Compounding in Health Systems
Linda F. McElhiney, PharmD, RPh, FIACP, FASHP, FACA
For more than four decades hospitals have been treating their patients with hazardous drugs, including antineoplastic agents, anti-viral medications, hormones, biological modifiers, and immunosuppressive agents. For patients that are suffering from chronic or potentially life-threatening medical conditions, the therapeutic benefits of these medications far outweigh the side effects associated with them. However, studies have shown that healthcare workers who are exposed to these hazardous medications can develop serious adverse events, such as teratogenic effects or cancer.1 The best defense against occupational exposure is proper training, preparation of hazardous medications using the proper environmental and engineering controls, and the use of personal protective equipment (PPE) and devices.
Guidelines and Regulations
What resources are available to aid pharmacy leaders in developing standard procedures within their facility for handling hazardous drugs and protecting their staff? Although several organizations have published guidelines about safely handling hazardous drugs and preventing occupational exposure, there is no single resource available that completely addresses this issue for pharmacy staff. The American Society of Health-System Pharmacists (ASHP) revised their guidelines in 2006 to harmonize with the National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) guidelines. These guidelines may be the best comprehensive resource available for pharmacies that compound and handle hazardous preparations. The current published documents include:
- American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs. Am J Health Syst Pharm 2006; 63(12): 1172-1191.
- National Institute for Occupational Safety and Health. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings. DHHS (NIOSH) Publication No. 2004-165. Washington, DC. [Centers for Disease Control and Prevention Website.] 2004. Available at: www.cdc.gov/niosh/docs/2004-165/. Accessed December 13, 2012.
- National Institute for Occupational Safety and Health. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012. DHHS (NIOSH) Publication No. 2012-15. Washington, DC. [Centers for Disease Control and Prevention Website.] 2012. Available at: www.cdc.gov/niosh/docs/2012-15/. Accessed December 13, 2012.
- Occupational Safety and Health Administration. OSHA Technical Manual. Controlling Occupational Exposure to Hazardous Drugs. Section VI, Chapter 2. [United States Department of Labor. OSHA Website.] Available at: www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html#2. Accessed February 10, 2012.
- Polovich M, ed. Safe Handling of Hazardous Drugs. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2011.
Pharmacy leaders must read the published documents available and create their own standard procedures for their facilities. Unfortunately, this situation can be a problem because interpretation of these documents can vary among the pharmacy leadership, and there is a tendency to "pick and choose" what will and will not be done.
There are official standards in the United States Pharmacopeia (USP) for nonsterile and sterile compounding, but no official chapter with standards that address all aspects of hazardous compounding. USP Chapter <797> for sterile compounding briefly addresses the compounding of sterile hazardous preparations.2
Training and Education
All pharmacy staff that compound hazardous preparations should be formally trained on handling hazardous drugs, just as they do for sterile compounding. Training should include information about PPE, closed-system transfer devices (CSTD), contamination risks, decontamination procedures, negative-pressure compounding environments, waste disposal, transportation, and compounding techniques used to prepare hazardous substances.
There are commercial programs available through professional organizations to aid in training personnel on the proper way to handle hazardous drugs. Commercial kits are also available to help assess the compounders' technique. For the safety of the compounders, all personnel should be assessed annually and pass a written exam about hazardous compounding.
Environmental and Equipment Controls
All hazardous preparations, sterile or nonsterile, must be prepared in a Class II B biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI), also know as a barrier isolator. If the hazardous preparations are sterile, the BSC or CACI must provide an International Organization for Standardization (ISO) Class 5 environment with protective engineering controls. The BSC or CACI should be decontaminated before and after the compounding process and at the end of the day or shift per the manufacturer's instructions to avoid cross contamination.
The BSC or CACI should be located physically in another ISO Class 7 area that provides not less than 0.01-inch water column negative pressure to an adjacent positive-pressure ISO Class 7 anteroom. The BSC and CACI should optimally be 100% vented to the outside are through a HEPA filter; there are BSCs and CACIs that do not require the venting. There are older facilities that do not have ISO Class 7 negative-pressure compounding areas. If the CACI meets the requirements in USP <797>, but is not physically located in an ISO Class 7 buffer area, the compounding area must maintain a minimum negative water pressure of 0.01-inch water column and have a general exhaust system with a minimum of 12 air changes per hour. All hazardous materials should also be stored in this type of environment.
Ideally, there should be a separate BSC or CACI for sterile and nonsterile hazardous compounding; however, not all facilities have the space or resources for two BSCs or CACIs. If sterile and nonsterile hazardous compounding must be done in the same BSC or CACI, it must be decontaminated, cleaned, and disinfected between the nonsterile and sterile hazardous compounding. Note: Do the sterile compounding first to avoid the risk of particulate matter that may be generated from nonsterile compounding procedures.
Personal Protective Equipment and Devices
The personal hand hygiene and gowning procedures are very similar for handling and compounding hazardous substances. Gowns should be waterproof or coated to prevent the hazardous substances from soaking through to the compounder's skin. Gowns should be disposable and immediately discarded after each compounding session.
Gloves must be tested and approved to use for handling chemotherapeutic agents. The gloves are usually made out of nitrile material and must be sterile. The compounder should double glove, and the gloves should be sterile when compounding sterile hazardous preparations. If the outer glove is contaminated during the compounding process, it should be removed before the compounder removes his or her hands from the BSC or CACI to prevent contaminating the environment and equipment outside of the BSC or CACI.
A compounder working with volatile hazardous substances should wear a respirator mask to avoid accidental inhalation exposure. Eye and face shields should be worn if there is a possibility of splashing or uncontrolled aerosolization of the hazardous substance. Disposable hair and shoe covers must be worn in the hazardous compounding area. The covers must be promptly removed as the compounder is leaving the area and properly disposed to avoid contaminating the rest of the pharmacy.
If the hazardous substances are packaged in vials or bags, CSTDs can provide additional protection from exposure for the compounding personnel. A CSTD is a vial-transfer system that allows no venting or exposure of the hazardous substances to the environment. Even though the hazardous substance is contained within the CSTD, all compounding must be done in BSCs and CACIs. USP <797> allows for the use of CSTDs along with the BSC or CACI in facilities that prepare a low volume of hazardous compounds and the BSC or CACI is located in a non-negative room.
Nonsterile Hazardous Compounding
Most people associate cytotoxic drugs with parenteral antineoplastic agents or anti-viral medications, but there are several hazardous medications that are taken orally or applied topically. These agents can be just as or more dangerous than the parenteral cytotoxic agents. A compounder can use the CSTDs to protect against exposure to the parenteral agents; however, there is really no protective device available when working with nonsterile hazardous substances other than PPE and a BSC or CACI or Class II powder containment hood.
If possible, always use disposable equipment when preparing oral liquids or topicals. Disposable, sterile mortars and pestles are commercially available. Even though they are pricey, the compounder does not have to decontaminate and clean them after use, which avoids the risk of contaminating the environment and exposing the staff to hazardous materials. Calibrate the final container to the desired volume to avoid contaminating the pharmacy's graduated cylinders.
If working with small volumes (60 mL or less) when preparing suspensions, use the syringe-to-syringe method to mix the vehicle and the powder together. The powder is backloaded into a Luer-lock syringe, and the liquid vehicle is drawn up in another Luer-lock syringe. The two syringes can be connected with a Luer-lock-to-Luer-lock connector and the contents pushed back and forth between the two syringes until a homogeneous mixture is obtained. The final suspension can be added to the final container and all of the syringes and connector can be discarded in the hazardous waste container with no mess or concerns about decontaminating equipment.
Hazardous tablets that must be split should be done in a BSC, CACI, or Class II powder containment hood and should not be done on countertops in the pharmacy or in the medication rooms on the nursing units. Tablets can crumble and create hazardous particulate matter that can ultimately contaminate the environment. Use dedicated tablet cutters or straight-edge razors to split these tablets. Make sure that the tablets are packaged in manual blister packs or baggies before removing from the hoods.
Hazardous drugs provide tremendous therapeutic benefits for patients with chronic or life-threatening medical conditions. They can cure certain cancers or put them in remission to extend the life of the patient and improve the patient's quality of life. AIDS patients can now live a long, productive life because of the anti-viral agents that have been developed. The success of organ transplants has significantly improved with the new immunosuppressive agents. However, these hazardous drugs can cause serious health problems in healthy healthcare workers. Pharmacy leaders need to ensure that the staff is properly protected from being unnecessarily exposed to these agents by providing proper training, proper environmental equipment and controls, and protective equipment and devices.
Linda F. McElhiney, PharmD, RPh, FIACP, FASHP, FACA
Compounding Pharmacy Operations Coordinator
Indiana University Health
550 N. University Boulevard, AOC 6201
Indianapolis, IN 46202
- Martin S. The adverse health effect of occupational exposure to hazardous drugs. Community Oncol 2005; 2(5): 397-400.
- United States Pharmacopeial Convention, Inc. United States Pharmacopeia 35-National Formulary 30. Rockville, MD: US Pharmacopeial Convention, Inc. 2012.