by Hank Rahe
Proper engineering technology and well-developed procedures are keys to handling potent compounds
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There is increasing concern across the healthcare field regarding the handling of hazardous drugs. The concern is about not only the new and more potent compounds that are being routinely developed by pharmaceutical research, but also a number of compounds that have been in the marketplace for years.
For example, estrogens have created challenges in manufacturing and compounding because they have exposure levels of less than 200 nanograms. At that nanogram exposure level, any open operation involving quantities as small as milligrams can lead to potential over exposure. As the older compounds develop a history, we understand more about the negative effects over exposure can cause. For example, estrogen has recently been declared a carcinogen, adding to the list of serious effects that can result from an over exposure to this compound.
As we understand more about the many forms of cancer, drugs to fight the disease are being introduced at an increasing rate. Also, other uses for cancer-fighting compounds are becoming more common as researchers discover novel forms of delivery for the compounds. One example is coating stents with antineoplastics to prevent blood vessels from regrowing tissue at a point that would close the blood vessel.
Each innovation, while bringing hope and increased life expectancy to all of us, increases the challenges for those involved in developing, manufacturing and delivering these potent compounds. Managing the risk of potential exposures requires that we understand the capability of the contamination-control technologies and implement the proper technology for containment of these compounds, at all potential exposure points.
The potential for contamination includes not only the individuals directly in contact with the compound, but also the casual contact in public places from individuals who were not properly protected in the workplace. For compounds having exposure levels in the low microgram range, enough of the compound to exceed these exposure levels can easily be carried on hands, clothing or personal items commonly present in the production areas if proper engineering controls and procedures are not in place in the workplace.
Facilities must be capable of handling potent compounds, from discovery to final delivery of the patient dosage, by developing and implementing proper engineering controls in the work place. Without proper containment, potent compounds are spread to fellow workers and beyond.
The engineering technologies developed for containing the risk from powders, liquids and gasses fall into three categories:
- Exhausting the air from the area that reduces the airborne concentration by introducing air that is free of the contamination.
- Directionalized airflow that takes the hazardous compound away from the breathing zone of the individual working with the compound.
- Closed systems that separate the hazardous material from the individual by a physical barrier.
Each of these technologies has a band of control that can be expressed in terms of the airborne concentration of the contamination in the area.
Airborne concentrations are measured by using industrial hygiene sampling techniques that collect air in the breathing zone of individuals working in the area and from the surfaces with which personnel can come into contact.
The sample quantity collected is then measured against the defined level of the hazardous material to which individuals can safely be exposed without an adverse effect. Most pharmaceutical companies that develop and market the drugs have preset exposure limits for their products and use these standards to monitor the workplace where the drugs are manufactured.
Collection, measurement and analysis of hazardous compounds requires a well-designed study that describes the techniques to capture the drug in whatever form–liquid, solid or vapor. Industrial hygiene professionals are trained in these techniques and should be involved in the measurement and establishing of work practices.
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Important in the selection of a given technology is the understanding of the workplace in which the technology will be applied and the policies and procedures necessary to support the successful implementation of the technology. For example, the containment of hazardous drugs in the pharmaceutical manufacturing area may be different than a laboratory, hospital pharmacy or patient administration.
Differences that should be considered are the quantity, form of the hazardous drug and the operation taking place in the area where the hazardous drug is being handled. The ability of the drug to become airborne is an important factor to consider and individual activities should be evaluated.
In the manufacturing setting, operations with the concentrated drug substance such as incoming sampling, dispensing and any operation where the drug is directly exposed to the breathing zone of the operator, present the highest risk.
The pharmacies where parenteral antineoplastics are prepared require both ISO Class 5 environment and containment. The typical preparation uses a syringe to extract the drug from a vial and place it into the final patient delivery device, be it a piggyback or syringe. In many cases, a combination of drugs is prepared.
The withdrawal using a syringe and injecting into a piggyback creates pressure on the liquid and causes the drug to aerosol. Quantities in the microgram range have been measured in the area adjacent to this operation. A study showed that proper technique reduced the amount of materials aerosolized, but not to the extent of reducing the airborne concentration below the exposure limit of many of the drugs in this class of compounds.
Patient administration in the hospital, clinic and home creates exposures to the caregiver as well as other individuals that may be in the area of administration. The major exposures occur when the IV set are primed and at the break after administration has been completed. Testing has shown that the site administration levels with primed sets are below exposure levels, if fewer than ten hook ups are prepared per individual per day. The major issue in the administration area seems to be the surface build-up of the hazardous drugs. This is an area where procedures and spill control would be beneficial.
Proper procedures and protocols must be developed and followed, along with a monitoring program that provides a history of the employee's physical well being to support a complete program for safe handling of hazardous drugs.
Hank Rahe is director of technology for Containment Technologies Group and is a member of the CleanRooms Editorial Advisory Board.