A sampling plan is the cornerstone of successful exposure assessment

by Hank Rahe

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Containment of hazardous drugs requires a total understanding of the drug substance form in terms of solid, liquid, gas or micro aerosol. If the physical form is not considered it will be difficult to measure the potential exposure and, in many cases, will lead to underestimating the potential risk.

One role of industrial hygiene professionals is exposure assessment to provide guidance in developing proper sampling plans and the implementation of these plans. These individuals have been trained in the design of experiments, sampling and interpretation of the sampling results. To develop proper information for assessment of the potential dangers involved in handling of hazardous drugs, we need assurance that the data is correct.

A proper sampling plan establishes the parameters that determine the accuracy and reliability of the study. Capture of the hazardous substance during sampling by a validated method must be demonstrated. Typical capture techniques are air sampling and surface sampling, although these techniques will capture solids and liquids but not gases. In some cases, a partial recovery of micro aerosols can be demonstrated but may require longer periods of sampling time because particles may be extremely small and may not follow settling conventions.

Two examples of surface sampling, which could result in inaccurate data, are:

1.) Surface samples are taken immediately after the clean up of area and the cleaning technique used causes the surface materials to become airborne. This can occur when a high-pressure stream of water is used in the cleaning process. The surface materials are forced to become airborne by the pressure of the water hitting the surface and become suspended in the air. If surfaces are sampled, little or no contaminates will be found. Later sampling of surfaces after the materials have settled will reveal greater contamination levels.

2.) Sampling for gas or micro aerosols using surface sampling in a room, which has a significant number of air changes, will show little or no surface contamination. The gas will not be detected because it will mix with air and will not be captured as a surface contaminate. The micro aerosol is usually made up of very small particles, which will stay airborne for long periods of time and can be influenced by the airflow patterns of the room. The majority of contaminates can be exhausted through the room air handling sources and will not be detected by the surface samples.

In both cases, individuals in the area can experience exposure levels exceeding the level indicated by the surface sampling. Detection of the correct amount of hazardous materials in the breathing zone of workers requires a different sampling technique if the physical form of the materials is gas or micro aerosols.

Interpretation of results is just as critical. Data must be evaluated against a known goal or objective such as the exposure limit of the hazardous compound. In the case of pharmaceuticals, most compounds have an exposure limit set by the manufacturer based on data gathered during the development and testing of the compound. The exposure limit generally includes a safety factor. Some of the characteristics evaluated to determine the safety factor are the effect of the hazardous compound, toxicity and if the effect is reversible. Cytotoxic compounds will typically have a safety factor of one thousand times greater than the no-effect level.

At a recent meeting on containment of potent compounds, an industrial hygienist commented on the question concerning “zero” exposure limits by saying that zero doesn't exist but is sometimes used to explain the inability to measure at very low levels or improper sampling techniques. The majority of compounds, including cytotoxic compounds, have a defined acceptable exposure limit, which can be measured using proper techniques.

Hank Rahe is director of technology at Contain-Tech in Indianapolis. He is the past chairman of the ISPE, and is a member of the CleanRooms Editorial Advisory Board.


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