by Hank Rahe
 |
Initial safety testing of new pharmaceutical compounds cannot, in most cases, generate enough data to determine the “no effect level” in humans. Data concerning the long-term effects of exposure to a drug substance is not available for several years because the data is developed from clinical trial information.
Combined with the fact that smaller amounts of new drug substances will likely cause an effect, as demonstrated by the continued reduction of ethical dose, containment in research and initial development pharmaceutical operations has become a major issue.
Determining the acceptable level of containment and how the containment can be implemented without interfering with the non-routine activities required in the development process has led to changes in the traditional containment approach. The traditional approach has been to rely upon personal protective equipment (PPE).
This approach works until the potency of the compound reaches the microgram range, at which point the decontamination of protective clothing becomes a major issue. Small amounts of residual powder can be easily missed with non-validated cleaning methods and can represent a major exposure problem to the individual wearing the clothing. A greater problem is individuals who may come in contact with the clothing in the cleaning or disposal process because they may be totally unaware of the potentially dangerous material. The saying, “a little bit will not hurt you,” is not true in the case of potent pharmaceuticals.
The cleaning of both equipment and process areas is also a major issue with compounds having low exposure levels. Most areas where these compounds are handled are cleaned by hand, leaving to chance the possibility that small amounts of the compound are present after cleaning. The same problem exists with process equipment in the non-GMP laboratory settings.
To meet these challenges, two approaches have evolved. The first is to develop equipment that can provide validated cleaning methods of PPE, facilities and process equipment. The second is to contain the manipulation of the drug substance at the source.
The development of validated methods for decontamination of PPE has been successful but at a much higher cost than first anticipated. Providing a repeatable method for cleaning protective clothing requires a large version of a dishwasher in which people can be placed as well as the development of a validated cleaning cycle. Both the equipment and the validation are expensive. In some cases, the validated cleaning has involved developing a decontamination cycle using liquids other than water. Individuals in the containment suits during these cycles can be put at some risk if the protective suit leaks.
The techniques used to clean the facility and equipment have also changed. The use of compressed air to “blow off” the equipment is a major problem because it causes the potent powder to become airborne. This technique has been replaced with HEPA vacuuming. The use of large quantities of water with high pressure has been shown to create more contamination problems than it solves.
The containment-at-source approach requires a complete understanding of the activities to be performed within the contained environment and then developing the correct information and translating it to proper ergonomic interactions. Although this may seem common sense, the majority of applications have problems because of the lack of discipline in developing a complete understanding of the functions within the containment environment.
When properly implemented, containment-at-source is usually the more cost-effective approach and offers a higher level of assurance of personnel safety.
Hank Rahe is director of technology at Contain-Tech in Indianapolis. He has over 30 years' experience in the healthcare industry, as well as four years in academia. He is an expert in the areas of conventional and advanced aseptic processing. He is the past chairman of the board of the International Society of Pharmaceutical Engineers, and is a member of the CleanRooms Editorial Advisory Board.