Endotoxin testing of medical devices with LAL: FDA requirements.
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Biomedical subjects
Publications and source records attributed to C W Bruch.
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Studies of microbial survival in simulated deep-space conditions have established that these conditions will not sterilize contaminated spacecraft. Likewise, data presented at this and previous meetings of COSPAR have shown that many terrestrial microbes, particularly anaerobic sporeformers, readily tolerate simulated Martian environments. Any spacecraft landing on Mars must have a low probability of harboring any terrestrial organisms, especially sporeformers, if the goals of exobiology are not to be compromised. Before the planning, production and monitoring of sterile spacecraft can be undertaken, the theory and principles of sterilization and their application to the special problem of spacecraft sterilization must be understood. The response of a given population of microorganisms to sterilizing agents is affected by several factors; these factors in turn regulate the kinetics of the killing process. The only processes that achieve both surface and interior sterilization are heat and radiation. Of these, dry heat is the agent of choice. If all parts of the spacecraft are assembled under the most rigorous conditions of cleanliness, the capsule can be brought to terminal sterilization containing a total of not more than 10(5) viable organisms. These can be killed by exposure to 135 degrees for 24 hours with a confidence of greater than 10(4). Spacecraft must be specifically designed to withstand such heat sterilization without reduction of reliability. The number of labile parts must be kept to a minimum, sterilized by methods other than heat, and inserted into the sterilized spacecraft by sterile techniques. The entire process must be under very tight control with tests and records of every detail. The sterilized spacecraft must be encapsulated and remain therein during final testing and launch until the capsule is opened in deep space. The design and production engineer must understand how all these procedures will affect the spacecraft, and the biologist must constantly monitor and educate the engineers on the scope and limitations of these various sterilizing procedures.
There is a surprising lack of quantitative data on sterilization by dry heat so that microbiologists have little knowledge of the role played by various biological and physical factors in this sterilizing process. A recent investigation by the author has shown that the aerobic mesophilic bacterial sporeformers, such as Bacillus subtilis and Bacillus coagulans, are the most resistant among several species of sporeforming bacteria to dry heat sterilization. The type of carrier on which the spores are exposed to dry heat markedly affects their thermal resistance. An analysis of four carriers showed that spores on sand or vermiculite are more difficult to destroy than spores on paper or glass. Spores under low vacuums are more susceptible to dry heat sterilization than spores in helium, which are more susceptible than spores in air. Spores trapped in solids have thermal resistance levels two or three times greater than those found for spores exposed to dry heat in air. Preliminary results on the combination of dry heat and ionizing radiation sterilization indicate no synergistic effects, i.e., the destruction obtained with each agent is additive. Another important variable that governs the interpretation of the effectiveness of dry heat sterilization tests is the recovery medium for heat-damaged spores. The kinetics of dry heat sterilization cannot be fully interpreted from the available data. Death follows a logarithmic pattern thereby implying a monomolecular reaction. The mechanism of death is thought to be due to an oxidative process.
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