by Hank Rahe
Parenteral products are to be terminally sterilized if the product is robust enough to tolerate the sterilization process, per FDA requirements. However, a majority of products currently being given by injection are manufactured using an aseptic process. The use of aseptic processing for these products reduces the sterility assurance level from 10-7 (one in a million) to the range of 10-3 (one in a thousand).
Two elements play a key role in determining the sterility assurance level of aseptically manufactured products. The first element is the quality of the environment, in terms of particle control. The fewer particles in an environment that has been properly sanitized, the less likely that the product will become contaminated. The FDA guideline for products manufactured via aseptic processing requires a Class 100 environment, per Federal Standard 209, with a controlled surrounding background. The background is controlled at either Class 10,000 or Class 1,000. This defines the cleanroom requirements for the majority of manufacturing environments.
In order to maintain the particle control level in cleanrooms, personnel must be gowned to eliminate the particles generated while they work in the environment. As the quality level of the environment increases, so must the level of gowning or protection from particle generation also increase.
The second element is proper sanitizing of surfaces and the materials moving into the aseptic environment. This is critical because it destroys, or reduces, the growth rate of microorganisms that are present in the environment. It is also important that the capabilities of the sanitizing compounds being used are understood. There are differences in the type and range of the organisms that sanitizing products will destroy and in the residual time the product must be in contact with the organism. To prevent the organisms from developing resistance to the compound, sanitizing materials need to be rotated.
The use of barrier/isolators, as a replacement for laminar flow technology in cleanrooms, greatly reduces the dependency on aseptic technique and removes the person, which is the greatest source of contamination, from the product environment. Current data indicate that using barrier/isolation technology, the sterility assurance level of aseptically processed products can be increased by two orders of magnitude.
Further aseptic manipulations of parenteral products can only reduce the sterility assurance level from the baseline established when the products were manufactured. These manipulations take place in the hospital pharmacy and at patient delivery. Generally, the pharmacy IV areas are equipped with laminar flow hoods or Class II biological safety cabinets, which are placed in uncontrolled environments. There may be an unrealistic expectation in the use of aseptic technique for infection control, given the lack of gowning and sanitizing practiced in these environments.
Centers for Disease Control (CDC) statistics have shown a significant increase in nosocomial infections. These are infections that are acquired during a hospital stay. William Jarvis, MD, acting director of the CDC hospital infections program, reports that hospital acquired infections claim 90,000 lives and cost $4.5 billion per year.
Given the recent information concerning contamination that was found outside of Biological Safety Cabinets (see “Contaminants found outside Class II BSCs,” CleanRooms, October 1999, page 1, and “Technique may be culprit behind Class II BSC contamination,” November 1999, page 1) and the potential of reducing the sterility assurance level of parenteral products, it is time that hospitals in the United States follow the lead of the European Community and move into barrier/isolation technology.
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Hank Rahe is director of technology at Contain-Tech in Indianapolis. He is an expert in the areas of conventional and advanced aseptic processing. He is a member of the CleanRooms Editorial Advisory Board.