Isolation Technology in Biotechnology

During the past several years, isolator technology has begun to gain acceptance as an alternative to using conventional cleanrooms for aseptic processing and sterility testing. Compelling reasons for the current interest in isolator technology include both cost savings and performance. Although isolator systems have not been widely used in the biopharmaceutical industry, they could provide a viable alternative to the construction of cleanrooms where controlled environments are required.

Potential applications for isolator technology in biopharmaceutical manufacturing are as follows:

Cell culture - Maintenance of cell culture banks and initial steps of seed culture expansion are both excellent candidates for the use of isolator technology. Isolator systems can also be used for fermentation operations carried out at working volumes of only a few liters.

Purification - Purification equipment such as chromatography columns and ultrafilters can be located within an isolator. For larger-scale systems it is possible to obtain isolators that enclose a volume of several hundred cubic feet.

Filling of sterile bulk is often the first step in a process in which a manufacturer makes the claim of sterility for a product. At this point, a bulk sterility test is conducted. In virtually all operations, this step is conducted by gowned employees in a Class 100 cabinet or enclosure. If filling of a product into final dosage forms is done on-site, the product can be transferred to a formulation area within a transfer isolator. Constant electrical power is not required because isolators have HEPA filters on both the air supply and exhaust. Thus, isolation is maintained without operation of air blowers.

Compounding - Compounding or formulation is often done under Class 10,000 conditions. In many cases a product is held under clean, but not aseptic, conditions until final filtration. Given proper care and attention to detail in a conventional clean area, this can be done in a manner that minimizes the likelihood of microbial growth in a product. The use of isolation technology makes compounding much safer and allows samples to be taken with complete protection from human-borne contamination.

Aseptic filling into the product delivery systems - Aseptic processing of unpreserved biologicals is an inherently risky operation. Isolators have been used in Europe for aseptic processing for several years. Validation studies have indicated that these systems are capable of attaining contamination rates of zero over several years. There is currently great interest in isolator technology for aseptic filling both among pharmaceutical companies and regulatory agencies.