WOBURN, MA – Advances in isolation technology put conventional, manned cleanrooms on the endangered species list, claims James Agalloco, president of Agalloco Associates, a Belle Mead, NJ, company providing technical services to the pharmaceutical and biotechnology industries.
Agalloco concludes that sterilization of environment is a distinct advantage of isolator systems relative to barrier systems. Microbial monitoring is a necessary part of routine process control. He says isolators potentially offer significant advantages over barrier systems and conventional manned cleanrooms because barrier systems cannot exclude contamination as well as isolator systems.
However, isolation technology is still evolving in the industry – and although they are better than manned aseptic processing, including barrier systems, isolator systems still are not perfect.
“Therefore, the current manned cleanroom is not yet extinct – but it surely should be considered an endangered species,” Agalloco says.
At the June meeting of the Northern New England Chapter of the Institute of Environmental Sciences and Technology (IEST) in Woburn, MA, Agalloco addressed about 30 people from the pharmaceutical and biotech industries, explaining where isolation technology is headed and defining the differences between barrier and isolation technologies.
He told the group that definitions of terms is extremely important because barrier technology and isolation technology are not equivalent.
“All these definitions are a problem when you're trying to read articles about isolation or barrier technologies – how are the terms being used?” Agalloco says. He prefers the term “isolator” to mean a piece of equipment that provides for complete separation between one environment and another, and uses the term “barrier” to mean a material object that separates or serves as a barricade.
Isolation technology includes open and closed systems. Closed systems can sometimes use a barrier system that allows the exchange of air or contaminant during use with an adjacent environment. Agalloco says isolation technology defines isolation as the use of an isolator where the goal is to keep the interior free of contamination. Containment is where an isolator is used to restrict the contamination of the interior.
What we have today, Agalloco claims, is a situation where regulatory concerns usually override potential technical advancement. Companies will be extremely conservative with new technologies. That's why it has taken the pharmaceutical and biotech industries about a decade to seriously use isolation technology, he says.
Yet the pharmaceutical industry used glove boxes many years ago – an early type of isolation technology – and then slowly adopted the use of cleanrooms. Meanwhile, isolation technology has been “rediscovered,” and its use is increasing.
The most contentious issues are those that put the same need for laminar flow air in a cleanroom as a standard for isolators. Air velocity requirements of 90 feet per minute arising from Fed-Std-209B are still included in many pharmaceutical guidelines, despite that the requirement was deleted in 1987. This increases operating costs.
Air changes are a rule of thumb rather than a standard. To keep people comfortable in a cleanroom, air changes are needed. Their relevance for isolators is unknown.
“Class 100 and laminar air flow are embedded in FDA rules. But in an isolator, why would you need laminar air flow? Isolators are not miniature cleanrooms. Thinking this is very wrong,” Agallaco says.
The FDA requires them to be placed in a Class 100,000 cleanroom while the European equivalent of the FDA, the Medical Control Agency (MCA) says it should be in a Class 10,000 room. The isolator industry wants the surrounding environment to be unclassified, but it's not likely the FDA will allow this.