PDA Examines Isolation Issues

Erik Swain

Now that barrier isolation technology is coming into wide use, many feel the pharmaceutical industry needs to challenge previous theories and assumptions about the systems by looking at the evidence of how they really work and what sorts of things cause real problems.

That was the purpose of the Parenteral Drug Association's (PDA; Bethesda, MD) forum "Isolation Technology: User Issues," held April 29–30, 2002, in East Brunswick, NJ. Presenters and attendees shared their practical experiences in the hope of providing the industry with a clearer picture of how the systems should and should not work.

One issue, said James E. Akers, president of Akers Kennedy & Associates (Kansas City, MO) and a past president of PDA, is that there is a lot of "misunderstanding of risk analysis and confusion regarding operational requirements." He noted that some firms and regulators have placed cleanroom paradigms on isolator rooms when they are not needed because the risk of contamination in an isolator is much less than it is in a cleanroom. However, he added, some proponents of the technology have overstated what it can accomplish, which has led to unrealizable expectations.

"We got tied up by setting ‘terminal sterilization' as a standard, but the reality is, we can't prove that," he said. "That has led to unreasonable decontamination standards and paranoia regarding items such as sterility assurance levels and environmental monitoring."

Air supply and air velocity issues for isolators, for example, have often been set using cleanroom specifications, but they should not because they are "different engineering systems" which "do not have the same issues concerning human-borne contamination," he said.

Another area where cleanroom standards have been misapplied is in stopper bowl decontamination, Akers said. In cleanrooms, they must be autoclaved, resulting in a sterility assurance level of 10-6. But then they are set up manually, meaning a 10-6 claim after assembly is unlikely. While they are not autoclaved when used in isolators, they are not disassembled either and thus do not risk recontamination. So holding them to the same standard as that for use in cleanrooms may not be appropriate. "Risk analysis is called for," he said.

Much has been made of leakage in isolators, but that has been "blown out of proportion" in positive-pressure aseptic applications, because even when there is a leak, "contamination is prevented by air overpressure," he said.

The conference featured much discussion of glove breaches, identified by FDA as a major concern. As with other issues, presenters and attendees encouraged analysis of what the actual consequences are for different kinds of breaches and not reliance on theory.

Dennis Croll, director of manufacturing technology at Alkermes Inc. (Cambridge, MA), said his firm has developed a decision tree to evaluate how serious a glove breach is. If it can determine that a breached glove came in contact with product, it will reject the batch, but if the actual product appears not to have been in contact, and environmental monitoring tests are passed, it may end up accepting it, he said. The tree also lists the different procedures supervisors and operators should take once a problem is discovered.

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