Aseptic processing guidelines under consideration

12/01/2002

by Hank Rahe

I recently attended a public hearing where the proposed revision of aseptic guidelines for manufacturing parenteral products was presented for comment by the FDA. While there was universal concern in the room about the content of the document, the mood was decidedly mixed.

Some complained that the document was "too general," while others complained it was "too detailed" to allow for future innovation. However, barrier isolation technology was the one item in the document that seemed to receive consistent agreement. The consensus was that it [barrier isolation technology] should be encouraged as a means of aseptic processing because it offers improved sterility assurance over traditional cleanroom technology.

The text has reassured us that the U.S. Food and Drug Administration (FDA) has recognized the advantages of removing people from the critical processing zone. The agency has also indicated that steps need to be taken to review the excessive burdens placed on the validation of barrier isolation systems. Although any equipment or process that involves handling drugs that will be injected directly into the human body needs to be approached with caution, many feel that an extra burden of "system proof" was placed on barrier isolator systems.

Hopefully, the new approach will be risk-based and each component of the barrier isolator will be evaluated for risk of contamination and the proper safeguards will be put into place.

The risk-based evaluation of barrier isolators should be to benchmark against current cleanroom practices and to establish a baseline or minimum acceptable practice. The positive features of the barrier isolators—such as eliminating personnel in the critical processing zone—provide the advantages.

The two technologies, barrier isolators and cleanrooms, should be directly compared in terms of movement of materials into and out of the environment, personnel interaction, cleaning and sanitizing, as well as pressure control. Each of these components introduces risks, and a comparison would allow criteria for each technology to be established.

Examples of the extra burden placed on validation of isolators are glove testing and transfer of materials into and out of the environments. I have never known the gloves used in a cleanroom to be tested for integrity, before or after use.

This is not the case with barrier isolators. I suppose a case could be made that there is a potentially higher risk due to the surrounding environment, but the reaction may not match the risk.

The second example is transfer of materials: This needs only the vision of a person "wiping down" materials in an airlock compared to a "high level" of concern for potential contamination on rapid transfer port (RTP) seals.

An experienced task team could be put together to use the risk-based approach to develop the proper guidance detail to answer both regulatory and industry needs. This team, considering current practices, can access the critical elements that provide a safe product environment.

The environment should be defined by both physical expectations and documentation requirements with the work product of the task team being at two different levels of detail.

The first is adequate regulatory guidance to assure the continued manufacturing of quality products. Second would be the outlining of acceptable practices for the construction, operation as well as the documentation of facilities where the products are produced and tested. This approach would reduce the uncertainty that exists in industry, which is the leading factor in creating excessive validation requirements for barrier isolator systems.

While many things need to be addressed in the new guideline, the corner stone is facility guidance, whether it's a cleanroom or a barrier isolator.

Hank Rahe is director of technology for Containment Technologies Group and is a member of the CleanRooms Editorial Advisory Board. He can be contacted at [email protected].