James P. Agalloco

Any aseptic processing technology that allows intervention by gowned personnel during operation cannot be considered an advanced technology. Although a standardized definition of restricted access barrier systems has been developed, these systems fall well short of being classfied as advanced technologies.

There are few, if any, valid reasons not to install an isolator in a new aseptic processing facility.

The authors present a new approach to risk assessment for aseptic processing that emphasizes the contributions of personnel.

The complete elimination of human-derived contamination is possible only with the elimination of human intervention.

The sterility testing of samples from an aseptic process may be considered an entirely separate aseptic process that is subject to the same types of adventitious contamination as the aseptic process itself.

This article outlines a comprehensive approach for organizing a firm's aseptic operations, including planning for routine and nonroutine interventions, establishing effective process simulations, and determining which vials to incubate.

The authors review current industry practices and regulatory expectations for the aseptic processing of sterile drugs. They compare and outline critical issues in current manufacturing technology and capabilities with regulatory requirements.

FDA's draft guidance on aseptic processing contains some inherent difficulties, including unrealistic expectations of sterility and microbial quantification, an absence of harmonization with international rules, and failure to support new technologies or a risk-based approach. The authors propose a science-based alternative.

In the concluding part of this article, the authors address diffusive-airflow imprecisions and measurements as well as automated integrity-test equipment, variations in bubble-point measurements, and the identification of a "sterilizing" filter.

In Part I of this article, the authors summarize the principles of various integrity tests, including their performance and purpose.