Sterility by design
The authors's article titled "The Myth Called 'Sterility'" reviewed the current controls for aseptic processing (4). In that
article, the authors stated that the existing controls for assessing aseptic processing performance are largely inadequate
to ensure the sterility of the materials being produced. Although industry might not understand it fully, reliance on sampling
and monitoring is no longer adequate. In fact, some unscientific compliance approaches imply that sterility can be monitored,
validated, or tested into a process.
The capabilities of modern aseptic processing exceed the ability of the current measurement tools. The authors previously
outlined the components of aseptic operations that should be considered to attain sterility. The description of these components
focused on design considerations that minimized or eliminated the need for operator intervention. The concepts embodied in
that article are perhaps most directly applicable to the design of new aseptic processing facilities, or to equipment or component
selection. Nevertheless, the article includes the following recommendations that can be applied without significant capital
- Glass and plastic containers, elastomeric closures, and other primary package components with tight acceptable quality levels
can reduce the need for interventions.
- Robustly controlled and validated preparation and siliconization procedures that are consistent can reduce handling difficulties
and the interventions needed to remediate them.
- Applying the suggestions about intervention management can help reduce the impact of interventions.
Sterility—or, more accurately, microbiological safety suitable for injectable medicines—is accomplished through design more
than any other means. Excessive tolerance of interventions, whether inherent or corrective, amounts to settling for an inferior
design. Given the negative outcomes that can result from interventions, the goal must be to minimize them. Facility, equipment,
and procedures must be designed, specified, and defined with that intent.
The authors' vision of the future is one in which advanced aseptic processing is universal and direct human interaction with
sterile materials never occurs (5–8). Until these systems are universal, the need for aseptic interventions will persist,
and firms should organize their interventional activities to mitigate the risk of contamination. The authors maintain that
interventions should be avoided at all times. It is instructive to remember Hank Avallone's important lesson: "It is useful
to assume that the operator is always contaminated while operating in the aseptic area. If the procedures are viewed from
this perspective, those practices which are exposing the product to contamination are more easily identified" (9).
James Agalloco* is president of Agalloco & Associates, PO Box 899, Belle Mead, NJ 08502, tel. 908.874.7558, firstname.lastname@example.org
. He also is a member of Pharmaceutical Technology's editorial advisory board. James Akers is president of Akers Kennedy & Associates.
*To whom all correspondence should be addressed.