Revisiting Interventions in Aseptic Processing - Pharmaceutical Technology

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Revisiting Interventions in Aseptic Processing
The authors revisit their previous effort to refine the terms that describe interventions and to dispel confusion that arose after the original article was published.

Pharmaceutical Technology
Volume 35, Issue 4, pp. 69-72

Corrective interventions. Corrective interventions are operator-performed activities required because of a fault or difficulty in the execution of the process. These interventions are necessary to address problems with equipment, materials, or procedures that require action to return the process to proper operation. Typical reasons for corrective interventions include container breakage, component misfeed, product leak, weight or volume adjustments, and equipment malfunction that interrupts operations.

The need for corrective interventions during an aseptic operation can vary substantially and can be affected by factors largely within the firm's control. In an ideal world (e.g., one with perfect equipment, materials, components, and procedures), it is conceivable that an aseptic process could be executed without the need for a single corrective intervention. Although this situation might not seem possible, it is reality for a substantial number of aseptic processing systems that use advanced technologies. However, even with less technology, the goal should always be to minimize the incidence of interventions. Corrective interventions are the result of one or more of the following causes:

  • Components with great variability in either specification or preparation that result in difficulties in subsequent processing
  • Poorly designed equipment that requires frequent adjustment or difficult assembly
  • Loosely defined setup procedures that result in variable performance.

At the present time, the incidence rate of corrective interventions can be expected to vary. Differences in the product, container, and closure can influence the need for interventions. When a line requires extensive adjustment during the set-up (i.e., inherent interventions), its operating performance likely will vary, even when the materials are unchanged, and the need for corrective intervention will also vary. Our industry should be seeking to reduce corrective intervention rates (actually interventions of all kinds) with the goal of completely eliminating them.† The Akers–Agalloco method provides a means for reviewing interventions with respect to their frequency, proximity, and criticality, and provides guidance for the development of criteria that can evaluate their impact (2, 3).

Three subcategories of corrective interventions warrant further discussion. Critical interventions are manual activities that involve repeating a portion of the initial setup. The risks associated with manipulating sterilized product-contact parts must be considered comparable to those associated with initial setup. Given the nature of the tasks required, an extensive clearance of the processing environment is generally required. The only factor that would not require clearance would be the use of separative technologies to mitigate the risk associated with critical interventions.

During the execution of an aseptic process, a situation may call for a heroic intervention, one that entails an inordinate amount of risk. The first inclination of many operating personnel may be to perform the intervention regardless of the associated risk. Caution is in order when the intervention requires activities likely to result in contamination. As a general rule, certain activities should never be permitted in conjunction with an aseptic process because they violate the principles of aseptic technique.

The execution of an aseptic process may require a new intervention, one that has not been considered previously (see the following section). Before proceeding with a new intervention, its consequences should be evaluated. The decision to proceed with a new intervention should be made by supervision and evaluated in the release decision. Again, unusually intrusive new interventions could be allowed in processes that use separative technologies such as isolators. In such cases, provided isolator integrity is retained, the risk of contamination caused by humans is negligible.


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