The Akers–Agalloco Method - Pharmaceutical Technology

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The Akers–Agalloco Method

Pharmaceutical Technology
Volume 29, Issue 11

Aseptic compounding contribution

Table III: Aseptic compounding.
Processes that require substantial amounts of aseptic processing during formulation have an increased risk that must be factored separately from the aseptic filling process. The number of personnel interacting with sterile materials; the duration of the process, including setup and execution (exclusive of hold times where the sterile material is secured and there is no personnel activity in the environment); and the technology used for the process are factors in this area (see Table III). Because these processes generally involve frequent human intervention, interventions are not considered separately. This contribution is present in the production of even the simplest products in which the only postfiltration activity involving sterile materials is associated with sampling or verifying filter integrity.

The process time, including any required aseptic setup for compounding, is multiplied by a novelty factor—based on experience of personnel, equipment, and process—to determine the aseptic compounding contribution to process risk, which can be expressed as follows:

aseptic compounding risk contribution = process duration novelty factor aseptic personnel factor

Aseptic setup contribution

The assembly and setup of filling equipment require direct human manipulation of sterilized equipment and tools within the critical environment. In some firms, only the most experienced personnel, whose proficiency in the required task has been confirmed by a successful media fill, are allowed to perform this task. The hands-on nature of this activity often requires evaluation separate from that of the fill process. The duration of the setup, which reflects the sophistication and complexity of the filling equipment and the uniformity of the components, should be factored into this activity. Because this activity is almost entirely accomplished by humans, related process interventions are not considered separately.

Typically included in this activity are product connection and introduction, initial weight and closure systems checks, and any other relevant activities, including environmental monitoring during this assembly and setup process. The additional setup concerns related to suspensions, creams, ointments, and powders are factored into the setup duration time, as are other elements such as stopper and vial uniformity, inert gassing system installation, and the more demanding requirements for double-chamber filling and other more complex package designs (see Table IV). Product-formulation factors also are incorporated into contributions from the aseptic execution. The location of sterilizing-grade filters in the product delivery system affects the risk of contamination of a filled container. The aseptic setup risk is expressed as follows:

Table IV: Aseptic filling setup.
aseptic setup risk contribution = setup duration complexity factor product delivery factor novelty factor aseptic personnel factor

Aseptic-filling process contribution

The perfect intervention is the one you don't have to perform. When evaluating aseptic processing, one must focus on the need to avoid interventions and, when they are unavoidable, to minimize their influence. Intervention management during aseptic processing has received increased attention with an increase in the importance of interventions (1). A recent article about intervention management provides the following definitions and examples related to aseptic filling activities (as opposed to setup or changeover):

Routine interventions are activities that are inherent parts of the aseptic process and integral parts of every batch. Typical routine interventions include:

  • periodic component replenishment;
  • periodic fill weight or volume checking and verification;
  • fill weight or volume adjustment;
  • environmental monitoring;
  • product sampling;
  • filter integrity testing;
  • product container replacement;
  • any other interventional activity that is an integral part of the process (12).


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