Nonroutine interventions are a significantly greater concern than routine interventions because their frequency is substantially
lower than that of routine interventions. In contrast to routine interventions, the execution of nonroutine interventions
cannot be as narrowly scripted. In the article cited previously, the user is encouraged to define how to perform interventions
of all types, train personnel in those practices, and adhere to them during process simulation and routine production. That
is sound advice, but there are simply no means to orchestrate nonroutine interventions so that they conform to the predefined
practices. During an actual process, nonroutine interventions may vary somewhat from expectations, and a company may be forced
to rely on adaptations by the operator to execute them successfully. For this reason, the authors place greater emphasis on
any nonroutine interventions that must be performed. The following definition and list come from the same reference:
Nonroutine interventions are activities that are predominantly corrective and may not be a part of every batch. Although in
theory nonroutine interventions may not be necessary during the aseptic process, in practice such interventions are almost
always required to correct some anomaly. Some common nonroutine interventions involve:
- stopper misfeeds or clumping;
- fallen, broken, or jammed containers;
- defective seals on containers;
- product spillage or leakage;
- product filter change;
- sensor adjustments or replacement;
- filling-needle replacement;
- fill-pump replacement;
- stopper-bowl changes;
- timing adjustments;
- conveyor or guide-rail adjustments;
- any other line malfunction requiring manual correction (12).
The aseptic-filling risk contribution can be determined using an approach designed strictly for manual fills and a more general
method for machine fills in which personnel fulfill only a supporting role.
The intervention risk is the number of times the individual parts of the package (e.g., vial or stopper) are handled to prepare a filled container, and is expressed as follows:
intervention risk for manual filling (I
) = touches per unit
The result is combined with the other relevant factors for aseptic filling found in the tables to define the overall risk
for manual aseptic filling.
The intervention risk for any container is defined as the number of times the container must be handled during the aseptic
process. In manual filling, that number is usually greater than 1. Machine filling has an intervention risk of less than 1
(see the "Machine fills" section).
Manual filling must be considered the most risky of all aseptic processes because the minimum number of required interventions
to fill and seal a container is greater than one.
Interventions during machine filling are substantially fewer, and thus of lesser impact, relative to manual fills. Intervention
, with respect to criticality factors considered, is the distance from the exposed product contact parts and components. Critical
interventions (e.g., replacement of fill pumps or other critical dosing equipment) are scored as 5, as are any aseptic connections made or remade
after the initial setup. All other interventions within one foot of exposed product contact parts or components parts are
scored as 3 on every occurrence. Interventions within two feet are scored as 2. Interventions outside two feet are scored
as 1. Routine interventions that are an inherent part of every process are weighted as 1, and nonroutine (or corrective) interventions
are weighted as 3.
Number of interventions. Calculate or visually confirm for a period of not less than one hour during the process all of the interventions, routine
and nonroutine, required during the process. Multiply each by the appropriate proximity and type score. Determine the weighted
number of interventions per hour by adding these values. For example:
4 routine interventions within 1 foot: 4 × 1 × 3 = 12
2 routine interventions within 2 feet: 2 × 1 × 2 = 4
1 nonroutine intervention within 3 feet: 1 × 3 × 3 = 9