2 nonroutine interventions within 2 feet: 2 × 3 × 2 = 12
1 critical intervention: 1 × 5 × 3 = 15
Weighted interventions/h: 12 + 4 + 9 + 12 + 15 = 52
The score should be based on the number of interventions observed or the maximum allowed. The ideal number of required interventions
is always zero.
The weighted number of interventions (normalized for criticality and proximity) per hour should be determined first. A longer
evaluation period provides a more accurate assessment, as does averaging the number of observed interventions over the entire
batch or multiple batches. The role of container and closure consistency in determining handling requirements is automatically
included when determining intervention risk in this manner.
Containers/hour. The number of containers per hour is the actual number of units produced during a one-hour period, not the theoretical line
speed per minute multiplied by 60. Determination of this value over a longer period of time is preferable for the sake of
accuracy. Do not include periods when filling is intentionally stopped for activities such as lunch, breaks, or shift change.
Include in the calculation those times when the fill is interrupted by interventions of any type. Divide these values by each
other to determine the number of interventions per container. Again, a lower number is desirable. This value is the intervention
), expressed as follows:
(normalized interventions/h) ÷ (containers/h) = interventions/container or intervention risk (I
Adjusted product-filling risk
Estimate the total risk from filling (for either manual or machine fills) by incorporating the remaining variables associated
with the filling process: container size, complexity, container introduction method, closure-handling technology factor, and
process duration (see Table V).
Multiply the intervention risk by the process duration in hours, the container design factor, container feed factor, closure
feed, aseptic personnel factor, and the technology factor.
Table V: Aseptic filling.
× fill duration × container factor × container feed factor × closure feed factor × novelty factor × product factor = contribution
to risk from aseptic filling
The longer the process duration, the greater the possibility that at least one unit will be contaminated because of the increased
number of interventions. Multiplying the intervention risk by the length of the process emphasizes the effect of filling speed
and includes consideration of fatigue as a factor in causing contamination.
Multiplying the resulting number by the product and technology factors adjusts for the varying levels of contamination potential
associated with various aseptic technologies and product formulation types.
Table VI: Lyophilization process (if present).
Lyophilization risk. Lyophilization risk is associated with the time that filled components are exposed to the environment, between first exposure
and closure, as well as with the handling practices, lyophilizer sanitization** (see endnotes) and sterilization practices,
and environmental technology (see Table VI). The equation is as follows:
lyophilization risk contribution = loading time × lyophilizer sterilization factor × load factor × transfer factor × tray
factor × technology factor