ASEPTIC PROCESSING: TWO - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing - page 262

TABLE 10.9 The Probabilities of Detecting a Nonsterile
Unit with Varying Percentages of Unit Contamination
Frequencies [61]

Probability of Detection

Frequency of Probability of

Contaminated Units Positive Test

1.0 (100%) 1.0 (100%)

0.1 (10%) 0.86 (86%)

0.01 (1%) 0.18 (18%)

0.001 (0.1%) 0.02 (2%)

10.8.3 Superior Assurance of Product Quality is Achieved by Quantitative
Risk Assessment
The previously described practical and technical constraints of sterility testing
provide a profound justification for applying more innovative, quantitative risk
assessment and risk-based approaches to assuring sterility of an aseptically man-
ufactured product. The paradigm combining QbD, quantitative risk assessment
integrated into pharmaceutical quality systems as defined in ICH Q8, Q9, and
Q10 offers a realistic, practicable means of assuring product sterility to a far
superior statistical basis.
Despite the currently accepted adequacy of the sum contribution of all tech-
nologies, practices, in-process tests, monitoring systems (qualified on a regular
basis by process simulations), and final product testing, the disposition of an
aseptically processed product can be greatly improved in terms of rigor and
objectivity using QbD and quantitative risk assessment. For a considerable time,
the food industry has successfully applied microbial risk models that model, cal-
culate, and quantify the risk to the end consumer from microbial hazards derived
from sources along a logic chain or risk pathway [62,63]. The fundamental logic
path and associated microbial dynamics described by these quantitative micro-
bial risk assessment methodologies is clearly mirrored by the application of risk
hierarchies fundamental to aseptic processing risk assessments. Generating a risk
pathway (essentially equivalent to a process flow) by applying risk hierarchies

TABLE 10.10 The Probabilities of Passing a Sterility Test with
Varying Percentages of Unit Contamination Frequencies [61]
Probability of Passing Test

Frequency of Probability of Passing

Contaminated Units Test ( n = 20)

1.0 (100%) 0

0.1 (10%) 0.14 (14%)

0.01 (1%) 0.82 (82%)