Understanding Overkill Sterilization: An End to the Confusion - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Understanding Overkill Sterilization: An End to the Confusion
The author clarifies the definition and objectives of overkill sterilization for steam sterilization cycles. Current sterilization practices are reviewed and the validation difficulties associated with the various definitions of overkill sterilization are explored.

Pharmaceutical Technology

The half-cycle method

To support the minimum PNSU, some practitioners adopt the half-cycle approach in which a 106 population of a resistant indicator is inactivated during the validation effort, and then the exposure period is doubled in routine operation. It relies on simple mathematics. Killing a BI with an initial population of 106 in the half-cycle validation study means at least a 9-log reduction has been attained. (A routine sterilization cycle with double the exposure period projects to >18-log reduction). This assumes the bioburden is identical in count and resistance to the BI, which is virtually impossible in the real world. The PNSU for a typical bioburden microorganism using this approach could easily exceed 10–200 or greater (see Table II for an example of half-cycle using an 8-min validation cycle and 16-min routine cycle with an initial microbial population of 106).

Figure 3
Figure 3 represents this process and the effect on the BI microorganism. (The D 121 value of the BI in Figures 3–6 is approximately 1 min.) The slope of the death curve, which depicts the number of surviving microorganisms at a time point, is known precisely only during the survivor-curve region where the number of survivors can be readily determined. The numbers of potentially surviving BI organisms in the fraction-negative region can be estimated using various methods requiring multiple challenge units exposed at cycles where some but not all of the BIs are rendered sterile. Extension of the death curve below a survival probability of 1 10–2 to 1 10–3 assumes that the death curve is logarithmically linear. This is a reasonable assumption because microbial death follows essentially first-order kinetics.

The confirmation of a 1 10–6 PNSU using any microbial challenge available can only be assumed, but it can be assumed with a high degree of confidence based upon biological lethality data. This salient point must be accepted without question. Irving Pflug has explained, "Accept that while the objective of a sterilization process may be a PNSU of 10–6, we cannot directly measure microbial levels of less than one surviving microorganism in 10 to 100 units (from 10–1 to 10–2). Therefore when designing or validating sterilization processes, we use indirect methods, so we have real measurements that are equivalent to our nonmeasurable PNSU of 10–6" (9).

Figure 4
In a sterilization validation study using an initial BI population of 106 spores per indicator, 20 strips per study, and three replicate runs in which no survivors are observed, the log reduction demonstrated requires approximately 9 logs (106 20 3 = 6 107 reduced to zero survivors) (see Figure 4).

Figure 5
If this process is considered the half cycle, then the full cycle (with twice the exposure time) is depicted in Figure 5.


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

Which of the following business challenge poses the greatest threat to your company?
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
Building a sustainable pipeline of products
Attracting a skilled workforce
Obtaining/maintaining adequate financing
Regulatory compliance
View Results
Eric Langer Outsourcing Outlook Eric LangerBiopharma Outsourcing Activities Update
Cynthia Challener, PhD Ingredients Insider Cynthia Challener, PhDAppropriate Process Design Critical for Commercial Manufacture of Highly Potent APIs
Jill Wechsler Regulatory Watch Jill Wechsler FDA and Manufacturers Seek a More Secure Drug Supply Chain
Sean Milmo European Regulatory WatchSean MilmoQuality by Design?Bridging the Gap between Concept and Implementation
Report: Pfizer Makes $101 Billion Offer to AstraZeneca
Medicare Payment Data Raises Questions About Drug Costs
FDA Wants You!
A New Strategy to Tackle Antibiotic Resistance
Drug-Diagnostic Development Stymied by Payer Concerns
Source: Pharmaceutical Technology,
Click here