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

Because the lethality of the full cycle cannot be demonstrated using a biochallenge and recalling that a 106 BI challenge is destroyed in the half cycle, the log reduction delivered to the BI must be assumed. Using the assumed log reduction for the half cycle and doubling the dwell time, the log reduction for the BI in the full cycle can be estimated at 18 logs and easily meets the overkill definition of a minimum 12-log reduction of a BI with a D-value of 1 min (assuming the BI had a D 121 > 1 min) as is typical in nearly all overkill validation studies.

Figure 6
There are several inherent assumptions with the half-cycle method. The first assumption is that the bioburden would be as numerous and resistant as the BI. Second, it is assumed that the complete destruction of the multiple BIs in triplicate studies demonstrated a 9-log reduction of that BI. Finally, the death curve of the BI is assumed to be linear in a region where it cannot be experimentally determined.

Sterilization process objective

The routine sterilization of items in any sterilization process is intended to destroy the bioburden microorganisms that might be present on or in the materials being processed, regardless of their initial population and resistance. The goal is constant: to attain a minimum PNSU of 10–6. Consider the following definition of overkill sterilization as being consistent with what process expectations should be:

Overkill sterilization is a process where the destruction of a high concentration of a resistant microorganism supports the elimination of bioburden that might be present in routine processing. That objective can be demonstrated by attaining any of the following: a defined minimum F 0, a defined time-temperature condition, or a defined log reduction of a biological indicator.

This definition reflects the process requirement directly, with full recognition that bioburden organisms typically have minimal heat resistance. Destruction of the BI in high concentration requires time and temperature conditions far in excess of what is required to destroy the bioburden, and thus overkill is demonstrated.

Demonstrating a minimum PNSU of 1 10–6 for a sterilization process can be ensured only where the number and resistance of the microorganisms present on or in the items being sterilized is known. This can be accomplished definitively using any of the sterilization-cycle approaches described previously, and delivering that lethality is not restricted to the overkill method. It is supported by information about the relative resistance of the bioburden to the biological indicator in the BB/BI method in which partial kill of the indicator is sufficient to support the required minimum PNSU for the bioburden. With the overkill method, complete destruction of the resistant BI in high numbers is more than sufficient to ensure the minimum PNSU for any conceivable bioburden.

In everyday usage of sterilizing equipment, the BI is not present. The process is expected to confidently destroy the bioburden. In today's industry, we have numerous controls on the pre-sterilization bioburden, and in many instances, especially terminal sterilization, it is monitored for each sterilizer load.


blog comments powered by Disqus
LCGC E-mail Newsletters

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

What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Jim Miller Outsourcing Outlook Jim MillerOutside Looking In
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAdvances in Large-Scale Heterocyclic Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler New Era for Generic Drugs
Sean Milmo European Regulatory WatchSean MilmoTackling Drug Shortages
New Congress to Tackle Health Reform, Biomedical Innovation, Tax Policy
Combination Products Challenge Biopharma Manufacturers
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
Source: Pharmaceutical Technology,
Click here