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

Latest Issue
PharmTech

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.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

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

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here