Increase Speed to Market: Utilizing Enhanced ATP Bioluminescence for Rapid Microbial Detection - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Increase Speed to Market: Utilizing Enhanced ATP Bioluminescence for Rapid Microbial Detection
A new adenosine triphosphate bioluminesence technology allows manufacturers to detect the presence of microbial contamination within 24–48 hours rather than the 3–5 days required by traditional methods.

Pharmaceutical Technology

Pharmaceutical manufacturers around the world have recognized the economic benefits of implementing adenosine triphosphate (ATP) bioluminescence for the rapid microbial screening of a wide range of raw materials, work in-process, and finished goods. One way to achieve this is with the Celsis Rapid Detection System, which more than 450 industrial facilities on six continents have implemented.

The Celsis ATP bioluminescence technology detects the presence of microbial contamination within 24–48 hours rather than the 3–5 days required by traditional methods. This translates to quantifiable financial benefits in a few principle areas of manufacturing operations. For example, by reducing quarantined inventory and manufacturing cycle times, manufacturers also reduce their safety stock and working capital requirements. This leads to better utilization and return on invested working capital. In addition, by using rapid screening, contamination is identified faster, corrective action is more timely and effective, and losses associated with contamination are minimized.

Although ATP bioluminescence is a very sensitive technique that is widely accepted and broadly used, it does have its limitations for certain product applications. Definitive detection is based on having a sufficient quantity of microbial ATP present that can generate a light signal that is distinguishable from product background. If the product itself has a high background based on ATP from non-microbial sources, or the product is contaminated with an adaptive, slow-growing organism, then definitive detection becomes more difficult.

Companies have overcome these two technical issues by moving to the Celsis "AKuScreen"which utilizes a two-step, two-enzyme system that further decreases time to result. The AKuScreen technology is based on the amplification of microbial ATP and is not constrained by the finite amount of ATP available in a standard bioluminescence assay. Amplification of microbial ATP is accomplished by exploiting microbial adenylate kinase (AK) that is also present in all living organisms. It is possible to use AK to generate almost unlimited amounts of its product because this is an enzyme, rather than a metabolite. The reaction catalysed by AK is:

This amplification allows for greater differentiation and a more sensitive measure of microbial contamination. Therefore, companies can more effectively screen products with elevated background of nonmicrobial ATP and products contaminated with adaptive, slow growing organisms. Also, the time to result is reduced to 18–24 hours compared to 24–48 hours with standard ATP bioluminescence and 3–5 days with traditional methods.

How it works

Applying Celsis technology, the adenylate kinase (AK) enzyme in a bacterium can be made to produce within one minute approximately 40 times its current volume of ATP. If the reaction is allowed to continue for 25 minutes, the amount of ATP can be 1000 times greater than what the organism contained originally. The end result is a much higher signal (positive result) when compared to standard bioluminescence.

Another benefit of the core technology is the high signal-to-noise (S/N) ratio. This ratio is an indicator of a test kit's ability to distinguish between a contaminated sample and regular background generated from a product sample. AKuScreen exhibits a significantly higher S/N ratio than the standard ATP bioluminescence assay. As the AK assay continuously generates ATP, sample background noise is proportionately smaller as compared to traditional ATP bioluminescence. Additionally, because of this strong signal, the assay read time can be further reduced, minimizing the impact of background noise generated from non-microbial ATP in the sample. This increases the sensitivity of the assay and removes any uncertainty of the end result.

A number of companies have derived value from deploying the rapid AK method of microbial detection.


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