Quality Control - Microbial Testing: Rapid Microbiological Methods in Lean Manufacturing


Quality Control - Microbial Testing: Rapid Microbiological Methods in Lean Manufacturing

October 2010

Judy Madden, Vice President, Corporate Development, Celsis International, as featured in PFQ

Change can reduce costs, waste
By stripping waste and other steps that have no value from the production process, lean manufacturing can result in significant savings. But why stop there? If your company uses traditional testing methods to release its products to market, the adoption of rapid microbiological methods (RMMs) could be one of the most important additions you make to your company’s lean initiatives.

Lean quality is achieved by extending the principles of lean manufacturing to microbial testing. RMMs are being adopted by an increasing number of pharmaceutical companies, contract manufacturers, co-packers, and testing operations around the world to reduce lead times while ensuring product safety. Implementing rapid methods can unlock huge savings by shortening your microbial hold times to just 24 hours for microbial limits and cutting sterility testing time by more than 50%.

How Rapid Methods Work
Products that are susceptible to microbial contamination but are expected to be shipped contamination free are screened before being released into distribution. That screening adds multiple days to the production cycle and extends lead times. Micro-screening typically takes three to seven days for microbial limits testing and 14 days or more for sterility. That’s a long time to wait when you have a good production process in place that is turning out products free from bioburden almost all the time. The wait time is frustrating and expensive.

Well-validated rapid methods are just as effective as traditional microbiological methods, but faster. Results can be delivered in as few as 24 hours using AMPiScreen technology. This amplified bioluminescence method combines the use of adenosine triphosphate (ATP), the gold standard of rapid detection, with a patented enzyme technology to deliver accurate results even faster.

All living organisms contain the compound ATP, a vital part of energy metabolism. When ATP is detected in the standard bioluminescence test, a reaction occurs that generates a photon of yellow-green light, similar to that of a firefly. Although it is a very sensitive technique, it is limited because an organism can contain only a finite amount of the metabolite ATP.

Amplified ATP uses enzymes to generate an almost unlimited amount of ATP. After 25 minutes, for example, the amount of ATP can be 1,000 times greater than the organism originally contained. As a result of this amplification and the reduced dependence upon microbial growth for detection, Amplified-ATP bioluminescence provides even faster results when used to screen for microbial contamination.

Benefits of Rapid Methods
When deciding whether to implement RMMs as part of your company’s lean initiatives, you should first consider the benefits.

  • Financial Benefits: Hundreds of manufacturing facilities worldwide have saved millions by implementing rapid methods, but how much could your company potentially save? At Celsis, the answer can be calculated using readily available data from your company’s finance, manufacturing, and quality departments. This information is used to populate the Celsis Value Creation Model, which then projects your company’s customized five-year net present value (NPV) and payback period for implementing a Celsis rapid detection system. In our experience, most companies realize payback on their investment in just six to nine months, with an average five-year NPV in excess of $500,000 per facility.
  • Cost-Per-Test Savings: While there is an increased cost for assay materials, the operational and financial benefits far outweigh the expense. When you combine all of the benefits listed above, the cost of rapid methods per assay is far less than that of traditional methods. If your company stores batches or products awaiting test results, you will benefit by reducing the working capital investment in inventory. By reducing your investment in inventory, you will benefit by clearing out space in the warehouse. If you carry safety stock, you will further benefit from cutting it down to size. If you manage a brand, you will benefit by offering your distributors a faster response time and by reducing the risk of contaminated product reaching consumers.
  • Expedited Order Fulfillment: Going lean reduces the time it takes you to produce, package, and/or test products, allowing you to fill orders quickly and more efficiently. Reducing the time required to complete orders leads to faster invoicing and faster payment. Additionally, without the need to house quarantined finished products, in-process and raw materials, and safety stock in micro-hold, your company will have extra warehouse space that will increase its capacity for additional business.
  • Reduced Working Capital Requirements: By reducing inventory requirements, you can manage a shorter cash cycle and dedicate more dollars to building your business rather than financing the conversion of raw materials to finished goods. This reclaimed working capital can then be used for productive purposes: growing revenue, developing new product, or funding other projects in functional areas that will bring value to the organization.
  • Enhanced Risk Management, Faster Recovery: What happens when there is a contamination event? At these times, when so much is at risk, the benefits of rapid methods are actually doubled. By improving efficiency in your product testing, you also reduce your recovery time if a contamination occurs. The faster a problem is identified, the more quickly you can begin corrective action and recover. RMMs reduce the potential negative impact on your customer relationships and minimize risk for your bottom line.
  • This benefit is not limited to a contamination event involving product released into distribution; it also includes those detected by your current traditional methods. The cost and timing associated with recovery can be significant and, to the extent that customer service is impacted, those costs can be even greater and more difficult to quantify.
  • Reduced Waste: Not only do rapid methods reduce the amount of product that must be disposed when a contamination occurs, they also reduce waste in testing supplies. Think about the vast volumes of broth, containers, and/or plates that your company goes through each month to run the multiple assays necessary to screen a single sample of product. With rapid methods, these bulky traditional testing supplies are significantly reduced. For example, the AK-based assay effectively screens for bacteria, yeast, or mold contamination from a single broth enrichment, and the assay requires only a small cuvette.

Adopting Rapid Methods in Pharma
The pharmaceutical industry is an ideal environment for a rapid absence/presence screen. The manufacturing and packaging of pharmaceuticals today are conducted under conditions that produce a “clean” product at least 99% of the time. If a positive is rarely expected, there is rarely anything to enumerate.

With 99% or more of products testing negative for microbial contamination, lean principles suggest that a simple, rapid absence/presence screen will provide the actionable information necessary to manage the majority of production in a time- and cost-effective fashion. That leaves less than 1% of production to be managed on an exception basis for further evaluation against product specification. The use of enumeration technologies to “count to zero” typically results in limited implementation because of cost, limited product applicability, protocol complexity, or resource limitations. Quite simply, if the technology can’t be broadly implemented, then the financial and operational efficiencies won’t be realized.

Transitioning pharmaceuticals and other regulated products to a rapid release method is straightforward and is, in fact, encouraged by many global regulatory bodies, including the U.S. Food and Drug Administration (FDA). The preferred approach is to “tell them what you’re going to do, do it, and then tell them that you’ve done it.” That is a reasonably accurate description of the FDA’s comparability protocol. The centerpiece, or “do it” part, is validating the product or group of products for routine release using the rapid method. This typically entails side-by-side testing to ensure that the rapid method is as sensitive as the traditional method. During this stage, lab staff become more experienced and confident in the rapid system so that when the validation data are collected, the RMM is effectively implemented.

Your RMM provider may have regulatory compliance expertise on staff that you can tap into, as well as drug master files (DMFs) accepted by the FDA. The DMFs include data for specificity, limit of detection, robustness, ruggedness, and equivalence, and they can be used to supplement or streamline the validation of your rapid system. This may save significant time, both in your preparation and in the FDA’s review and approval process.

Controlling costs and operating more efficiently are priorities for everyone in the pharmaceutical value chain. Rapid microbial screening is a significant opportunity for manufacturers and contractors to reduce costs, risk, and working capital requirements through a leaner, more efficient quality screening process.


Judy Madden is Vice President of Corporate Development at Celsis International Ltd., a manufacturer and distributor of rapid microbiological testing equipment and reagents. Reach her at (312) 476-1200 or at rdinfo@celsis.com.

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