Rapid microbial testing with adenylate kinase technology
September 2005
Manufacturers of personal care products (including skin care, cosmetics, personal hygiene and home cleaning products) have been challenged over the past few years to improve operating income growth amid a variety of industry pressures. Playing a significant role among these pressures is the dispersion (or globalisation) of the supply chain. Products and/or raw materials that used to be sourced locally are now produced and distributed in other countries and different time zones. And while industry financials may reflect the reduced manufacturing costs resulting from producing in lower cost environments, the increased logistical challenges of supply chain dispersion are formidable and can be costly.
A 2003 study on the challenges of global manufacturing concluded that “the consequence of fast-growing value chain dispersion and accelerating innovation is complexity. It is an explosive concoction. Such complexity is blowing to pieces the iron-grip control supply chain managers used to have in co-ordinating their operations. The task of managing and co-ordinating [activities]…becomes geometrically more difficult.”1 Add to this an increasingly demanding and powerful customer base, and the challenge to supply chain managers is significant.
Central to any strategy to maximise the return on invested working capital is the concept of right-sizing inventory; that is, reducing the on-hand quantities and optimising the placement of various inventories in the total supply chain – from raw materials, to products in process, to products packaged for distribution. Calculating acceptable inventory levels for each stage of the supply chain takes into account several variables including manufacturing capacity, manufacturing lead times and distribution lead times. In addition, consideration must be given to goals such as meeting corporate performance and customers’ service expectations. Finally, and perhaps most difficult, is the need to plan for the uncertainties of supply chain disruptions or demand variability. A study conducted by management consultant Accenture and Stanford University identified a “Focus on shortening the supply chain” on the top of its list of supply chain transformation principles.2 Companies today are investing tens of millions of dollars in software to more effectively manage their supply chains from supplier to customer; from end to end.
The cost of quality
Into this volatile environment of carefully balancing dependable customer service with one-world manufacturing and closely monitored inventories enters the fixed issue of product quality. The presence of micro-organisms in a personal care product can affect its quality, performance, shelf-life and the reputation of the brand to retailers and consumers alike. The microbial quality of the product is nonnegotiable – you must have it, and you either have it or you don’t. Unfortunately, while other manufacturing processes have undergone modernisation, automation and streamlining, certain microbial quality assurance testing methods have remained virtually unchanged. They are still based on the traditional microbiological methods identified nearly 100 years ago.
The personal care industry generally accepts that it takes from three to seven days to culture micro-organisms on specific agar-based media to levels that can be detected as Colony Forming Units (CFU) which are visible to the naked human eye. It is also important to note that traditional microbiological methods are rife with time-consuming operations for laboratory staff as well as inefficiencies in detection of micro-organisms due to sampling processes and the probability of isolation from preserved products. The outlay required to accomplish testing using traditional methods is high, and ripe for change. The following example uses five days as the typical time frame for traditional microbial testing:
_ Five days of finished goods inventory sits idle in a warehouse awaiting test results before distribution. Meanwhile, production planners add five days to their replenishment lead times, directly impacting the amount of downstream safety stock that must be held in order to satisfy customer lead time requirements. In the most extreme case, five days added to manufacturing lead time may directly translate into five additional days of safety stock. In fact, for a product that might be formulated and packaged in two days, traditional microbial quality testing represents the single largest component of product lead time.
_ It is a fact that contamination will occur, despite all measures to prevent it. Using traditional testing, contamination may not be discovered for five days following the occurrence. This may mean that up to five days of additional production has been run through contaminated equipment, significantly increasing the economic impact of the event. Further, corrective action aimed at identifying the root cause of the contamination is hindered by the delay in getting started. Finally, the release of replacement product to distribution is also subject to microbial screening and therefore further delayed by the quarantine period.
If microbial screening could be accomplished faster, less working capital would be invested in inventory on microhold and in safety stock. Also, contamination would be identified faster, the losses associated with contamination could be minimised, and corrective action would be more timely and effective.
Rapid microbial methods
For the reasons described above, many manufacturing industries have sought out alternative, more efficient approaches to microbial testing while attempting to ensure that quality standards are maintained or improved. Innovations in the development of rapid microbial testing methods have gained greater recognition and have been adopted by many manufacturers. More specifically, over the course of the last decade adenosine triphosphate (ATP) bioluminescence technology has been broadly implemented by personal care and pharmaceutical companies for the rapid microbial screening of a wide range of raw materials and finished goods.
How is bioluminescence technology distinguished from traditional testing methods? All living organisms contain and utilise the nucleotide ATP as a vital part of their energy/metabolic systems. It is ATP that is released and detected by a standard bioluminescence test. Most familiar as the flash of a firefly tail, ATP rapidly reacts in the presence of luciferase to produce a photon of yellow-green light.
Bioluminescence methods use a very sensitive light reading instrument called a luminometer to dispense reagents into the product sample and measure the amount of light generated by the reaction; the amount of light is proportional to the amount of ATP present in the sample. ATP bioluminescence can detect the presence of microbial contamination within 24-48 hours resulting in significant cost savings and improved supply chain process efficiencies. But while it is a very sensitive, rapid technique, ATP bioluminescence is nevertheless limited by the fact that it is detecting a metabolite. Since a single organism can contain only a finite amount of ATP, a sufficient number of organisms must be present for definitive detection. Building on the proven success of ATP bioluminescence, Celsis International has developed an even faster, more sensitive method of detecting micro-organisms – adenylate kinase (AK) technology.
Adenylate kinase the ATP amplifier
Adenylate kinase, an enzyme, is another element vital to all living organisms for the maintenance of energy pathways and metabolism. To understand the impact of AK technology, it’s helpful to remember that enzymes are proteins used to catalyse, or initiate, other reactions without being consumed or altered by the reaction. The reaction catalysed by AK is:
AK
2ADP < >AMP + ATP
AK technology utilises adenosine diphosphate (ADP) and microbial adenylate kinase to catalyse the production of ATP.4 Given the ability of enzymes to effect reactions without being depleted or changed in any way, it is possible to use microbial AK to generate almost unlimited amounts of its products. Since ATP is one of those products, the longer the AK reaction is allowed to proceed, the more ATP is generated and the greater the bioluminescence signal.
In effect, AK technology is based on the production and amplification of ATP. As a general guide, in one minute the AK enzyme can be used to produce approximately 40 times more ATP than the organism originally contained. If the reaction is allowed 25 minutes, the amount of ATP can be 1,000 times more than the organism originally contained. Since the use of AK technology as the end-point detection method gives a significantly more sensitive and reliable measure of microbial contamination than ATP bioluminescence, the test enrichment period can be shorter and the overall timeto- result will be faster. As previously described, ATP bioluminescence reduces time-to-result from three to seven days to 24-48 hours compared to traditional microbiological methods. The use of AK technology reduces the time-to-result to 18-24 hours, an additional 25-50% reduction from the already rapid ATP bioluminescence method. Major personal care companies have recognised that if fast is good, faster is better still. These manufacturers have made the decision to further streamline their lead times and productivity by moving from Celsis ATP bioluminescence technology to Celsis AKuScreen for their product screening.
Quantifying the financial Benefits
The financial benefits of implementing the Celsis rapid detection system were studied by management consultant, Arthur D. Little (ADL) on behalf of a major personal care manufacturer before the company implemented the system globally. The study concluded that adopting the technology for a single product in a single plant would realise a five year net present value of nearly $1 million6 and a payback of less than six months. ADL projected that implementing Celsis technology in all the company’s 70 facilities would yield financial benefits in excess of $55 million over the first five years of the project.
The savings calculated by ADL considered only the redeployment of working capital invested in microquarantined inventory. As companies have moved to rapid microbial testing methods, additional savings derived from the more effective management of contamination events and the reduction of manufacturing lead times have been apparent and can also be quantified.
Choosing a partner for rapid methods
Successful implementation of rapid methods goes beyond good technology. In addition to high quality, sensitive reagents, reliable and robust instrumentation and software, manufacturers need a partner with the experience, resources and commitment to enable them to realise the full benefits of the technology. Celsis provides unparalleled support by combining our application and implementation experience with a strong infrastructure of technical support.
As elsewhere in the world, Celsis has built a network of experienced and certified distributors across the Asia Pacific region that provide local reagent supply, service maintenance, and technical support to global and local personal care product manufacturers. In addition, Celsis has regional technical support to provide on-site installation and validation support up to the point of initiating parallel testing. Regional support is delivered in concert with local support, ensuring that the customer is well on the road to rapidly releasing products shortly after installation.
Personal care manufacturers in the Asia Pacific region attest to the value of Celsis technology and support as the use of the technology has grown steadily with major installations in virtually every country in the region.
The future
The reduction in microbial testing times from three to seven days to 18-24 hours creates tremendous value for personal care manufacturers measured in terms of reduced working capital requirements and the more effective management of contamination risks. Given the clear and quantifiable benefits of achieving faster results, the next step must be to reduce testing times even further. Results in eight hours would allow for same-shift test and release procedures, further streamlining manufacturing and enhancing response times. Ultimately, the goal of detecting and identifying microorganisms in real time will be achieved.
Celsis continues to invest in research and development towards the achievement of these goals.
As technology and the ongoing pressure for efficient manufacturing converge, we can expect to see rapid microbial methods positively impacting the personal care industry for years to come.
References
1 Deloitte & Touche LLP, Mastering complexity in global manufacturing. Powering profits and growth through value chain synchronization, www.deloitte.co.uk (2003).
2 Anderson D., Copacino W., Lee H., Starr E. Creating and Sustaining the High-Performance Business: Research and Insights on the Role of Supply Chain Mastery, www.accenture.com (2003).
3 Adenylate kinase technology is exclusively licensed to Celsis International Plc by the UK Department of Defense and Scientific Testing Laboratories (Dstl) for use in the personal care, pharmaceutical and beverage industries.
4 Pimsner M. Emerging Technology Assessment: Leveraging the power of adenylate kinase for rapid microbial testing, www.celsis.com (2005).
5 Meighan P., Nelson D., Layte K., Foote N. Rapid and Reliable Detection of Molds within 24 hours, Poster No. Q 037, American Society of Microbiology Conference (1997), Excerpt at www.celsis.com 6 Five year Net Present Value is defined as the projected cost savings for the first five years post-implementation discounted to reflect their value in today’s dollars.
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