Contamination in pharmaceutical products makes headlines, creates potential nightmares for drug manufacturers, and shakes the confidence of patients, physicians and regulatory authorities. Contamination causes a ripple effect that magnifies costs exponentially the further from the source it is detected. Yet for many pharmaceutical development and manufacturing companies, traditional testing methods are so slow and the pressures to release products to market are so strong, that there's often a potentially dangerous balancing act playing out between recall risk and supply chain efficiencies.
Fortunately, newer rapid screening methods for contamination are available to safeguard patients, reduce risk, and decrease manufacturing cycle times for a leaner and more responsive supply stream. Because pharmaceutical manufacturers are highly regulated, prescription drug companies are required to test their goods for the presence of bacteria, yeast or mold prior to releasing product to market. From the supply chain management perspective, however, this comes at an enormous cost.
At every stage where microbial testing is done — in raw materials, work in process or finished goods — each batch is held in quarantine for an average of five days before it is pronounced ready to advance. This ties up working capital and incurs storage expenses, explaining why, if a company's products are "clean" 98-99 percent of the time, there is a significant temptation for drug manufacturers to release products without holding them quarantined. In today's competitive global marketplace, escalating pressures to manufacture pharmaceutical products faster and for less money, without sacrificing quality, can magnify the risk of contamination.
Faced with the challenge of balancing demanding customer expectations with profitability, forward-thinking pharmaceutical companies are increasingly adopting rapid microbial detection methods. Simply stated, the faster drug manufacturers can identify a contamination and implement corrective actions, the more successfully they can minimize costs and avoid potential product recalls that can pose a human health risk.
Today's newest rapid microbiological testing methods (RMM) reduce time-to-results 80 percent faster, from the five day average to just one day, helping drug companies to contain outbreaks, streamline operations, and capitalize on process improvement in their manufacturing cycle.
Cut Production Time with Advanced RMM Solutions
Microbial testing is a critical but classically time-consuming phase of the manufacturing process. A majority of pharmaceutical companies continue to rely on inefficient agar plate growth methods that remain essentially unchanged since their widespread adoption in the 1800s. Each time a product batch is tested, this traditional method requires from three to seven days or more, depending on target organisms, before results are available. Assuming testing is conducted on raw materials and finished products, that means anywhere from six days to two weeks are needed for the microbial testing process, and even more time is required if in-process or sterility testing is performed.
During this period, full lots of raw materials or finished goods are frequently quarantined in micro-hold – even as additional inventory continues to be produced. Since products are typically not released for distribution until they are determined to be contamination-free, inventory costs add up while sales revenue is delayed. The longer products sit idle in micro-hold, the more they cost the manufacturer in lost revenue.
By utilizing newer enzyme and molecular-based technologies that significantly compress testing times, RMM solutions can dramatically slash the amount of time products must be held in micro-hold and drive new efficiencies throughout the supply chain. Easy-to-use, reliable bioluminescence-based systems with ATP (adenosine triphosphate) yield definitive results within 24-48 hours, while even more sensitive AK (adenylate kinase)-enhanced bioluminescence assays are accurate and reliable within 18-24 hours. Because these methods rely on amplifying the growth of micro-organisms for fast detection, their protocol is the most similar to classical growth-based methods, making validation and regulatory submissions easier and simpler than other types of RMMs.
For process manufacturers that invest millions of dollars in initiatives designed to shave minutes off the manufacturing process and streamline the flow of goods through the supply chain, the value of shortening micro testing time by several days or weeks can be monumental.
Achieve Significant Savings with Rapid Detection
Reducing the time materials and products spend in quality assurance testing leads to a better utilization of working capital for a number of reasons. Since fewer days are required to produce the same amount of product, goods are released to distribution faster and sales revenue can be realized more quickly. The shorter manufacturing cycle reduces the amount of product quarantined in micro-hold in addition to minimizing safety stock requirements. As a result, less capital is tied up in finished goods inventory and less warehouse space is required for storage. Pharmaceutical companies not only boost operational efficiency and lower manufacturing costs – they are also better able to meet the demands of lean manufacturing and Six Sigma initiatives.
Minimize the Costly Consequences of Contamination
Although a controlled manufacturing environment will produce 98-99 percent contamination-free products, drug manufacturers must be prepared to deal with potential contaminations. The ability to identify and isolate contamination as quickly as possible when it does occur enables companies to initiate corrective action sooner. This helps to minimize the impact of contamination on patient safety, as well as the negative consequences on the manufacturer's reputation or revenue. Clearly, the faster manufacturers can produce, test and release safe products following a contamination occurrence, the better for their bottom line – and their image in the marketplace.
Corrective action can be expensive and time-consuming. The contaminated product must be discarded or reprocessed and recovery is further delayed by the micro-hold required on the replacement product, which must be retested. Therefore, the value of using RMM becomes even more evident in the face of contamination. RMM solutions double a company's savings by slashing the time required for both the initial screening and the testing of the replacement batch to a small fraction of what was needed when traditional methods were used. [Fig. 1: Timeline]
With testing results available within hours instead of days, the amount of product that needs to be scrapped can be significantly reduced and, if a drug recall is necessary, it can be initiated – and ended – sooner. Even better, if the contamination is discovered quickly enough, the product never gets into the customers' hands, avoiding the need for a recall altogether and further minimizing waste.
RMM solutions not only accelerate recovery time, but also can play a valuable role in building physician and patient trust in the continued quality and safety of a company's pharmaceutical products. For example, while implementing RMM, one drug manufacturer chose to calibrate its AK-based testing method to be more sensitive than the microbial detection standards required by its FDA submission in order to minimize downstream risk. This voluntary decision bolstered internal confidence in the efficacy of its testing procedures and consumer confidence in the safety of its products.
Deliver More Rapid ROI with RMM
In conjunction with a global consumer products company, Arthur D. Little management consultants and Celsis, Inc., developed a financial model to quantify the value of implementing rapid detection methods. The model calculates the annualized containment savings, five-year net present value (NPV) and payback period using a company's own manufacturing and testing data. [Fig. 2 ROI graph] Although results vary depending on company specifics such as the cost of capital and frequency of contamination events, a typical single plant operation will achieve payback of its initial investment in six to nine months with a five-year NPV of approximately $500,000 to $750,000. And for a manufacturer that implements RMM across multiple plants, the savings can multiply quickly.
Redefine Quality Control Best Practices
Reducing by more than half the waiting time for contamination testing results, RMM solutions define a new "best practice" for pharmaceutical manufacturers who seek cost-effective approaches to boost supply chain efficiency and to reinforce overall confidence in company responsiveness.
Already accepted by global regulatory bodies including the FDA, RMM technology also supports efforts to achieve certification with ISO 9001 standards, cGMP compliance and other manufacturing best practices. Yet, it has been estimated that fewer than one in four pharmaceutical manufacturers are using rapid microbial methods. The companies that have demonstrated leadership in the adoption of this innovative technology have solidified their competitive advantage by streamlining their operations, enhancing their ability to quickly contain contaminations, and strengthening regulatory and public confidence in the quality and safety of their released products. The fast payback and long-term cash advantages make RMM a good investment in today's economy.
About the Author Cindy Lieberman joined Celsis Rapid Detection in 2007 as a vice president. She brings significant manufacturing supply chain, technology and healthcare industry experience to the role from her previous positions, most recently with Zebra Technologies. She is a graduate of Northwestern University in Evanston, Illinois. Cindy can be reached at 312-476-1200 or firstname.lastname@example.org.