Contract research organizations (CROs) have been growing at an impressive clip since the 1990s, when the R&D efforts and needs of pharmaceutical companies started becoming increasingly more complex. Despite their ongoing focus on innovation, most pharmaceutical companies, regardless of size, have also had to bear the weight of increasing external cost pressures, which have contributed to a downsizing trend over the past five years. CROs have had to step in, not only to allow companies to expand their R&D efforts beyond their in-house capabilities, but also to patch up gaps in competencies.
Indeed, CROs provide substantial global capacities to drug developers and have become critical contributors to clinical trials activity. According to a 2009 study conducted by Business Insights, an independent market research firm, clinical trials conducted by CROs are completed up to 30 percent more quickly than those conducted in-house by pharmaceutical companies. The study notes that two years ago, the total CRO market size was estimated at $20 billion, and is expected to grow at an annual rate of 8.5 percent, reaching $35 billion in 2015. These kinds of predictions reflect the ongoing growth opportunities for CROs, especially in the current economic climate. However, with more players entering the field, regulatory standards are bound to become more stringent worldwide. Successful CROs will be measured not by the amount of business they conduct, but by the quality assurance of their results.
XenoTech LLC—a Kansas-based CRO founded in 1994 that offers drug inhibition, enzyme induction and drug metabolism studies for pharmaceutical, chemical, food, academic and regulatory organizations in the United States, Japan and Europe—realized the importance of quality assurance in its lab early on. Most of the studies performed by the company are governed by good laboratory practices (GLP) standards to ensure data quality. For XenoTech, a high standard of data quality translated into, among other things, the regular verification of its automated liquid-handling equipment. According to Steve Otradovec, XenoTech’s lab automation senior scientist, the lab’s automated liquid handlers are used primarily for sample preparation and incubation— the bulk of XenoTech’s work.
“After purchasing our first liquid handler, we decided to verify it monthly—at a minimum—to maintain consistency with our verification standards for our manual pipettors,” explains Otradovec. “At that point in time—this was about six years ago—it seemed like most liquid-handling companies dismissed the need for routine verification, insisting that annual verification was sufficient. At XenoTech, we constantly strive to perform our work at the highest standards of quality, and this demands a trustworthy assurance that our equipment is operating effectively. We can’t put faith in mechanical equipment; we need evidence. We’re also highly SOP driven, and our robust SOP requires monthly validation of this equipment.”
In 2006, XenoTech verified its liquid handlers gravimetrically using balances. Each liquid-handling robot took four hours to validate.
“We knew that if we added more automated liquid handlers, we’d practically have to hire someone full-time to verify them,” adds Otradovec. “That’s what drove us to find another method.”
As XenoTech set out to find alternatives that would minimize the time it took to validate its automated liquid handlers, it began to experiment with developing an inhouse spectrophotometric method. As XenoTech strove to replace gravimetry in its lab, the company learned about Artel.
Based in Westbrook, ME, Artel has pioneered liquidhandling quality assurance worldwide. The Artel multichannel verification system (MVS) uses dual-dye ratiometric photometry to assess the precision (the repeatability of volume transfer) and accuracy (the closeness of the transferred volume to the target volume) for each tip of almost any multichannel pipetting device at volumes as low as 10 nl. Because measurement results are NIST-traceable, the MVS allows for the direct comparison and measurement consistency between operators, methods and liquid handlers—regardless of make, model, manufacturer or location.
“When we heard about Artel, we realized that the MVS would allow us to do exactly what we’d been trying to do and more,” says Kammie Settle, marketing manager at XenoTech. “We’re dispensing such low volumes, and everything has to be very accurate and precise to be repeatable and robust. Because we offer GLP contract services, we put a lot of emphasis on repeatable data. Samples have to be within a certain range. The more accurate our incubations are, the better our data is— we don’t like to do repeat tests that use our time and resources ineffectively.”
Keith Albert, Ph.D, Artel’s technical marketing manager, arrived at XenoTech with the MVS, and proceeded to do an installation and operational qualification onsite. To Otradovec’s delight, Albert completed the installation in less than two days, and proceeded to conduct a handson training for all technical staff.
Since Albert’s visit in 2006, XenoTech went on to acquire additional automated liquid handlers to manage the increasing workflow. As the company used the MVS, the time it took to accurately verify each robot was slashed significantly—from four hours down to 15 minutes.
Having experienced such dramatic time savings with its liquid-handler verifications, the company started using the MVS to troubleshoot new scripts. According to Otradovec, XenoTech’s use of the MVS goes beyond equipment verification, since the system is able to mimic what a new script does to ensure that it’s working correctly. For instance, when XenoTech builds a script for its automated liquid handlers, it can use the MVS to make sure that specific target volumes within different automated scripts are transferred with accuracy and precision, before implementing them.
Another time-saving benefit of the MVS for XenoTech has been the MVS’ ability to troubleshoot the company’s liquid-handling robots. “When we want to troubleshoot a liquid delivery, we can use the typical automation interface and deck setup without the need to rearrange the deck for a gravimetric balance or an alternative software program,” explains Otradovec. “The ability to test in real mode has enabled us to find liquid-handler hardware problems that would have been unidentifiable using alternative gravimetric methods.”
A booming future and time to invest in it
Twenty years ago, both the role model and business model for CROs used to be simple. Pharmaceutical companies were in charge of developing a new drug and taking it through clinical trials, and CROs handled outsourced work for the drug company, staffing a trial or analyzing the data produced in the study. However, with competition, financial pressures and looming patent expirations battering the pharmaceutical industry, drug companies are continuing to turn to outsourcing as a principal component of their new business models. While this has led to CRO growth, it’s also leading companies like XenoTech to provide more than just outsourced work.
“Our services go way beyond screening,” notes Settle. “We specialize in regulatory submission studies, and provide our customers with enough information, going beyond mere technical data, so that they can make an informed decision about whether they should move forward with a compound’s development, and then what that next move might be.”
Many of the studies performed by XenoTech revolve around in vitro enzyme induction studies in human hepatocytes, which are conducted in accordance with FDA recommendations. The company’s process involves treating cultured hepatocytes from three human livers for three consecutive days with three or more concentrations of drug candidates. These studies, among other studies conducted at XenoTech, have the important task of predicting the metabolic pathways in humans years before human clinical trials are approved, and can also be used to predict dangerous drug-to-drug interactions. This is no small feat, and quality assurance and control play an integral role in achieving it. By bringing the Artel MVS into its lab, and with its current population of liquid handlers, XenoTech has added 336 hours per month to the time it can spend focusing on developing groundbreaking studies that can help drug companies bring safer drugs to market faster.
XenoTech, based in Lenexa, KS, is a contract research organization with expertise in evaluating drug candidates such as substrates, inhibitors and inducers of cytochrome P450 enzymes. For more information, please email firstname.lastname@example.org or go to the company’s website at www.xenotechllc.com.
Artel is a worldwide leader in liquid-handling quality assurance. Artel’s accurate and easy-to-use systems ensure data integrity in any process requiring liquid volume measurement. For more information, contact Artel at 207-854-0860 or go to their website at www.artel-usa.com.