June 15, 2008 (Vol. 28, No. 12)

Quality, Innovation, and Speed Remain Critically Important Skills

As the recent “2008 Biopharma Outsourcing” conference sponsored by iiBIG underscored, the term contract research organization (CRO) can take on a wide variety of meanings depending on the specific company it’s applied to. As the conference also reinforced, though, there are certain metrics that apply virtually across the board.

Judith Gwathmey, M.D., founder, president, and CSO of Gwathmey (www.gwthmey.com), summarized several of them in her presentation to the group: flexibility, good communication, affinity for the client’s science (as opposed to a commodity approach), and a stable team that is on top of their skill set.

Started on the Harvard Quad in 1994, Dr. Gwathmey’s company now employs 17 people at its laboratories in Cambridge, MA. “A preclinical CRO should live and breathe the client’s science,” she stated, “matching up with them strength to strength. It can’t be a commodity-based business.” And because drug discovery and development is a highly fluid process, Dr. Gwathmey stressed that the CRO has to be flexible in its project-management approach in respect to timing and changing parameters on short notice.

“We have to think and work with our clients and then bridge them to the next partner—not just toss them over the wall,” she added. Her organization stresses providing “a stable team that stays with the client’s study.” Experience and cross-training equip Gwathmey to look for things that may not be in the clinical protocol—changes in respiration or eating habits, for example, that may indicate an animal is not in good shape and would not provide a valid picture of a drug’s effect.

“We ran a trial where the first two rats that were dosed convulsed and died. We lowered the dose and tried again with the same result. A bad formulation was at fault. By proceeding the way we did, we prevented any unnecessary loss of time and resources,” Dr. Gwathmey noted.

The term “commodity” as it applies to the services provided by CROs is something big pharma seems to be pushing, according to Peter Pekos, president and CEO of Dalton Pharma Services (www.dalton.com). Pekos referred to it as the “Wal-Martization” of a function he views as anything but that.

Managing Complexity

“The challenge everyone faces is managing the complexity of the drug-development process,” he said. Pekos pointed out the advantages of working with a CRO that can match up both capabilities and important intangibles with the organizations they are trying to serve. “We tend to focus on North America with the U.S. being our largest market. We speak the same language and abide by the same rule of law,” he noted.

Another aspect is harmonization, Pekos added, currently a fact of life between Canada and the EU, but a work in progress in terms of the ICH and FDA. “Clearly,” he stated, “for the industry to move forward a more efficient process of harmonization is necessary.”

For those who think they can save money by moving work offshore, Pekos suggested otherwise. “There isn’t likely to be much impact on total costs,” he said, “when you factor in the time it takes to fill in holes and gaps created by miscommunication.” In addition, he noted, China and India will soon be providing drugs to their own populations, as India is doing now via generics. “Going offshore may buy five to 10 years of savings but at what long-term cost?” Pekos wondered.

Judd Berman, cofounder of Dalton Medicinal Chemistry, the medicinal chemistry arm of Dalton Pharma Services, said that quality, innovation, and speed are the hallmarks of the company’s team of experienced medicinal chemists. “We want long-term relationships with a limited number of select partners who are interested in investing in the person-year time domain, not person-week,” he stated.

Dalton provides chemistry from lead identification and optimization through GLP and GMP for clinical development and on to commercialization. “Many of our customers want several steps done by the same source to prevent extra handoffs, which can cost time and lead to mistakes,” Pekos observed.

David Phillips, senior vp, sales and marketing, at BioFocus DPI (www.biofocus.com), agreed that time is indeed of the essence. A Galapagos company, BioFocus concentrates on target discovery, HTS, and lead optimization in its preclinical collaborations. Speed, at the end of the day, is “the over-riding metric,” Phillips said.

Outsourcing is growing 10% to 20% per year, he observed, while international pharma is not building infrastructure. “They’re not adding buildings or people anymore,” he noted. “The fact is, the top four pharmas place work in India and China and with BioFocus DPI. The difference is that our programs use 20-year medicinal chemistry veterans across the disciplines that comprise a highly experienced team. In addition, we do ADME in silico and in vitro under one roof in a fully integrated drug discovery program. India and China are less likely to assemble integrated teams with similar experience. When you are conducting a program and want lead optimization fast, you don’t want to rely on a source that can slow down the process.”

Extension of Client’s Development Group

Janet Wolfe, Ph.D., president of Wolfe Laboratories (www.wolfelabs.com), told the conference that a good CRO should act as an extension of the client’s development group and spoke up on behalf of doing business locally where expertise, ease of communication, and shared language and culture are most easily found.

“Communication is important,” she stated. “Fifty percent of our clients are within a 25-mile radius. They value face-to-face interaction. Teleconferences and e-mails frequently don’t capture the essence.

“With the 50 percent of our business that is not local, we make a concerted effort to set up regular meetings. We return phone calls and e-mails the same day because no response indicates there may be a problem. And we have a regular schedule for sending updates so that management and investors have the data they need to make their jobs easier.”

Wolfe Laboratories is what its president calls “a bootstrap operation,” founded nine years ago without any outside investors. She described her company as a niche organization serving “one-compound companies,” mostly in the Boston area. “I focus on biotechs and pharmas that have raised at least $15 million in venture capital,” she said. “When a molecule is nominated we take it all the way to Phase I, with involvement in critical path activities.” Dr. Wolfe cited lead optimization, ADME, toxicity studies, route of administration, dosage schedule, GLP, and GMP as areas where Wolfe Laboratories offers cost-effective services.

“Our services are customized for every compound, which may seem like it would be more expensive, but we think our costs are lower overall.”

Cambridge Biomedical Research Group (CBRG; www.cambridgebiomedical.com) provides clinical trial assays based on a platform of broad scientific experience that translates into rapid project completion, according to Al Correia, CBRG vp, operations. “When you look at clinical trials, every one is an entity unto itself with unique opportunities and challenges,” Correia said. “You have to be flexible in your approach—plan, plan, plan, and then be ready to change.” In his experience, there are too many instances where a bias or specialization drives the decision, versus the technology being chosen that best suits the project needs.

The decision may not be as straightforward as it first appears. Correia cited one case where the technology default was HPLC, which successfully isolated a number of metabolites. But the physicians wanted only the biologically active ones, so CBRG went back to a bioassay. In another instance, company analysts found areas in a Phase IV study that could be improved, but revalidation and resubmission ruled out making the change even at triple the productivity.

Expanding Services

As clinical trials become increasingly worldwide, Global CINRG (www.globalcinrg.com), led by CEO Ahsan Awan, entered into a collaborative agreement in 2002 with PharmalinkFHI, a full-service eClinical CRO, to strengthen its role as a site-management organization/CRO.

“Our original focus was managing global cardiovascular and metabolic trials,” Awan said. “As a result of being involved in protocol designs and other pretrial strategic development meetings, we were involved in discussions long before vendor selection. Sponsors would ask, ‘Who should we partner with?’ We would say, ‘Whoever you want.’ This proved not to be a good answer, because CROs saw it as revenue loss to have us involved. So in 2000 we expanded into CRO activities and two years later partnered with PharmalinkFHI.”

CINRG (pronounced synergy) has been embracing the digital frontier in managing global clinical trials in more than 70 countries to date and hopes to increase that number in the next year by expanding its research network and recruiting additional national directors.

“We currently run three database applications that were built in-house: ISIS™—our patient screening and investigator and site-selection tool; GlobalSearch™—our flexible, multivariable search engine; and REDbase™—our research EMR platform,” Awan stated, “with metrics established from site to site and country to country that validate the effectiveness of our tools individually and as a comprehensive suite.

“It is our mission to operate faster, more efficiently, more accurately, and more effectively than our competitors, with the goal of lowering the cost of development and increasing ROI by addressing the pain points that delay approval, rollout, and the ability to turn over new and existing assets in order to generate revenue.”

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