By John Russell
April 14, 2010 | It’s estimated that perhaps half of all drugs brought to market by major biopharmaceutical companies are actually discovered by small-to-midsize players. Working behind scenes to help the latter companies move their molecules forward is small army of consultancies who provide needed expertise or capacity. Indeed, every Big Pharma layoff adds to their ranks.
For the successful ones, such as R&D Services Pharma Consulting, founded by Thomas Thompson in 2003, there are at least two keys growing a business: one is possessing a desirable expertise – in this instance drug metabolism and pharmacokinetics (DMPK); the second is being nimble enough to identify emerging needs and to expand your skill set to meet the need – he is currently writing a chapter* on the emerging role of drug transporters in clinical drug disposition and drug interactions, and expects some of the information to be incorporated into the next iteration of FDA’s guidance on drug interactions.
Indeed, RDS’s path to success has been prototypical. Trained (Ph.D.) in medicinal chemistry and toxicology (post-doc), Thompson worked on drug metabolism for 16 years for two companies (Hoechst Marion Roussel and Ciba-Geigy) and then for four years with CRO Quintiles (senior director and group leader, ADME/Drug Metabolism), which acquired his division of HMR.
Thompson says candidly, “Jobs were migrating out of the midwest to the east or west coast, wherever pharmaceutical companies were. My choice was either to move, which I didn’t want to do, or try this consulting business. My expertise is drug metabolism and pharmacokinetics and I had an intuition that that was a very marketable niche.”
It didn’t hurt that DMPK expertise was in relatively short supply among smaller biotechs and midsize pharma. “My typical client company is a small drug discovery company – they are medicinal chemists and pharmacologists and are really smart. They know a fair amount about ADME because they need to design that into their molecule. But typically they haven’t really carried the ball into development and are less familiar with the development activities that are pretty much prescribed by the FDA as a roadmap to get from the bench into clinical development.”
Some of RDS services include:
• Planning of critical in vitro and in vivo preclinical PK studies
• Preclinical and clinical PK data analysis with GLP- and GCP-compliant software system
• Use of preclinical PK data to model human exposure
• Use of PK/PD modeling to relate exposure to efficacy
• Integration of preclinical efficacy, safety and PK data to help estimate of FIH dosing
A measure of the importance DMPK assessment was highlighted in 1991, Thompson says, when “an industry survey** indicated the single leading cause of failure for drugs in clinical development was ‘poor pharmacokinetic or biopharmaceutic properties’, accounting for 40% of drug failures. Since that time, large pharma has taken elaborate and expensive steps to address this problem so that in a later survey***, the attrition rate for this reason dropped to <10%.”
PK problems haven’t gone away, he says, rather large pharmas have adopted a strict regimen of “best practices” for drug development which can cut the risk. Many smaller and some mid-size companies either don’t have the expertise, or if they do, their resources are stretched thin so that outside help such as RDS is necessary. Thompson characterizes this as translational development – helping clients move molecules from discovery into early clinical development, from “bench to bedside”.
RDS does no wet work. It mostly analyzes data (animal and human) and one of its primary tools is WinNonlin PK modeling software from Pharsight. About a year and a half ago, RDS had the software validated by an outside company so that RDS results could be accepted by FDA in submissions. That’s competitive advantage among DMPK consultants, he says.
RDS isn’t exactly a one-man shop. Thompson worked by himself “for the first several years and then probably about two or three years ago I saw an opportunity to spread out a little bit and try to market more by taking on some affiliate consultants,”.
Currently his affiliates include two pharmacokineticists, a bioanalytical chemist, and an expert report writer. “They are all, in one way or another, also consultants [and] we’ve kind of joined forces and when the need arises. I‘ll sub contract out pieces. One of my affiliates is a late stage clinical kineticist so hypothetically we could work all the way to NDA.”
Virtual teams are the wave of the future in consulting say many in the business, and perhaps on an even more widespread basis throughout industry. “In the future more independent workers will come together in virtual teams on an as-needed-basis for a given project and then disband when the project was over. Basically the only thing keeping this from happening faster is Healthcare benefits. If the employee paid for healthcare this trend would happen faster. We are becoming like sports free-agents moving from team to team,” says Stan Gloss, founding partner and managing director of BioTeam, a highly successful consulting organization specializing in IT, informatics, and cloud computing in the life sciences.
It’s hard to get a handle on exactly how many consultants service the biopharma world but it is clear their ranks are growing. Not surprisingly macro economic conditions can heat up or chill their business. “We were going great guns about until about a year and a half ago. I’ve compared notes with other CROs and consultants and they all pretty much say the same thing. The tail end of 2008 and most of 2009 were tough but the good news is that I see signs of life re-emerging.”
The downturn slowed the flow of capital into small biotechs, which in turn slowed their development programs. Thompson says he didn’t see that coming. Conversely, the current budget squeeze in mid-size and larger pharma is boosting their demand for outsourced services.
Thompson says, let me put it this way, “I do get a fair amount of business from midsize companies and precisely for that reason. They are under hiring constraints, or they’ve got a set staff and get slammed with an extra project. So I’ve had several assignments where I just kind of fill in and do some fairly routine report preparation or report review, not the most exciting stuff but certainly I welcome it.”
“One of the strategies I have undertaken to help generate new business is in addition to just looking for new clients I am also aligning with other contract labs and so my most recent assignment was doing a toxicokinetic analysis and report for a Midwest toxicology contract lab who doesn’t have their own kineticist on staff. So that’s a preclinical GLP type assignment. Before that I worked with another Midwestern statistics company and they had been engaged to provide a clinical data analysis and statistical data analysis for a bioequivalent study for a well-know generic drug company and I provided their pharmacokinetic analysis, again, that has got to be under good clinical practice so that validated software came in handy.”
Smaller companies understand the importance of DMPK work, says Thompson, but they are less advanced in their acceptance and use of pharmacodynamic (PD) models. “We’re sort of in the infancy of applying PD modeling. Academicians have done that for years and large pharma has done that for years but smaller companies are just now starting to think along those lines and consequently I am just starting to think along those lines. It’s a bit of the “Holy Grail” - to be able to not just collect animal data to predict what might be toxic levels but also to predict efficacious levels”
He says expertise in a particular therapeutics is rarely required in his work, though there are exceptions. For example in CNS work, it’s vital to understand transport across the blood brain barrier.
Long-term, he says, versatility is essential to thrive in the consulting environment. “When I entered the business seven years ago I was pretty focused on drug metabolism. As the business has evolved I had to evolve along with it and become more proficient in pharmacokinetics and more proficient in a lot of areas. For example, drug interactions are becoming a very strong piece of my business and the ability to forecast and test for the drug interactions. That’s a growing field.”
Likewise, “drug transporters are absolutely the hot topic fright now,” he says. “The FDA is more ahead on this issue than they were on Cytochrome P450s twenty some years ago. They don’t want to get caught this time so they are out front leading the charge on incorporating drug transporter information into the preclinical evaluation of new drugs. One of my current projects, that I am not getting paid for, is to write a chapter on that.”
Given the sea changes in the biopharmaceutical world and a seeming long-term shift towards more outsourcing, it will be interesting to watch how the consultant world serving life sciences evolves – whether by accretion among small organization which grow big or the proliferation of smaller practices and the rise of virtual teams, or both.
* Pharmacokinetics in Drug Development, P Bonate and D Howard eds, Springer, planned release late this year
**Kennedy, T., Managing the drug discovery/development interface, Drug Discovery Today, 1997; 2(10):436-444
***Kola l., Landis J., Can the pharmaceutical industry reduce attrition rates?, Nat Rev Drug Discov. 2004 Aug; 3(8):711-5