A Precursor to Approval
The preclinical development process gauges the capabilities, limitations and possible dangers of drugs and drug ingredients before they are tested on humans. The preclinical process is an undertaking that is not only expensive, but also risky. Although all pharmaceutical companies hope that their product will excel during the preclinical process, many never advance to the clinical stage.
Considering the risks involved in the preclinical process, it is understandable that companies attempt to put their products in the hands of highly knowledgeable preclinical specialists. When these specialists cannot be found in-house, some companies find that contract service providers offer a valuable solution. Contract research organizations (CROs) offer a wide variety of preclinical services, with specific areas of development devoted solely to subjects such as active pharmaceutical ingredients (APIs), parenterals and other subsets. To find out more about preclinical service providers’ offerings and current trends in preclinical development, Pharmaceutical Processing spoke with three preclinical service companies which each offer unique services.
Choosing a Service Provider
What leads manufacturers to enlist the help of a preclinical service provider? Although the reasons will invariably differ from company to company, some motives are more common than others.
According to Prasad Raje, President of Smithers Pharma Services LLC — a company that offers pre-formulation and formulation services, analytical chemistry, preclinical and clinical bioanalytical testing and in-house storage stability studies — the pharmaceutical company’s size can be a factor. “Large pharma is going to outsource for capacity issues,” while for the smaller, venture-funded companies, “it’s just a matter of if they have in-house capabilities or not. Many just don’t have those [capabilities], and choose to go down the route of getting work done through CROs.”
“Pharma is restructuring to address its patent cliff and lack of new approvals to focus on what it believes to be its core competencies. As such, most large pharma organizations are outsourcing a substantial portion of their preclinical and clinical development for their APIs,” explains Geoff Evans, Vice President of Business Operations at Alphora Research Inc., a company that provides API technology development services for the scale-up of complex small molecules. “Where this outsourcing was once tactical (follow a set procedure), it is increasingly strategic (leave it to the CRO to define the process).” The industry is drawing inspiration from other sectors: “In this respect, the pharma industry is moving increasingly to the virtual development model already employed within the biotech sector.” Some companies may decide to enlist help for very precise processes, as well. One such process is 505(b)(2).
“One of the things that’s really important in the development of these kinds of products is the correct choice of studies,” explains Kenneth Phelps, President and CEO at Camargo Pharmaceutical Services, a company that provides end-to-end drug development through the 505(b)(2) process. “In the 505(b)(2) space, there really isn’t a roadmap for people to understand which studies should be run … so most of our clients come to us because they really don’t know what studies need to be done and how those studies need to be designed.”
Increasing Approvals, Hastening Timelines
Time is money in the pharmaceutical industry. Some companies find that hiring a contract service provider pays off in the long run, as it can sometimes shorten research and testing times.
“Sometimes we’re able to focus in on just the things that are necessary to be done for the purpose of getting [the product] into human studies,” explains Phelps. Although “It’s widely known that for brand-new drugs, there’s a huge attrition at the junction between preclinical and clinical,” Phelps explains that Camargo has achieved excellent results in the past: “In the nine-plus years we’ve been in this business, and the dozens and dozens of preclinical studies that we have done, we have not had one single failure — everything we’ve done in preclinical has moved on to clinical work.”
Phelps explains that “(b)(2) is not so much about science risk; it’s mostly about execution risk. Whereas with new drugs, it is primarily about science risk — you never know what’s going to happen.” For that reason, having specialists onboard who know the particulars of the process — whether it is (b)(2) or another specialized process — can be beneficial for many companies.
Adjusting to Modern Approaches & Industry Growth
Phelps observes that preclinical requirements are currently increasing, and one notable factor in this increase is that most drugs are developed for an adult population. Around “75 percent of the drugs prescribed today do not have adequate information for children,” but to increase safety, Congress has recently made amendments which strengthen the Pediatric Research Equity Act (PREA). According to Phelps, this increased scrutiny is “forcing pharmaceutical companies to develop child-friendly formulations.” In 505(b)(2), “we always have to consider that these drugs that were previously made for adults, and we now need to make sure that they are suitable for children.”
Other preclinical services are evolving, as well. Evans explains that API development is not exempt from these changes: “The current trend is to conduct only limited development on the API process during the preclinical to Phase I stage,” he says. “This reflects the realities of the patent cliff, pipeline attrition rate and reduced research budgets in both pharma and biotech.” According to Evans, “From a business perspective, this approach has merit. However, if a Phase I is successful, there is considerable pressure to address the process deficiencies, and in a hurry. In essence, the process development that once occurred for Phase I has now shifted to Phase II.” To adjust to these changes, “Alphora’s business is increasingly focused on improving processes in Phase II, addressing the process and analytical deficiencies to make an economically and regulatory viable process.”
Raje says that Boston-based Smithers Pharma Services is seeing regional growth. “Because of venture funding in Boston — Boston area has seen the most funding in the nation last year and the trend has continued in 2012 — we see growth of small and medium biotech companies. These companies don’t have all of the preclinical segments in their house to support drug development, and that has continued to lend us more work.”
A New Phase
The pharmaceutical industry has seen a number of recent changes, and preclinical service providers will need to evolve in order to meet clients’ new needs. The experts note that CROs will likely evolve not only by expanding services that are in high demand, but also by selectively consolidating other services.
Phelps believes that consolidation will impact the future of preclinical development. “On the side of the providers, the CROs, you’re going to see continued consolidation. There have been too many preclinical providers … I think you’re going to see a greater tendency to use these high-throughput models to try to improve the outcomes, in other words to reduce the attrition from preclinical to clinical.”
In such a versatile marketplace, Raje sees pharmaceutical companies looking for more versatile CROs in order to help simplify their processes. “I see these companies running thin on project management, so they are not truly enamored by having to place work at four or five CROs,” he says. “Smaller companies are looking for more of a service continuum.”