REGULATORY CHALLENGES

BioPharm: In your company's experience, how can a CRO best plan to meet regulatory and sponsor expectations for biologics development and testing?

Gillett (Charles River): The important message for all biologics developers is that there isn't one plan that all biological products can follow. Some programs, such as those involving embryonic stem cells, are extensive and require tumorigenicity testing, while other programs can be based on purely in-vitro data. Each program needs to verify that the drug can produce and retain exposure and effects, and that studies gauge the doses where effects turn harmful.

Greer (SGS): To assist clients in meeting analytical challenges, a CRO should be fully aware of the complexity of task. It should be sensitive to expectations of regulatory authorities and have an arsenal of appropriate analytical methods, assays, and clinical-trial techniques that are capable of providing reliable scientific data so that informed decisions can be made regarding product safety and quality.

SPONSOR EXPECTATIONS

BioPharm: How have sponsor companies' expectations for biopharmaceutical contract R&D and testing changed over the past few years? What do you think has led to these changes?

Gillett (Charles River): In the past, biologics were developed by mid-sized pharmaceutical firms. Increasingly, we're seeing small virtual firms, or nascent biotech companies, assuming sponsorship and taking compounds from early stages into Phase I and II clinical trials. Additionally, more sponsors are risk-sharing by partnering early in development. In these cases, collaborations can involve multiple consultants, teleconferences, and web meetings. It's especially important to establish communication and primary contacts to ensure a solid and confidential connection. At Charles River, we have increased our support for these companies and find the experience is rewarding on both sides because we learn from each other and bridge gaps that start closer to compound discovery. For example, we often suggest the experiments that sponsors start in university labs, and then transfer the technology to good laboratory practice (GLP) settings when product quality and biomarkers are established.

The models of development need to shift as well to accommodate changes in public policy, regulatory law, international outsourcing of chemical manufacturing—all of which impact costs. Biopharmaceutics are combining genetic, cellular, device, and nanotechnology. These new approaches require access to specialized facilities and expertise. Although traditional models are in place for Big Pharma, they are shifting to more open collaborations as well.

Kauffman (Lancaster Labs): Sponsors are looking for partners to help get their products to the market faster in an environment where regulations are becoming more stringent. At Lancaster Laboratories, many clients are looking to compress timelines and accelerate speed to market. Development of biologics is extremely expensive, so sponsor companies are also looking to consolidate vendors and reduce costs.

Breau (MPI): In the past, most pharmaceutical companies kept preclinical functions, such as assay development, initial GLP studies, and first-in-man human pharmacokinetic analyses in-house, to control these critical components of the development process. Today, many companies have downsized their preclinical departments and rely more on CROs for an ever-increasing array of services.

In addition, there is increased emphasis on in-licensing from biotechnology companies. Rather than rely on in-house discovery, large pharmaceutical companies have increased the proportion of sponsors in early development that are small biotech or virtual start-up companies. The biotech companies rely on quality CROs to provide input into their study designs and development plans. This shift has led CROs to provide more service offerings, including an expansion of program-management services.

Greer (SGS): Our experience at SGS Life Science Services is that sponsors are not just looking for tests to be performed and data returned. They are actively searching for companies with appropriate experience who can guide and advise them during the analytical program. This consultancy might take the form of recommending and providing certain analytical packages or groups of tests for particular types of products.

Although sponsors are now used to the 'one-stop-shop' concept, their expectations have grown. Sponsors want to establish that the CRO has in-depth expertise and crucial techniques. New emphasis from regulatory agencies to obtain data using orthogonal techniques and to mitigate potential biases from particular methods are also changing the way sponsor companies use CROs.