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Pre-Clinical Research in the Pharmaceutical Industry

Biological research scientists in pharmaceutical companies play major preclinical roles in two areas: discovery and development. The discovery phase may be described as performing directed and highly focused research to identify and validate a therapeutic target. The aim of this research is to identify molecules that modulate a target according to its therapeutic objective. The development phase is focused on identifying a compound that selectively modulates the function of the target that was identified in the discovery phase.

The nature of the research conducted at the discovery stage is very similar to the basic research at any NIH-funded institution. It utilizes all of the in vitro and in vivo biochemical, cell biological, molecular, genetic assays/approaches to identify a target, and to validate that target. The laboratory atmosphere resembles that of academia and includes independent technicians and postdocs as well as mentor/student relationships. Often, people who are not familiar with the pharmaceutical industry feel that industry scientists are forced to abandon the rewarding aspect of mentoring in their research career. In reality, most pharmaceutical companies have highly competitive summer intern and postdoctoral training programs. Another misconception regarding industry research is that conducting proprietary research and publishing in scientific journals are mutually exclusive. In fact, many companies have publication requirements and publication performance is an important component to being advanced to positions of greater responsibility and opportunity.

However, there are two important differences between conducting research in a pharmaceutical setting vs academics. First, the research is highly focused toward the endpoint of finding a target for drug development. It is imperative that the researcher maintains this approach by identifying and performing key validation experiments as quickly as possible. The challenge for the biological scientist is to design the experiment(s) to "kill" a target (demonstrate that it is not worth pursuing) rather than to fully characterize that target. The second difference is the enormity of the coordinated support facilities that exist in pharmaceutical companies. The number of personnel in a typical pharmaceutical research laboratory is small compared to its academic counterpart. However, utilizing the complimentary research groups with expertise in bioinformatics, proteomics, and genomics—not to mention the company's infrastructure to facilitate communication—the amount of information that can be generated and analyzed by these small research teams is staggering. Even with these notable differences, conducting research in an industry setting relies on the same principles as doing so in an NIH-funded lab: it is essential to plan and perform complete, thorough, and controlled experiments.

Once a target is validated, the program shifts from the discovery phase to the development phase. The biological scientist that identified the target maintains a leadership position in this aspect of drug development but is joined by additional scientists with specialized skills outside the biological arena. Such skills include chemistry, crystallography, chemical-screening sciences, and others who may have experiences relevant to the nature of the target (eg, lipids, enzymes, and structural proteins). In this phase, the biological scientist is prominent in the management of the project as it shifts from target identification/validation to completely different experimental paradigms. For example, the biological scientist may now be responsible for developing and adapting assays for a high throughput screening format that are amenable to examining hundreds of thousands of compounds. This involves not only assay design, but assay validation. Moreover, at this stage additional in vitro screens to validate "hits" (compounds with the desired effect on the target) are also designed and integrated to test for in vivo efficacy. At this stage, pharmacologists, drug safety and metabolism groups, and toxicology groups are brought into the project to apply their expertise to the goal of identifying compounds that will ultimately become medicines.

Successful management of these dynamic processes within the industry is absolutely critical to ensure an efficient and effective utilization of resources, both human and experimental, and to meet the tight timelines that are necessary for coordinated movement of products through the pipeline. As a particular project moves forward in the preclinical discovery and development phases, specific scientific teams are continually brought together to accomplish a task and then disbanded only to reform with a different composition for a different purpose. Scientists must learn to work in an ever-changing team environment, and communication of information is essential to ensure that the proper decision points are reached. As predicted, personnel and time-management skills are absolutely critical to success in an endeavor such as this. This takes several forms, which includes developing and implementing performance plans and integrating those plans with specific endpoint matrices that are developed by upper management. Remember, the ultimate goal is to develop safe and innovative products for the patient (customer) and to bring value to investors (shareholders).

As with academic research, research in the pharmaceutical industry is both challenging and prone to failure. The stakes are much higher and the margin of error is narrower. However, the satisfaction that comes in moving a concept to the clinic is enormous.

Footnotes

As the Trainee Page enters its second year of publication, we at the Journal want to remind you that the 30th Annual Meeting of the American Society of Andrology is going to be held at the Elliot Grand Hyatt in Seattle, Wash, from March 30, 2005, until April 6, 2005. This meeting represents an excellent opportunity to network with professionals in the field and to learn about the many different job options that are available to those studying andrology. This issue's article describes the less conventional career paths of two successful andrologists who each hold different industry positions. For those of you who are not yet fully committed to a future in academia or as a clinician, the following article may point you in a new and exciting direction. For those of you who already feel settled on your future plans, but remain curious and interested in new and unique opportunities, read on. To all of you, remember that if you like what you read here or would like to ask the authors questions, you can always speak with them and with all Society members at the annual meeting.

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