Understanding Life Science Product Development: Target Identification and Validation

by Tony Pietsch

In the 1960s, Gordon Moore famously predicted that in the future, computer speed and capacity would double, and size and cost would shrink by half approximately every two years. Modern technology now exceeds Moore's Law, which is great for aficionados of MP3 players, PDAs and cell phones, but in the life sciences, we are constantly struggling with the disparity between the fast-paced world of IT and the extended timelines of medical device, diagnostics and especially drug development.

How do we ensure good information practices when technology is racing ahead of the products it is supposed to support? How do we ensure proper data collection and transmission when the formats and media we use may undergo several generational changes between the time a product is conceived and delivered to market?

Although IT is critical to the success of life science companies, its culture is often at odds with that of the industry it serves. In order to develop GIP, it is essential that we, as IT professionals, understand the world from the point of view of the pharmaceutical and medical device companies and fit what we do to the needs of an industry with dual challenges: an extremely long development cycle and products that are not launched at the same time or even with the same cycle time (and therefore offer no logical transition point for systemic technology upgrades).

How the Ball Starts Rolling: Launching the Product Development Process
Although pharmaceutical and medical device development may look like a linear process, it's important for IT professionals to recognize that these product cycles don't run in same linear time cycles as IT.

Before any drug, or biologic therapeutic development program, can begin, investigators need to identify a biologically relevant disease target, which they usually accomplish through basic research. For pharmaceutical companies, this target is typically an enzyme or DNA/RNA in a disease pathway that might be modulated by a new or existing drug. Drugs are often developed to improve upon existing "first in class" products. In medical device development, prototypes often build on improving existing technologies.

Basic research for biomedical discovery in the United States takes place primarily at universities and private research institutes, with funding from the NIH, at a public cost of approximately $38 billion (for the year 2004). Corporations spend a similar amount on early research for developing pharmaceutical drugs, vaccines or other biologics, medical diagnostics, devices and other life science health services.

Figure 1 illustrates the continuum of medical product development, from basic research through FDA approval. When basic scientific research bears fruit and generates ideas for new products, these ideas enter an increasingly rigorous evaluation process. Only a small percentage of candidates entering preclinical development survive to the market application stage.

Who's in Charge Here? Meet the Project Leader
In the pharmaceutical and biotech industry, a principal investigator working in a particular therapeutic area typically leads the target identification effort. In other life science industries, a program manager will usually lead a similar effort. For the IT community, it is important to understand that this leader will "own" responsibility for the discovery or invention of the drug or device all the way through the development process, beyond production and into patient follow-up and clinical results. In fact, this responsibility can even continue long after the drug or device has received FDA or other international regulatory approval, lasting more than 20 years —a period of time that exceeds the life cycle of nearly every IT project or architecture. This process represents the end-to-end relationship with IT in life science industries that drives the need for GIP.

Evaluating the Candidate Drug or Device
Once a target has been identified, one of the first tasks is to identify the contents of the "black box label"—the FDA-mandated indications, instructions, warnings, etc. that are part of the product packaging when the drug or device reaches the market. Although the initial target label may not (and often doesn't) ultimately match the results of clinical development, it is the guiding document and is of paramount consideration during all phases of development.

If, during product development, contraindications emerge that had previously not been identified, a drug will almost certainly fail as formulated (at least for the intended target). In these instances, a company must reverse course and redesign the product, use an alternate candidate to reduce or eliminate the risk, or abandon the project if there are no other alternatives.

In order to facilitate any reworking of the product, the PI or PM must be able to access the data accumulated throughout the entire process because, as the corporate memory for the product, he or she will be called upon to cite data that proves or disproves specific courses of action that were taken, or that should be taken next.

Figure 2 offers a simplified view of the activities that may take place at each phase of development. In practice, however, the process is rarely as linear as the critical path may mislead the IT community to believe. Development of a drug or device is likely to take many twists and turns as luck and fate influence the results of each stage. Eventually, however, progress must return to that critical path.

For GIP, it is important that we build in the flexibility to allow reversals in the project position on the critical path and document accurately and retrievably each decision by the lead and his/her team. When a reversal occurs, it is important that the entire process be traceable so that regulatory agencies can assess the data with the same integrity that the original investigators did.

At the same time, we must be aware of trends in the marketplace and prepare for new product types that may emerge. Currently, for example, there is much talk about personalized medicine and also of the promise of "diagnosticeuticals," drugs customized to a group or single individual's disease state. As these and other shifts in the industry take place, we are likely to find both the timeline for development and the underlying processes significantly altered and must adjust for those changes as well.

Speaking of Oversight. . .
The FDA, which is responsible for assuring medical product safety, regulates the development of drugs, biologic therapeutics, diagnostics and medical devices throughout their pre-clinical and clinical phase and monitors them for continued safety after they are in use. Figure 3 shows the numerous points where the FDA is typically involved in a drug development program.

In addition to the three clinical phases shown, developers often meet with the FDA before submitting an investigational new drug application (IND) to discuss early development plans. (An IND must be filed and cleared by the FDA before human testing can begin in the United States; a similar process takes place in many other countries.) During the clinical phase, they submit new testing protocols and results on an ongoing basis, and also often request meetings to get FDA agreement on the methods they are proposing for evaluating safety or efficacy, as well as manufacturing issues.

In the context of IT, each arrow represents a point in the development program where any and all of the preceding project data may be reviewed. Hence, our objective for GIP must be to maintain the end-to-end continuity of all information that ultimately leads to the disease target validation, and the efficacy and safety of the product in humans.

Where Does IT Fit In?
It has often been observed that conforming to the FDA approval process for a single drug or medical device literally generates a truckload of paperwork. Best practices will significantly reduce the time to market and discontinuity from phase to phase, and there is compelling evidence that documenting and implementing GIP can reduce the cost of communication with US and international agencies by as much as two thirds.

Given the complexity of the life science product development process and IT's value in reducing and consolidating data and paperwork (and saving money), we have an essential role to play in all phases of the broader life science industry—if only we can recognize and come to terms with the unique needs of those we serve.

Note: The preceding figures have been extracted with permission from the FDA white paper entitled "Challenge and Opportunity on the Critical Path to New Medical Products" found at www.fda.gov/oc/initiatives/criticalpath/whitepaper.html.