Drug Development Process

Pharmaceutical discovery—like all kinds of discovery—favors those who search in the right places. The drug-discovery process at Lilly begins by focusing on specific diseases and patient needs. Lilly discovery scientists search for biological targets within the body that play a role in a given disease. Targets can be part of the body (such as a protein, receptor, or gene) or foreign (such as a virus or bacteria). Lilly scientists identify, design, and synthesize promising molecules, screening perhaps tens of thou­sands, to assess their effect on the relevant biological targets. Molecules that have the desired effect on the target and meet other design criteria become “lead” molecules that go on to the next phase of development.

In this stage, Lilly scientists learn about how a compound is broken down and eliminated from the body and also how it might intervene in a disease. During this process, Lilly scientists use experiments in test tubes and animals as well as computer modeling and simulation to investigate questions such as: Is there a viable way to deliver the molecule to the biological target? How is this affected by chemical composition, the size of the molecule, and natural barriers within the body’s tissues and organs? Should the delivery vehicle be an oral method, an injection, or something else? How fast is the drug released and distributed in the body?

Researchers probe further to determine what dosage might be required for the medicine to be effective, and at what level it might be toxic to the patient. They also explore practical issues, such as whether Lilly will be able to manufacture the compound on a large scale, and whether the compound will be stable enough to remain effective and safe in the patient’s hands.

Preclinical Trials

Drug trials and approval processes aim to prove that a new drug candidate is safe for human patients and effective in treating the target disease. Before any human ever takes a new drug candidate, preclinical trials are conducted to obtain initial proof of safety and effectiveness. This may include data from tests done in laboratory dishes or other devices—called in vitro research—or from limited animal studies. These efforts can take several years to complete, and they demonstrate whether it is warranted to proceed to the next step.

Clinical Trials: Phase I

The next stage of the R&D process comprises three phases of clinical trials with humans. Lilly conducts clinical trials around the world and markets its medicines in 125 countries. That means we must complete regulatory approval processes in each country to bring innovative cures to patients worldwide. Phase I is intended to generate initial safety information about the drug in humans and assess how it behaves inside the human body.

Clinical Trials: Phase II

Phase II marks the beginning of controlled testing with patients who actually have the disease, to begin to demonstrate the medicine’s effectiveness. The total number of patients is still relatively small—perhaps several hundred people. This phase also produces additional information about short-term side effects and risks associated with the drug.

Clinical Trials: Phase III

Phase III seeks to provide definitive proof of the drug’s effectiveness and provides safety information from a much larger number of patients—from several hundred to several thousand—who suffer from the disease. The extensive data generated in Phase III provide a sound basis for extrapolating results to the general population and for developing the labeling information that is provided with the product.

In 2004, Lilly was one of the first pharmaceutical companies to launch a clinical-trial registry website to enable public access to results from our clinical trials. Today, this is required by law of all pharmaceutical companies. The results of applicable clinical trials of Lilly’s marketed products, per the FDA Amendments Act of 2007, can be found at the Government Clinical Trials website.

Regulatory Review

After extensive testing and study, a candidate drug is submitted for regulatory approval. The decision of the regulatory body determines whether or not the drug can be marketed to patients for approved uses. The review process can take anywhere from six months to two years or longer.

Post-Marketing Monitoring

Everyone is biochemically unique; therefore, individuals may respond quite differently to the same medication. Approved medications have been subjected to extensive testing for safety and efficacy. But even after medications are approved for general use, Lilly continues to collect product-safety information and monitor the safety profile of all Lilly products. In fact, the monitoring increases over time—through the collection of information from ongoing clinical studies, spontaneous adverse-event reports voluntarily reported directly from healthcare providers, and patients using the medicine.