A look behind the scenes: Developing a new drug

Modern pharmaceutical production builds on our increasing knowledge of how molecules interact in the body. Some of the world’s most-talented scientists conduct extremely targeted research on the biochemical processes that play a role in diseases, and collaborate across a range of fields, such as biology, bioinformatics, pharmacology and medicine. Although biotechnology is playing an increasingly influential role in drug development, the majority of drugs still have a chemical pedigree.

Research: Finding a needle in a haystack

“Since many illnesses result from disrupted interactions of proteins in the body, we initially search for the target protein involved in the disease process,” as Dietrich, lab director in Development, explains the starting point for chemical pharmaceutical development. The search then begins for substances that influence the effect of the target protein in the desired way. There are so many potential candidates that they are often compared to the number of stars in the universe. Boehringer Ingelheim keeps 1.5 million of these in its substance library. Every day, robots systematically put 200,000 substances through high-throughput screening (HTS) to test their biological efficacy. When a test substance interacts with a target protein it’s designated as a “hit.” One high-throughput screening yields between 800 and 2,000 hits. Researchers then group the most promising substances with similar structures and evaluate them with regard to their biological effects and the manufacturing process. This ultimately yields between one and three substance groups.

The long road to perfection

These pharmaceutical leads, as they are called, are optimized in hundreds of individual steps, creating up to 10,000 substance variations. Unsuitable substances are rejected. The researchers document the physiochemical properties of the substances, including solubility, resistance to light, etc. keeping the substance’s eventual administration as a drug in mind. The few substances that make it through this selection process are not necessarily the most effective; rather, they meet all the key optimization parameters, such as side effects and tolerability. If the scientists believe the substance has a chance of becoming a successful drug, the company applies for a patent and moves the substance into preclinical trials. And while the active ingredient has made it through the first stage at this point, it is still less than halfway to the finish line.

Development: From active ingredient to drug

“We work in interdisciplinary scientific teams to study the effects and side effects of the substance in the preclinical trials. We compile our results in a pharmacological profile,” Dietrich explains about the next phase. Toxicologists create a toxicological risk profile for the substance at the same time. This data makes it possible to evaluate the potential risks associated with the active ingredient (such as potential side effects) and its manufacturing. The chemical drug research department works in parallel to develop a safe, robust and cost-effective synthesis process, to ensure that there is enough of the active ingredient available for clinical trials, while pharmaceutical drug development prepares the dosage form for the drug, whether tablet, lozenge, syrup, etc. This is also done ahead of time so that enough near market-ready clinical trial samples are available for the planned clinical trials. Accompanying analytical procedures document the properties of a drug and define quality objectives. 

Clinical trials: Proving the efficacy

Very, very few candidates make it all the way to clinical trials. From the 10,000 hit substances that were tested in the lab, only a couple dozen get to preclinical trials, and an average of just 10 make it to human clinical trials, with an average of only one receiving approval. The drug has to prove in three successive phases that it is harmless and effective in a large number of patients. If there is evidence that the drug isn’t adequately effective or the side effects are too severe, development on the drug is immediately halted.

Crossing the finish line: Approval

If the results of clinical trials are promising, Boehringer Ingelheim then applies to the relevant regulatory authorities for authorization to bring the drug to market. The application sometimes includes up to half a million pages of documentation. The authorization process can take from six months to three years before the drug can finally go into production. And then the next race begins: Improving quality of life.