Learn how the R&D process works

Our mission at ESTEVE is to develop innovative new medicines to treat diseases that today are not well controlled by existing therapies. The development of a new medicine is a highly complex process that takes up to 10 - 15 years to complete. Furthermore, the large majority of potential new medicines do not pass the rigorous testing that is required to ensure that they are safe and have the required level of effectiveness for patients.

For every 5,000 - 10,000 compound molecules that enter the drug discovery and development process only 1 is approved for use by patients. Consequently the successful development of a new medicine requires an outstanding team of researchers and clinicians with tremendous dedication and perseverance. The cost to bring a new drug to market has been estimated at approximately 1.800 Million of USD. This figure includes all development costs as well as the cost of drug development failures (Source: How to improve R&D productivity: the pharmaceutical industry’s grand challenge; Nature reviews 2010).

Esteve R&D. Research & Development process

6 Stages

The process to develop a medicine can be divided into 6 stages each of which needs to be successfully completed before a potential medicine can move into the next stage.

A new potential medicine can be discovered in a number of ways, but the Discovery Stage is typically composed of two main activities. The first involves the identification of a component of the human body (so-called “targets”), which, if manipulated or changed in some way, can have a positive effect on the course of a disease. The majority of such targets are proteins or enzymes that have discrete functions in the human body. The second step involves the identification of how to correctly manipulate the target. In many cases, new medicines are compounds that when they bind to the target, cause it to change its behaviour thus alleviating the disease, however in other cases the target itself may be the medicine, as is the case for Insulin in diabetics. Consequently, this phase is completed once a target has been identified and evidence has been collected that it is of relevance to a disease and once the approach to manipulating that target has been defined. If the approach identified is the development of a chemical compound that binds to or otherwise interacts with the target, the first such compounds will also be developed in this stage.

Preclinical development involves all of the testing necessary to provide as much evidence as possible that a new potential medicine will be safe when tested in humans. Additionally, this stage of development also looks to provide evidence that a new potential medicine will work. Preclinical testing today includes test tube experiments supported by computer simulations. However it is still a requirement that all potential new medicines undergo a series of tests in selected experimental animals to further confirm their safety prior to human testing. In this stage of development, the compounds initially developed in the Discovery stage are sequentially improved by chemists in order to develop a final candidate compound for clinical testing.

Phase 1 clinical trials are designed to prove that a new potential medicine is safe for use in humans. The trials initially study the effects of giving healthy volunteers a single dose of a compound, and if no adverse effects are seen, a second phase 1 study will be done to give increasing doses of the compound to healthy volunteers in order to establish safety at higher doses. In such studies the volunteers are carefully monitored to ensure that their safety is not compromised. A typical phase 1 clinical trial may include between 20 and 100 volunteers.

Once a compound has been proven safe in phase 1 clinical trials, the compound must be tested for signs of efficacy in patients that have the disease against which the medicine is being developed. In these trials patients may also be given different dose levels of the compound to understand which dose might be most appropriate to treat the condition. While the ability of the compound to improve the disease condition is the main element being evaluated in phase 2 clinical trials, the safety of the compound and the patient’s ability to tolerate taking it are also rigorously studied. A new potential medicine passes phase 2 clinical trials, if a dose of the compound can be identified which optimally balances having a positive effect on improving the disease while minimizing side effects and their severity. Phase 2 clinical trials typically involve between 50 and 250 patients.

In phase 3 clinical trials the objective is to prove with a high degree of certainty that a compound is effective and safe in patients. This degree of certainty is often referred to as statistical significance. In order to generate statistically significant results that prove that a potential new medicine is effective and safe, the compound must be tested in a much larger number of patients. Often in phase 3 trials, the potential new medicine being tested is compared to the medicine that today is most often used to treat the same disease (when a treatment is available). In this case, the objective is to demonstrate that the new compound is much better at treating the disease than the currently available medicine. In other situations it may be sufficient to compare the new potential medicine to placebo, that is comparing it to a pill that does not contain any of the new compound. In this case the objective is to demonstrate that the new medicine can significantly improve a disease when compared to not treating it (which is the case when no medicine is currently available). For a compound to successfully pass this stage, it typically needs to undergo 2 phase 3 clinical trials, sometimes more, and each trial will typically involve over 500 patients.

Once all of the results from stages 1 to 5 have been obtained and documented, they need to be reviewed and approved by the governmental regulatory agencies before a new medicine can be made available to patients. This step is critical as it ensures an objective review of data is performed such that only those compounds that are indeed effective and safe are made available. While this final stage of the process is decided by the regulatory agencies, the same agencies are also collaborators throughout the other stages of the process shown above. Thus the entire process is one in which the regulatory agencies provide advice and feedback which is intended to help optimize the process itself.

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