Have you ever wondered about the long and arduous journey that a common drug like paracetamol goes through before coming to pharmacy stores? The efforts put into making this journey possible? The time and money spent on developing a single drug?
If yes, then I would like to take you through it. But if not, then maybe after reading this, you will appreciate the efforts put in by not only the scientific community but the pharma industry as well to find new medicaments.
Only a few of us know that the journey begins in a university laboratory where researchers, spending hours and hours to understand the processes behind a disease, stumble upon a potential target. This target can be a gene or a protein instrumental in the progression of the disease at a cellular or molecular level.
It is through blocking this target that the disease could be stopped or so it is presumed.
THE CHILDHOOD – SIMULATION OF A DRUG
The first step, structural predictions, is performed in silico with help of computer algorithms and simulators. The predicted molecules are somewhat modified from other drugs, cellular molecules or natural compounds. With current advancements in technology, thousands of molecules can be screened by high-throughput screening and the most suited results are the so-called “lead compounds”.
These substances have an expected biological or pharmacological activity, but they are far from being the final drug. They are more likely a prototype, which can be modified in order to be more functional or less toxic. During in silico analysis, more than 10,000 compounds are identified and their chemical, physical and biological properties are deeply examined.
Only about 20 compounds will be chosen as leading compounds and they can go toward the next step.
The ADOLESCENCE – LABORATORY TESTING
Now the actual laboratory tests begin. In this ‘preclinical trials’, substances are tested not only in vitro, on cell cultures or on artificial systems which mimic biological environments, but also in vivo, on model animals.
The first hints about toxicity, strength, and doses are registered. But they are better determined with in vivo tests on animals. These latter experiments elucidate the drug metabolism much better. At the end of the preclinical trial, only a few leading compounds have the right property to reach the last phase, the ‘clinical trials’.
THE ADULTHOOD – CLINICAL TRIALS
The last, but the most essential part of the drug testing is the most expensive and time-consuming. There are three mandatory phases before the final approval and a fourth one, which is when the drug is officially ratified.
Phase I clinical trial involves only a few tens of healthy volunteers and it mainly evaluates the drug tolerance.
The kinetics of the compounds and their possible side effects are monitored. During this step, many drugs are excluded from the study due to bad kinetics.
Thereafter, phase II trials include a bigger cohort: 100-300 people affected by the disease. After informed consent, patients are treated with different doses of the new drug or with a placebo (a compound that has no biological nor pharmaceutical activity in respect to the target under examination). Basically, a dummy.
Further, to avoid psychological influences, doctor implement a so-called “blind study”. The doctor knows which therapy is given to the patient, but the patients do not. Whereas, in a “double blind study”, neither the doctor nor the patient knows which treatment is administered. However, an external group of scientists monitors these type of studies.
THE OLD AGE – APPROVAL
This is not the end. A more robust phase III clinical trial remains. Groups of scientists and doctors monitor a broader number of patient (up to 3000) in this phase. These patients comprise of different hospitals and, for a better study, even from different nations.
The goal of the analysis is to confirm the efficacy and the safety, to monitor the long-term side effects and to improve the doses and the way of administration.
If all goes according to plan, the drug then goes for approval by the national medicine agency (for Europe it is the European Medicines Agency (EMA) and for the United states it is the Federal Drug Administration (FDA)). The authorities check the data thoroughly and decide if the new drug can be produced and sold.
However, the controls do not end here! The scientists can decide to start a phase IV clinical trial, which involves a bigger number of patients to assess further safety concerns, efficacy and long-term side effects.
Moreover, there is an external national committee, which registers every side effect and monitors constantly the efficacy of the medicine. The process, called as pharmacovigilance lasts as long as the drug is sold and used.
A lifetime, huh!
Each year, there are only a couple of dozen new drugs licensed for use. But in their wake, there are hundreds of thousands of candidate drugs that fail to clear these hurdles.
On an average, the research and development journey of these new drugs that make it to market takes around 12 years and cost more than € 1.5 bn.
Wow, that’s pretty huge.
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