RESEARCH AND DEVELOPMENT.
Innovation is in the DNA of our business. It's how we improve the lives of patients, change the way we manage healthcare and benefit society as a whole. But our innovation gene is just the beginning. Expressing it - discovering and developing treatments that relieve suffering, prolong life and improve quality of life - takes time, skilled people, significant resources, collaboration across sectors and boundaries and often endless experimentation to find new breakthroughs.
Developing new drugs is a long, complex and risky process with no guarantee of success. It all starts with an idea. From 10,000 screened molecules to 10 that will be patented and 1 that will pass all the stages of testing and clinical trials to become a drug, the path from innovation to patient is long (12 years on average), complex and expensive. There are a number of phases in this journey.
Discovery and preclinical research
At the earliest stage, the aim is to understand a disease and how to influence it, to identify a molecule or compound to be developed, to see if it has the potential to become a drug that can change the lives of patients.
The drug candidate first goes through a series of so-called "pre-clinical" tests. These tests are a necessary step before any testing on humans.
- Experimental pharmacology: efficacy tests are carried out on inert molecular systems, on cells and cultures and, finally, on animal models. This is the first proof of concept.
- Toxicology: these studies evaluate the risks of side effects of future drugs.
- Pharmacokinetics and drug metabolism: these studies focus on the pharmaceutical properties of the molecule such as absorption, metabolism, distribution and elimination. But they also aim to prove the pharmacological properties.
If the results of these studies are positive, the drug enters the human clinical trial phase.
2. Clinical development
In order to resolve further uncertainties about the benefits and risks of a new treatment, it must be tested in a clinical trial. Before embarking on the clinical trial process, which is usually a three-step process, a company or academic institution must submit a protocol for regulatory review, which details how the trial will proceed. The protocol is evaluated by an ethics committee, which consists of independent experts and representatives of the lay public.
Only one in ten drugs reaches the clinical trial stage. This starts with a small trial on healthy volunteers (phase 1) before moving on to larger and larger trials in phase 2 and 3. These are often multi-center trials, sometimes involving thousands of patients, conducted in several countries and regions, to determine whether the new drug is safe and effective. All trials must be registered in the publicly available database before the trial begins.
These three phases are carried out in hospitals or doctors' offices, under the responsibility of expert doctors: the investigators.
PHASE 1: TOLERANCE OR SAFETY
Increasing quantities of the new molecule are administered to healthy volunteers under close supervision. This phase makes it possible to evaluate the broad outlines of the product's tolerance profile and its pharmacological activity.
PHASE 2: PRODUCT EFFICACY IN SMALL POPULATIONS AND DOSE FINDING
This phase takes place in a small number of hospitalized patients. The aim here is to define the optimal dose, i.e. the dose for which the therapeutic effect is the best with the least side effects. Proof-of-concept studies are used to validate a new treatment hypothesis in patients.
PHASE 3: "PIVOTAL" STUDIES
In conditions as close as possible to the usual conditions of use of the treatments, the efficacy and safety are studied in comparison with the reference treatment or a placebo. This is verified on a large group of patients. Precautions for use and risks of interaction with other products are identified. The trials may cover several hundred to several thousand patients.
All clinical trials conducted in the European Economic Area must be carried out in strict compliance with Good Clinical Practice (GCP) guidelines, an international ethical and scientific quality standard for the design, registration and reporting of trials involving human subjects. Adherence to GCP means that subjects' rights are respected and that clinical trial data are reliable. Similarly, compliance with Good Manufacturing Practice (GMP) guidelines must be ensured so that products are manufactured consistently and controlled to quality standards.
During a trial, patients are randomly separated into two common groups. This randomization ensures that all recorded outcomes are due to the treatments provided and not to the method of patient selection. One group receives the study drug or treatment procedure, while the other group - the control group - does not. The control group may be offered an alternative to the study drug - including the best available therapy or, if not available, a placebo. Trials must include a wide variety of patients for whom the treatment is intended, including ethnic groups, children and the elderly.
In most trials, patients do not know whether they are receiving the treatment under study or a placebo/other known therapy. This process is known as blinding. Healthcare professionals involved in the trial may also be prohibited from knowing which patient is in which group; this process, in addition to the first, is known as "double-blinding." This protects the trial from bias.
Once the trial is complete, a team of independent, unbiased researchers analyze the results. A summary of the trial, whether positive or negative, must be disclosed in a publicly accessible database.
Only "original" drugs from the innovative pharmaceutical industry go through these long stages.
The "generic" version of a drug is a copy of the original molecule. It does not go through this long cycle of testing.
3. Regulatory approval
The information and results of all preclinical and clinical studies, as well as a description of the drug's manufacturing process, are compiled and submitted to regulatory agencies to demonstrate the safety and efficacy of the new drug. This constitutes a marketing authorization application (MAA), allowing the drug to be marketed and patients to have access to it.
Once a drug has been granted marketing authorization, it undergoes strict monitoring to detect any potential safety or quality problems. This process is known as pharmacovigilance and must be undertaken in accordance with Good Pharmacovigilance Practices (GPP), a set of measures defined by the EU. It is the responsibility of the company that has been granted marketing authorization to continuously collect and collate data relating to the safety, quality and efficacy of the medicine. All of this data is then accessible by the regulatory authorities.
Drug safety is a permanent concern for drug companies. Once a drug is dispensed to patients, pharmacovigilance accompanies it throughout its life and will also be the subject of rigorous procedures.
Any health accident related to the use of medicines is reported to the regulatory authorities within a mandatory timeframe.
Companies also submit a drug monitoring report every six months for the first two years of the drug's life, then every year for the next three years, and finally every five years for as long as the drug is on the market.
5. Drug Utilization Data
Data collected from patients and their use of medicines helps us to better understand diseases and patients and to inform the discovery and development of new or improved treatments.
A MAJOR RESEARCH EFFORT, SELF-FINANCED BY COMPANIES
The development of thousands of new drugs over the last 50 years has been financed by the innovative pharmaceutical industry and their ability to increase their R&D expenditure. Therapeutic innovation presents both a high cost and a major financial risk: the time required for research mobilizes large amounts of capital over a long period of time, for an uncertain result. Few drugs generate sufficient profits to cover all the research and development costs incurred.
In addition, companies can only rely on a limited number of drugs to finance their future R&D. Diversification of the companies' product portfolio allows them to minimize the risk associated with each drug. This phenomenon explains the recent mergers, which allow companies to achieve economies of scale.
Today, patent protection of molecules is one of the guarantees of financing future research, and therefore the development of new, vital medicines, with the best cost/effectiveness ratio.
R&D EXPENDITURE REPRESENTS AN AVERAGE OF 9.8% OF DRUG COMPANY SALES
The pharmaceutical industry is one of the economic sectors with the largest research effort.
Although the total research budget is lower in absolute terms than that of the automotive and aerospace industries, it represented 10% of the innovative pharmaceutical industry's turnover in 2017, compared with only 4.8% for the automotive industry.