The number of possible molecular structures is greater than the number of seconds that have elapsed since the Big Bang. It is estimated at 10 to the power of 60.

Many of these molecular structures have never existed. Using their expert knowledge, as well as state-of-the-art scientific tools, Roche researchers produce thousands and thousands of new synthetic compounds in the laboratory, ‘inventing’ them by combining already known elements.

They then screen each one to find out which of them has what it takes to become a drug.

It will take about 12 years until your doctor can prescribe it.

New insights into the molecular cause of disease are the starting points for innovative research strategies leading to new, selectively acting drugs.

Once a target is identified, researchers develop study designs to show how drug candidates affect this specific biological structure or activity.

Substances with the desired effect are then evaluated in further laboratory tests or with computer programmes and then often modified.

We want to develop new treatments and test the efficacy of new compounds. We want to cure serious illnesses or at least relieve symptoms. We want to save lives.

To achieve these goals, even in the 21st century, medical research needs animal studies. After all, many investigations can only be performed in the living organism.

For example, it is often only animal studies that reveal the dangerous side effects of experimental drugs that would otherwise be hard to recognise. In other words, animal studies serve as a safety insurance for patients.

Medical research respects all living creatures – also those used in experiments

Roche deals responsibly with every living creature entrusted to it. Only promising drug candidates are tested in animals at all.

Unnecessary suffering and pain are avoided. All experiments are subject to authorisation. The highest ethical criteria apply to animal studies.

As well as national and international guidelines, Roche has imposed high voluntary standards on itself, its employees and contract research companies. Also wherever possible, animal studies are replaced by alternative methods, which Roche is constantly refining.

The real challenge for drug candidates begins once they pass the initial tests. They have to show in clinical trials that the potential medicine is effective and well tolerated.

Clinical testing proceeds in four phases. Only when a drug candidate has successfully passed one phase can it move on to the next.

Phase I: Tolerability and Safety

Drug candidates are first tested for safety and tolerability in studies with healthy volunteers. These studies are conducted in dedicated clinical facilities that ensure participants the best possible care.

Researchers can see how the new agent behaves in the human body and obtain preliminary information about its effects and the most appropriate dosage.

Phase II: Clinical Efficacy

The next step is to confirm the drug’s presumed mechanism of action, i.e. to prove it’s effective.

Researchers work with carefully defined groups of patients, giving them a range of dosages. This provides the information needed to identify the ideal treatment dose.

Patients enrolled in phase II studies are cared for by physician investigators and are observed closely in an effort to identify potential risks as early as possible.

Phase III: Documenting Treatment Outcomes

Only now does the developer test the drug in large-scale trials involving up to 5,000 patients, under conditions that closely resemble the clinical setting the drug is intended for.

This provides a realistic picture of how the drug will perform in clinical use. The information gained in this phase will also be important for marketing the drug when the time comes.

Phase IV: Ongoing Surveillance

Even after a drug is approved, it remains under expert surveillance. All side effects observed in patients taking a drug must be recorded and listed in the package leaflet.

Clinical trials produce vast amounts of raw data requiring careful handling and analysis. The results are then presented at medical meetings and published in medical journals.

Clinical trials follow a clear plan or ‘design’. Each sub study serves to answer a single important question. Careful data handling and analysis are a must.

To analyse trial data, researchers rely on tried and tested statistical methods, which have to be specified in a filing with the regulatory authorities before the trial even begins. This makes it possible to monitor and check what’s happening to the data at any time.

At participating trial centres, the bulk of the data is entered directly online and electronically processed for submission to the authorities.

Phase III clinical trials are conducted under the direction of an independent specialist in the disease area of interest. This ‘principal investigator’ is also the one who will present the results at a medical meeting or in a medical journal — even if the trial medication fails to produce the desired treatment response.

In addition, Roche publishes regular updates on its clinical trials at www.rochetrials.com.

Every country requires drugs to pass regulatory muster before letting them onto the market.

The regulators' task

Every country has a special regulatory agency to check and monitor the safety and efficacy of medicinal products. In Switzerland it’s Swissmedic; for the EU countries it’s the EMEA; and in the United States it’s the FDA, probably the best-known drug regulatory agency in the world. Most regulators also inspect the production plants for all drugs approved for marketing within their jurisdictions.

Regulatory review

When a new drug is submitted for approval, regulators require comprehensive documentation. This usually fills hundreds of files, many of which have to be submitted in multiple copies.

It can take months to years for the authorities to complete their review.

During this time the drug maker and the authorities will be in regular contact with each other. A positive decision from a regulator means that the drug can be marketed within its jurisdiction.

The package leaflet – a thumbnail description of a new drug

The package leaflet is a summary of all the data on a drug. It describes the use(s) for which the drug has been approved, the way(s) in which it should be taken, and the side effects that might occur.

The package leaflet offers a thumbnail sketch that is designed to be understood by the general public.

Small amounts of a drug are enough for research and development purposes. Large amounts are required for use in clinical practice.

Scaling up the production of a new drug is always a challenge, no matter how often you’ve done it. Nothing but the highest standards of quality and precision are good enough. Most of the specialists who handle scale-up projects at Roche can draw on decades of experience.

The manufacturer formulates the drug as a pill, capsule, ampoule or prefilled syringe and packages it. He then ships the product to pharmacies in a carton together with the package leaflet — all in compliance with national regulations.

The drug is available on the market.

It has taken over 12 years and many steps since the first discovery of the molecule by our researchers.

Your doctor can now prescribe it for you whenever you need it.