Innovation process

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.

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.

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

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.

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

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.

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.

Only now does the developer test the drug in large-scale trials involving up to several thousands of 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.

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.

The results of the clinical trials 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.

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.

All of Roche’s trial protocols are posted along with the results of trials once they are completed on two websites that are available to the public: www.clinicaltrials.govand www.rochetrials.com. We are also committed to publishing all of our global studies in medical journals.

In Switzerland the regulatory agency is Swissmedic; for the EU countries it’s the EMA; 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.

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.

Scaling up the production of a new drug is always a challenge, no matter how often it is done. 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.

Your doctor can now prescribe it for you whenever you need it. For us it is a big satisfaction to be able to offer a new treatment option to a patient who needs it.

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.