Every day, scientists in the biopharmaceutical industry research the molecular underpinnings of disease, screen compounds against new disease targets, and conduct clinical trials with thousands of patients atlocations around the globe. The driving goal of the sector is to ﬁnd new medicines that improve medical care and address unmet medical needs.
In 2010, despite the challenging economic environment, the sector maintained its strong support for innovation. Biopharmaceutical companies invested an estimated $67.4 billion in the search for new medicines. Developing a new medicine is a long and complex process, with many setbacks and challenges. The R & D process is becoming increasingly difficult, expensive, time-consuming and risky, costing $1.3 billion on average.
Researchers are working to ﬁnd new ways to approach the R&D process to make it more efficient while maintaining the highest safety and efficacy standards. The process is evolving to make use of the latest statistical techniques and research tools.
Only about one in six drug candidates that enter clinical trials are ultimately submitted to and approved by the FDA, according to a study of the 50 largest companies – many candidates fail as late as phase 3 trials.For the small share of drug candidates that do become approved drugs, it takes about 10 to 15 years from the initial discovery to availability for treating patients. The process requires both flashes of inspiration and persistent dedication. Researchers must creatively tackle unforeseen challenges and thoroughly collect data on all aspects of the drug’s safety and efficacy.
Extensive basic research lays the groundwork for understanding the disease to be treated and, if possible, the underlying cause. Researchers may contribute to this work from across sectors, including academic institutions, government labs and biopharmaceutical companies.
With this knowledge, biopharmaceutical researchers look for a molecule or “lead compound” that may alter the disease course. They may screen compound libraries, develop a molecule from scratch or use some substance from nature as the starting point. After many safety and efficacy tests, they often redesign the most promising compounds to optimize their disease-ﬁghting properties. Often, hundreds of variations are pursued.
SOURCE: Pharmaceutical Research and Manufacturers of America, Drug Discovery and Development: Understanding the R&D Process, www.innovation.org.
The next step is to test the optimized compounds in the laboratory to find the most effectiveness lead with a safety profile that supports initial introduction into humans. Scientists try to determine how a compound works describes its safety profile
If the compound appears to be safe and effective, the company submits an Investigational New Drug Application to the FDA to seek approval to begin clinical trials.
A critical part of the R&D process is clinical research, the study of a pharmaceutical product in people. Clinical research involves both potential beneﬁts and potential risks to the participants, and research-based biopharmaceutical companies place great importance on respecting and protecting the safety of research participants, ensuring scientiﬁc integrity, and disclosing clinical trial results.
Before a trial begins, researchers develop a protocol, or plan, for the trial, laying out exactly what information they are collecting and how patients’ safety will be protected. The clinical trials process lasts an average of six to seven years and usually involves thousands of patients and several different phases of research:
Phase 1 trials (20 to 100 volunteers) – Phase 1 trials are usually performed in healty volunteers. These studies are designed to determine if a drug is safe in humans, what the safe dosing range is, and if the drug should move on further testing.
Phase 2 trials (100 to 500 patients) – In phase 2 trials, researchers study patients with the disease or condition in question, and also identify common, short-term side effects associated with the treatment.
Phase 3 trials (1,000 to 5,000 patients) – Phase 3 trials study a drug in a much larger patient population and allow researchers to collect data on a drug’s safety and efficacy for the evaluation of the overall beneﬁt-risk proﬁle of the treatment for a particular patient population. Phase 3 trials are the longest trials, and often take place in literally hundreds of sites across the United States and throughout the world.
If clinical trial ﬁndings indicate that a drug is both safe and effective, the company ﬁles a New Drug Application (NDA) or a Biologic License Application (BLA) with the FDA to request the medicine be reviewed for approval. The FDA reviews the application, which can run 100,000 pages or more, to assess the data from all testing done since the beginning of the process. The FDA uses these data to determine whether a drug’s or biologic’s beneﬁts outweigh any risks, what information should be included in the medicine’s labeling, and whether the proposed manufacturing process is appropriate.
Research does not end with FDA approval. Companies continue to monitor the safety of the product as long as it is available to patients, and often conduct research on new potential beneﬁts of the medicine in other disease areas or patient populations. For the entire life of the medicine, teams of scientists and physicians collect safety data on a daily basis and report potential problems to the FDA. For example, the FDA requires:
In addition, the FDA may require companies to conduct “Phase 4” studies as a condition of approval to evaluate the long-term safety and effectiveness of a medicine or its effects on a subset of patients.
Companies often also continue to research expanded uses and beneﬁts of a medicine after approval, leading to growing understanding of the full beneﬁts of a given treatment. For instance, the medicine may be used earlier in the disease process, for different diseases, in combination with another medicine, or in combination with speciﬁc biomarkers to better predict response to treatment. As research accumulates after approval, new beneﬁts of a medicine are identiﬁed.
Research and development of new medicines is not a static process. Researchers are always looking for new and better ways to innovate. As the process has become more complex, expensive, and time-consuming in recent years, researchers have redoubled their efforts to improve the R&D process. They are using new technologies and more sophisticated methods for analyzing data to make the process more efficient while still maintaining the highest safety standards.
SOURCE: Pharmaceutical Research and Manufacturers of America, Pharmaceutical Industry Profile 2011