Drug Development: The Short Story
2. Discovery Reesearch
The "process" of drug development is generally divided into two stages: new lead discovery (preclinical research) and new product development (clinical development). The time-lines and expenses of these stages are radically different. This section will attempt to provide a broad overview of the activities required to successfully complete each phase of the development pathway.
In order to market a drug, pharmaceutical companies are required to prove three things:
- the drug is safe;
- it is effective in treating the specific disease for which it was designed; and
- the drug can be manufactured cleanly and reproducibly each time that it is prepared.
This process begins with Discovery Research. This department is tasked with finding new compounds and assuring that they are safe enough to test in humans. The tasks required to achieve this goal are numerous and require the expertise of a number of departments. These include:
- Research Planning - the management team which sets therapeutic targets, budgets, and resources.
- Chemistry - whose responsibilities are to prepare new chemical entities (NCEs) which can be screened for biological activity and to prepare compounds which have been found to be active (new leads) in quantities sufficient for advanced testing.
- Pharmacology/Molecular Biology/Screening - examines each NCE in a set of high throughput screens. This is referred to as primary screening which is used to determine if the compound is active (e.g. does it bind to the test enzyme more tightly than the control compound) or inactive. The majority of compounds tested do not show activity. However, when a molecule demonstrates high affinity for a target receptor, more rigorous testing (secondary screening) follows to assure that the initial results were correct.
- Safety Evaluation - demonstrates that the NCE and its metabolites do not accumulate and do not cause harm during short-term administration. These tests are generally carried out in bacteria and yeast (genetic effects) and at least two animal species.
- Formulations Research - develop a dosage form (pill, tablet, capsule, etc.) that is absorbed into the blood stream when administered and is stable when stored for long periods of time. The concentration in the blood is an important factor in early development. The potential new drug must reach and maintain a level sufficient to sustain its biological effect. These studies are initially conducted in animals, however, doses for human studies will be derived from these studies.
- Process Research - manufacture the NCE in quantity for advanced testing, dosage form development, and other support activities.
- Legal Affairs - writes and files the patents necessary to protect a company's inventions. Patents must be filed before any public disclosure of a new compound's structure or activity. If the compound is reported (disclosed) before the patent is filed, it is considered to be public property.
- Research Administration - collects the material generated by all of the departments and formats it into a request for exemption so that the NCE can be tested in humans. This submission is the Investigational New Drug application or IND.
Research is not an easy (or sure) process. During 1970, companies with membership in the Pharmaceuticals Manufacturing Association (recently renamed as the Pharmaceutical Research and Manufactures Association PhRMA) reported that they prepared 126,000 new chemical entities and screened 700,000. From this group, only 1,000 NCEs were promoted to be examined in the clinic.
The above is a very brief overview of preclinical research. This process begins with an analysis of the market potential for a given therapy and ends with three documents which detail the efforts of a number of professionals - a patent, a statement of clinical attractiveness, and an IND. These documents initiate the next phase in the drug development process - clinical trails.
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