Rob Lindberg, Ph.D., R.A.C., is the Center's BATON director. He holds a Ph.D. in Physiology and Biophysics. His specialty is microvascular physiology, with emphasis in endothelial function in inflammation, thrombosis and cancer.
Full Biography.
Pharmaceutical Drugs
Pharmaceutical drugs are generally synthetic small molecule compounds where the chemical composition is well-defined and characterized. Such therapeutic compounds fall under the regulatory jurisdiction of CDER. In addition, CDER regulates many biological compounds such as therapeutic monoclonal antibodies and other proteins, as well as immunomodulators and growth factors (see Biological Drugs).
A typical regulatory path for pharmaceutical drugs begins with an initial meeting between the drug sponsor and FDA officials from the appropriate CDER branch division. This meeting introduces the regulatory officials to the technology and sets expectations for all parties with regards to the preliminary data that will be required in a subsequent Investigational New Drug (IND) application to support the initiation of clinical research. See http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm for a useful summary of the IND process, definitions, etc.
The IND typically requires exclusive chemical characterization of the drug; a summary of relevant research data to date by the investigator or others; in vitro (test tube/molecular/cellular) and in vivo (animal) data to suggest safety and efficacy in relevant systems designed to model human physiology and drug ADME (absorption, distribution, metabolism, excretion) systems; manufacturing methods; and the design of the first series of human studies.
The FDA has 30 days to review the IND for safety and (barring any FDA action to the contrary) the sponsor is allowed to initiate clinical studies. Most often, the initial study is a relatively small (10 – 50 subjects) single-dose study in healthy human volunteers (Phase 1 clinical trials) to assess safety and pharmacokinetics (PK) of the drug across a range of doses for a given route of administration. A typical Phase 1 program will also include a multidose study, and may also assess drug-specific areas of interest (e.g., effects of food on PK, cardiovascular effects).
If Phase 1 study results warrant further development, the sponsor then initiates the first of several Phase 2 studies in groups (30 – 200) of volunteers that represent the targeted patient population (i.e., patients with the disease of interest). These studies are intended to establish clinical proof-of-concept as to the desired therapeutic action (efficacy) as well as safety in the intended patient population.
Upon completion, two Phase 3 trials are conducted in larger patient populations (often in the thousands) to definitively demonstrate safety and efficacy endpoints. During the Phase 1 – 3 clinical development, a variety of additional animal safety studies must be conducted to support the typically longer duration Phase 2 and 3 studies as well as to address specific areas of safety (e.g., carcinogenicity, effects on the reproductive system, etc.).
If these studies are successful and there are no additional safety concerns, the sponsor submits the aggregate development data (animal, human, and manufacturing) as a New Drug Application (NDA) to the FDA for its review. Approval of the NDA constitutes approval by the FDA to register and market the drug in the U.S. Of course, the FDA reserves the right to require additional studies, audit manufacturing facilities, or stop a study at any step along the way. Even after approval, the FDA may require the sponsor to perform additional post-marketing studies (Phase 4).