Before a new agent is studied in humans, it undergoes preclinical testing. During this phase, the primary aim of the sponsor is to use laboratory or computer-based modeling to determine the agent’s action, metabolism, and glaring toxicities. The sponsor will want to be sure the agent will not expose people to excessive risk when evaluated in small, early stage clinical studies. The agent is also evaluated for potential commercial applications. Usually, the testing is conducted using mice or rats, then possibly in larger animals.

Clinical trials involving pharmaceuticals are classified by the FDA into four phases, organized by the position in the approval process the study falls into. Before a study can begin, an investigational new drug (IND) application must be submitted to the FDA and approved. The IND effectively makes the proposed drug “legal” for the purposes of conducting research leading to FDA approval for marketing. The sponsor (applicant) for an IND may be a drug manufacturer and/or marketer, or the investigator conducting the proposed clinical investigation. The IND application will contain information about the animal pharmacology and toxicity studies, information pertaining to how the drug will be manufactured and detailed protocols for proposed early stage studies. The sponsor must wait 30 calendar days after submission of the IND before conducting any clinical trials. During this time, the FDA will review the application to be sure the research subjects will not be exposed to unreasonable risk and advise the sponsor if additional information or time is needed. Another type of IND is used for expanded access or “compassionate use.” The expanded access IND requests approval to use an investigational drug outside of clinical trials to treat patients with serious or life-threatening conditions for which no alternative treatment exists.

Once approved, human trials may begin. Phase I involves a small number of subjects (5–100) and is designed to evaluate the initial safety, side effects, and dosing range of the new drug. Pharmacology (pharmacokinetics) and metabolism of the drug are also evaluated during this phase. Phase II trials are conducted by providing the drug to a larger number or subjects to check its effectiveness and continued safety. Phase III trials encompass giving the drug to large numbers of subjects and have the purpose of collecting additional safety information, comparing it to other available treatments and confirm its effectiveness. Information collected during this phase is used to evaluate if the drug can be used safely and is the basis upon which the FDA will decide whether or not to approve the drug. Phase IV studies are conducted after approval and after the drug has been marketed. During this phase, researchers learn how the drug effects various populations and may reveal side effects associated with long-term use [7].

Device studies are handled somewhat differently. According to FDA regulation 21 CFR 807 Subpart E [8], a 510(k) or premarket notification (PMN) is required to be made to the FDA to demonstrate that the device is safe and effective. The 510(k) process also involves an evaluation of whether the device is substantially equivalent (SE) or non substantially equivalent (NSE) to another device already approved for marketing. Submissions are reviewed and processed by the Center for Devices and Radiological Health (CDRH) within the FDA. Within the CDRH, the Office of Device Evaluation (ODE) and the Office of In Vitro Diagnostics and Radiological Health (OIR) are responsible for clearance to market in the US. Reviewers consisting of field-specific engineers, physicians, chemists, and biologists among others determine if the device is SE or NSE. New devices must be classified according to FDA regulations into one of three classes known as Class I, II, and III, determined by the device’s intended use, instructions for use, and risk-based assessment. Class I and II devices are exempt in some cases from the PMN requirements and therefore do not require a 510(k) submission. All device classes are subject to a baseline set of requirements called General Controls as defined by the Food, Drug and Cosmetic Act (FD&C). Class I devices have a long and well-understood history of use and safety profile. Examples of Class I devices include manual surgical instruments, cotton gauze for external use, and wound hydrogels. Class II devices propose more risk than Class I devices and therefore are subject to additional controls such as guidance documents, special labeling, mandatory performance standards, and post-marketing surveillance in some cases. Examples of Class II devices include sutures, some lasers, intense pulsed light devices and some RF-generating devices. Class III devices are those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury. Class III devices are subject to the PMN process and involves demonstrating SE to another legally US marketed device. Examples of Class III devices include injectable dermal fillers, most lasers used in dermatology practice, and wound dressings that contain human cells [9]. Section 515 of the FD&C Act, Chapter V: Drugs and devices contains information on the PMA process for devices that require it [10].