Glossary for the Antibiotic Pipeline
Clinical trial: A research study that uses human volunteers to help test treatments for diseases and conditions.
Development phase: There are multiple phases in the development of a drug that indicate how far testing has proceeded. Each phase has somewhat standard parameters and specific requirements that must be met before a drug can progress to the next stage. Additionally, the elements of one phase may overlap or repeat in a subsequent phase. The progression generally is as follows:
Preclinical or nonclinical testing: Laboratory and animal studies are used to determine whether a drug candidate is safe enough to test in people. Drug developers must file an Investigational New Drug application with the Food and Drug Administration outlining the results of preclinical studies before clinical trials can begin.
Phase 1: Initial testing is conducted in a small number of healthy volunteers (20 to 80) to determine if the drug is reasonably safe. During this phase, developers examine how the drug is absorbed and metabolized.
Phase 2: Testing evaluates the drug candidate's effectiveness and safety in a group of patients (generally 30 to 300) who have the condition the drug is meant to treat. Drug developers examine the side effects and potential risks of the drug and the initial indications of its effectiveness. Phase 2 studies provide information on the optimal dose for the drug and how it should be administered.
Phase 3: The drug is tested in a large group (often 1,000 or more people) to gather evidence about the safety, effectiveness, benefits, and risks of the drug. Test subjects have the condition the drug is meant to treat. Phase 3 studies provide key information used by FDA in deciding whether to approve a drug for use.
New Drug Application: A drug developer requests approval to market a drug to patients by submitting a New Drug Application to FDA. This application contains the results of all animal and human studies of the drug, as well as information on its manufacturing. The agency reviews the application and decides whether the drug can be approved or needs additional testing.
Phase 4 (post-marketing studies): FDA often requires sponsors to monitor the risks and benefits of a drug after it has been approved and made available to the public. In some cases, post-marketing studies focus on a subgroup of the general population that could not be adequately evaluated during clinical testing, such as pregnant women.
Drug class: Drugs that work in a similar way and share certain common properties, such as chemical structure. For example, cephalosporin drugs are grouped together because they have the same chemical structure and work by preventing bacteria from creating a cell wall.
Drug development: The process by which a drug candidate goes through clinical trials to show that it is safe and effective in humans. FDA must review the results of this testing as well as manufacturing information before it will approve a drug for use in patients. During the development process, a drug candidate is tested in successive trials and must meet specified requirements before progressing to the next stage.
Drug discovery: Early laboratory research to identify and test promising compounds that could later become drugs.
Gram-negative bacteria: Bacteria that appear pinkish or red when subjected to the laboratory staining method known as the Gram stain test. Gram-negative bacteria readily acquire resistance to multiple drugs and easily confer resistance to other bacteria. These bacteria are wrapped in a double-layered membrane that makes them particularly difficult to attack with antibiotics. Gram-negative bacteria cause a wide range of serious infections, and some have become increasingly resistant to available antibiotic treatments. Examples of Gram-negative bacteria with known drug resistance are Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia, and Neisseria gonorrhoeae.
Indication: A drug's indication is the disease or condition it was approved by FDA to treat. Antibiotics may be approved for a number of conditions, including urinary tract infections, bacterial pneumonia, and skin infections caused by multidrug-resistant bacteria. Indications are described on the drug's label.
Qualified Infectious Disease Product (QIDP): Under the Generating Antibiotic Incentives Now (GAIN) Act signed into law in 2012, drug developers may request that FDA grant a QIDP designation to “an antibacterial or antifungal drug for human use intended to treat serious or life-threatening infections.” Antibiotics designated as QIDPs are eligible for incentives, including faster FDA review and, if they are approved for patients, an additional period during which they are free from generic competition.
PhRMA, “Drug Discovery and Development: Understanding the R&D Process,” http://www.innovation.org/drug discovery/objects/pdf/RD_Brochure.pdf.
National Institutes of Health, “NIH Clinical Research Trials and You,” http://www.nih.gov/health/clinicaltrials/basics.htm.
National institutes of Health, “Gram-negative Bacteria,” http://www.niaid.nih.gov/topics/antimicrobial Resistance/Examples/gramNegative/Pages/default.aspx
U.S. Food and Drug Administration, “FDA Drug Approval Process Infographic,” http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm295473.htm.
U.S. Food and Drug Administration, “The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective,” http://www.fda.gov/drugs/resourcesforyou/ consumers/ucm143534.htm.