Investigational New Drug
Encyclopedia
The United States Food and Drug Administration
's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. The FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk. If the application is cleared, the candidate drug usually enters a Phase 1 clinical trial
.
An IND must also include an Investigator's Brochure
which is a document intended to educate the trial investigators of the significant facts about the trial drug they need to know to conduct their clinical trial with the least hazard to the subjects or patients who will be enrolled.
, an independent body constituted of medical, scientific, and nonscientific members, whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial. The IRB must review, approve, and provide continuing review of the trials, protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
) in 1991, facing an influx of AIDS
patients seeking access to the drug. Seven patients continue to receive cannabis
from the government under the program.
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. The FDA reviews the IND application for safety to assure that research subjects will not be subjected to unreasonable risk. If the application is cleared, the candidate drug usually enters a Phase 1 clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
.
Criteria for application
An IND is required for a clinical study if it is intended to support a:- New indication
- Change in the approved route of administrationRoute of administrationA route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
or dosageEffective doseEffective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
level - Change in the approved patient populationPopulationA population is all the organisms that both belong to the same group or species and live in the same geographical area. The area that is used to define a sexual population is such that inter-breeding is possible between any pair within the area and more probable than cross-breeding with individuals...
(e.g. pediatric) or a population at greater or increase of risk (elderly, HIV positive, immunocompromised) - Significant change in the promotion of an approved drug
Application contents
The IND application must contain information in three broad areas:- Animal Pharmacology and Toxicology Studies - Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Also included are any previous experience with the drug in humans (often foreign use).
- Chemistry and Manufacturing Information - Information pertaining to the chemical composition, manufacturing methods, stability, and controls used for manufacturing the drug substance and the drug product. The chemical stabilityChemical stabilityChemical stability when used in the technical sense in chemistry, means thermodynamic stability of a chemical system.Thermodynamic stability occurs when a system is in its lowest energy state, or chemical equilibrium with its environment. This may be a dynamic equilibrium, where individual atoms...
and activity of the product must also have been tested. This information is assessed to ensure that the company can adequately produce and supply consistent and active batches of the drug. - Clinical ProtocolsClinical trial protocolA clinical trial protocol is a document that describes the objective, design, methodology, statistical considerations, and organization of a clinical trial...
and Investigator Information - Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Information on the qualifications of clinical investigators—professionals (generally physicians) who oversee the administration of the experimental compound—to assess whether they are qualified to fulfill their clinical trial duties. Finally, commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.
An IND must also include an Investigator's Brochure
Investigator's brochure
In drug development, the Investigator's Brochure is a comprehensive document summarizing the body of information about an investigational product obtained during a drug trial. The IB is a document of critical importance throughout the drug development process and is updated with new information...
which is a document intended to educate the trial investigators of the significant facts about the trial drug they need to know to conduct their clinical trial with the least hazard to the subjects or patients who will be enrolled.
Application categories
There are two main categories of IND: Investigator-initiated, and Sponsor-initiated. Investigator-initiated INDs are used when a physician wishes to perform a clinical trial to study an unapproved drug treatment, for example a new indication for an existing drug. Sponsor-initiated INDs are filed by pharmaceutical companies studying new drugs or new uses for existing drugs. Both of these types of studies require approval by an institutional review board (IRB)Institutional review board
An institutional review board , also known as an independent ethics committee or ethical review board , is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the...
, an independent body constituted of medical, scientific, and nonscientific members, whose responsibility it is to ensure the protection of the rights, safety, and well-being of human subjects involved in a trial. The IRB must review, approve, and provide continuing review of the trials, protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects.
Application submission
Most INDs are paper submissions. While only 12% of INDs are submitted electronically, 28% of IND amendments are submitted electronically as result of maintaining a growing number of INDs submitted electronically to date. Though the percentage of INDs submitted in eCTD format remained stable from 2008 to 2009, the number of IND amendments in eCTD format nearly doubled, indicating that companies are beginning to understand the benefits of electronic submissions.Additional regulations
- Experimental drugs under an IND must be labeled, "Caution: New Drug--Limited by Federal (or United States) law to investigational use.
Noteworthy examples
The FDA closed its medical marijuana IND program (the Compassionate Investigational New Drug programCompassionate Investigational New Drug program
The Compassionate Investigational New Drug program, or Compassionate IND, is a United States Federal Government-ran Investigational New Drug program that allows a limited number of patients to use medical marijuana grown at the University of Mississippi. It is administered by the National...
) in 1991, facing an influx of AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients seeking access to the drug. Seven patients continue to receive cannabis
Cannabis
Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...
from the government under the program.
See also
- Drug DevelopmentDrug developmentDrug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
- Drug DiscoveryDrug discoveryIn the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
- Expanded accessExpanded accessExpanded access refers to the use of an investigational drug outside of a clinical trial by patients with serious or life-threatening conditions who do not meet the enrollment criteria for the clinical trial in progress...
("compassionate use") - FDA Fast Track Development ProgramFDA Fast Track Development ProgramThe FDA Fast Track Development Program is a designation of the United States Food and Drug Administration that accelerates the approval of investigational new drugs undergoing clinical trials with the goal review time of 60 days...
- Inverse benefit lawInverse benefit lawThe Inverse Benefit Law states that the ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively a drug is marketed...
- New drug applicationNew drug applicationThe New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...