The process of bringing a new drug to market is a complex and highly regulated one.
Before a drug can be commercialized in the United States, it must be the subject of an approved marketing application according to current federal law.
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However, if a sponsor wants to use a new drug under development for clinical research purposes, and ship this drug to clinical sites in multiple states, they must seek an exemption from this requirement.
This exemption is obtained through the submission of an Investigational New Drug (IND) application to the FDA.
The Purpose of an IND Application
During the early stages of preclinical development, the primary goal of the drug sponsor is to determine whether the product is reasonably safe for initial use in humans.
They also aim to establish whether the compound exhibits pharmacological activity that justifies further commercial development.
Once a product is identified as a viable candidate for further development, the sponsor focuses on collecting the necessary data and information to demonstrate that the product will not expose humans to unreasonable risks during limited, early-stage clinical studies.
FDA’s Role in the Development of a New Drug
The FDA’s involvement in the development of a new drug begins when the drug’s sponsor, typically the manufacturer or potential marketer, wishes to test its diagnostic or therapeutic potential in humans.
This occurs after the sponsor has conducted preliminary screening of the new molecule for pharmacological activity and acute toxicity potential in animals.
At this point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system.
Types of IND Applications
There are three types of IND applications :
This type of IND is submitted by a physician who both initiates and conducts an investigation.
The investigational drug is administered or dispensed under the immediate direction of the physician.
A research IND may be submitted by a physician to propose studying an unapproved drug or an approved product for a new indication or in a new patient population.
Emergency Use IND
This type of IND allows the FDA to authorize the use of an experimental drug in emergency situations where there is not enough time to submit a standard IND application.
It can also be used for patients who do not meet the criteria of an existing study protocol or when an approved study protocol does not exist.
This type of IND is submitted for experimental drugs that show promise in clinical testing for serious or immediately life-threatening conditions.
It allows for the use of the drug while the final clinical work is conducted and the FDA review takes place.
Categories of IND Applications
There are two categories of IND applications:
These applications are submitted by pharmaceutical companies seeking to bring a new drug to market for commercial purposes.
These applications are submitted by academic institutions, private organizations, or other entities involved in research for non-commercial purposes.
Information Required in an IND Application
An IND application must contain information in three broad areas :
Animal Pharmacology and Toxicology Studies
This section includes preclinical data to assess whether the product is reasonably safe for initial testing in humans.
It also includes any previous experience with the drug in humans, such as foreign use.
This section provides information about the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.
The FDA assesses this information to ensure that the company can consistently produce and supply batches of the drug.
Clinical Protocols and Investigator Information
This section includes detailed protocols for proposed clinical studies to assess the risks involved.
It also provides information on the qualifications of clinical investigators who oversee the administration of the experimental compound.
Additionally, it outlines commitments to obtain informed consent from research subjects, obtain review of the study by an institutional review board (IRB), and adhere to investigational new drug regulations.
FDA Review and Approval Process
Once the IND application is submitted, the sponsor must wait for 30 calendar days before initiating any clinical trials .
This waiting period allows the FDA to review the IND for safety and ensure that research subjects will not be subjected to unreasonable risk.
During this time, the FDA may request additional information or clarification from the sponsor.
Resources for IND Applications
The FDA provides various resources to assist sponsors in the IND application process.
These resources include:
Pre-IND Consultation Program
The Pre-Investigational New Drug Application (IND) Consultation Program is designed to foster early communication between sponsors and new drug review divisions.
This program provides guidance on the data necessary to warrant IND submission.
The review divisions are organized by therapeutic class.
Guidance Documents for INDs
Guidance documents represent the FDA’s current thinking on particular subjects.
They provide guidelines to FDA staff and applicants/sponsors regarding the processing, content, evaluation, and approval of applications.
These documents also establish policies to achieve consistency in the FDA’s regulatory approach.
To find guidance documents related to INDs, visit the FDA’s website and search for “investigational” in the guidance document section.
Laws, Regulations, Policies, and Procedures
The FDA enforces laws enacted by the U.S. Congress and regulations established by the agency to protect consumers’ health, safety, and well-being.
The Federal Food, Drug, and Cosmetic Act is the fundamental law governing food and drugs in the U.S.
It sets standards to ensure the purity and safety of food, drugs, devices, and cosmetics, as well as truthful labeling and packaging.
Code of Federal Regulations (CFR)
The Code of Federal Regulations (CFR) interprets the Federal Food, Drug, and Cosmetic Act and related statutes.
It contains regulations pertaining to food and drugs, including those that apply to the IND application process.
The CFR is divided into 50 titles representing broad areas subject to federal regulations.
Section 21 of the CFR is particularly relevant to drug regulations.
Manual of Policies and Procedures (MaPPs)
CDER’s Manual of Policies and Procedures (MaPPs) provides approved instructions for internal practices and procedures followed by CDER staff .
These guidelines help standardize the new drug review process and other activities.
IND sponsors can review specific MaPPs related to their applications by searching for “INDs” in the CDER Manual of Policies and Procedures section.
Emergency Use Requests
For investigational biological products regulated by the Center for Biologics Evaluation and Research (CBER), sponsors can call specific phone numbers for emergency use requests.
For all other investigational drugs, there is a separate phone number.
After working hours, sponsors can contact FDA’s Office of Emergency Operations.
The Investigational New Drug (IND) application is a crucial step in the development of a new drug.
It allows drug sponsors to seek an exemption from federal regulations to transport and distribute investigational drugs across state lines.
By submitting an IND application, sponsors provide the FDA with essential information about the drug’s safety, manufacturing, and proposed clinical studies.
The FDA reviews the application to ensure that research subjects are not exposed to unreasonable risks.
Through various resources and guidance, the FDA supports sponsors in navigating the IND application process and works to protect public health and safety.