Resources for IND Applications

Drug developers, or sponsors, must submit an Investigational New Drug (IND) application to FDA before beginning clinical research.

In the IND application, developers must include:

1. Animal study data and toxicity (side effects that cause great harm) data.
2. Manufacturing information.
3. Clinical protocols (study plans) for studies to be conducted Data from any prior human research.
4. Information about the investigator.

There are two IND categories:

1. Commercial
2. Research (non-commercial)

The IND application must contain information in three broad areas:

1. Animal Pharmacology and Toxicology Studies: Preclinical data permits an assessment as to whether the product is reasonably safe for initial testing in humans. Also included is any previous experience with the drug in humans (often foreign use).
2. Manufacturing Information: Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.
3. Clinical Protocols and Investigator Information: Detailed protocols for proposed clinical studies to assess whether the initial phase trials will expose subjects to unnecessary risks. Also, 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 a review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.

Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.

Each of the sections below contains information from CDER to assist in the IND application process.

 

Resources for IND Applications

The following resources include the legal requirements of an IND application, assistance from CDER to help you meet those requirements, and internal IND review principles, policies, and procedures.

1. Pre-IND Consultation Program

• CDER's Pre-Investigational New Drug Application (IND) Consultation Program fosters communications between sponsors and new drug review divisions to provide guidance on the data necessary to warrant IND submission.
• The review divisions are organized generally along therapeutic class and can each be contacted using the designated Pre-IND Consultation List (below image).

Guidance Documents for INDs

• Guidance documents represent the Agency’s current thinking on a particular subject. These documents provide FDA review staff and applicants/sponsors with guidelines for the processing, content, and evaluation/approval of applications and also for the design, production, manufacturing, and testing of regulated products.
• They also establish policies intended to achieve consistency in the Agency's regulatory approach and establish inspection and enforcement procedures.
• Because guidances are not regulations or laws, they are not enforceable, either through administrative actions or through the courts. An alternative approach may be used if it satisfies the requirements of the applicable statute, regulations, or both. For information on a specific guidance document, please contact the originating office.

• For the complete list of CDER guidance, please see the Guidance Index. Guidance documents to help prepare INDs include (See list below). 

1. 21CFR Part 312: Investigational New Drug Application
2. 21CFR Part 314: IND A_and NPA_Applications—for FDA Approval to Market a New Drug (New Drug Approval)
3. 21CFR Part 316: Orphan Drugs
4. 21CFR Part 58: Good Lab Practice for Nonclinical Laboratory [Animal] Studies
5. 21CFR Part 50: Protection of Human Subjects
6. 21CFR Part 56: Institutional Review Boards
7. 21CFR Part 201: Drug Labeling
8. 21CFR Part 54: Financial Disclosure by Clinical Investigators

ALSO READ: Role of the FDA in the Drug Development Process

Laws, Regulations, Policies, and Procedures

• The mission of the FDA is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook. The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S.
• The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.

Code of Federal Regulations (CFR)

• The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the Code Of Federal Regulations (CFR)
• The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. The FDA's portion of the CFR interprets the Federal Food, Drug, and Cosmetic Act and related statutes. Section 21 of the CFR contains most regulations pertaining to food and drugs. The regulations document all actions of all drug sponsors that are required under Federal law.
• The following regulations apply to the IND application process:

1. 21CFR Part 312: Investigational New Drug Application
2. 21CFR Part 314: IND A_and NPA_Applications—for FDA Approval to Market a New Drug (New Drug Approval)
3. 21CFR Part 316: Orphan Drugs
4. 21CFR Part 58: Good Lab Practice for Nonclinical Laboratory [Animal] Studies
5. 21CFR Part 50: Protection of Human Subjects
6. 21CFR Part 56: Institutional Review Boards
7. 21CFR Part 201: Drug Labeling
8. 21CFR Part 54: Financial Disclosure by Clinical Investigators

• Final Rule: Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans.
• Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs.

Manual of Policies and Procedures (MaPPs)

CDER’s Manual of Policies and Procedures (MaPPs) are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities. All MAPPs are available for the public to review for a better understanding of office policies, definitions, staff responsibilities, and procedures.

MaPPs of particular interest to IND sponsors include:

1. Emergency Use of an Investigational Drug or Biologic

• Emergency Use of an Investigational Drug or Biologic - Information Sheet
• Final Rules for Expanded Access to Investigational Drugs for Treatment Use and Charging for Investigational Drugs
• FDA proposes rules overhaul to expand the availability of experimental drugs. The Agency also clarifies permissible charges to patients.
• The Guidance for Institutional Review Boards and Clinical Investigators contains information on Obtaining an Emergency IND, Emergency Exemption from Prospective IRB, Approval Exception from Informed Consent, and Requirement Planned Emergency Research, Informed Consent Exception.
• Federal Register notice for Emergency Use of an Investigational New Drug; Technical Amendment
• Physician Request for a Single Patient IND for Compassionate or Emergency Use
• Instructions for Sponsors of Emergency Investigational New Drug (EIND) Applications for Antimicrobial Products. From the Office of Antimicrobial Products, Division of Antiviral Products

2. FDA IND Review Team

The review team consists of a group of specialists in different scientific fields. Each member has different responsibilities.

• Project Manager: Coordinates the team’s activities throughout the review process, and is the primary contact for the sponsor.
• Medical Officer: Reviews all clinical study information and data before, during, and after the trial is complete.
• Statistician: Interprets clinical trial designs and data, and works closely with the medical officer to evaluate protocols and safety and efficacy data.
• Pharmacologist: Reviews preclinical studies.
• Pharmakineticist: Focuses on the drug’s absorption, distribution, metabolism, and excretion processes.Interprets blood-level data at different time intervals from clinical trials, as a way to assess drug dosages and administration schedules.
• Chemist: Evaluate a drug’s chemical compounds. Analyzes how a drug was made and its stability, quality control, continuity, the presence of impurities, etc.
• Microbiologist: Reviews the data submitted, if the product is an antimicrobial product, to assess response across different classes of microbes.

ALSO READ: New Drug Application (NDA) Process