What Is an Investigational New Drug Application (INDA)?
The investigational new drug (IND) application is a regulatory submission made by the drug sponsor to the FDA (Food and Drug Administration), seeking permission to conduct clinical trials and transport or distribute the investigational drug across state lines before it has received marketing approval. The primary purpose of the IND is to demonstrate the drug's safety and pharmacological activity in early-stage clinical studies while ensuring it does not pose unreasonable risks to human subjects. The FDA's involvement begins when the drug sponsor, after conducting preclinical studies, desires to test the drug in humans, and the molecule transitions to a new drug status, subject to regulatory oversight.
What Are the Types of IND?
There are three types of investigational new drug (IND) submissions:
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Investigator IND: This type of IND is proposed by a physician who takes the lead in initiating and conducting a research study. The physician directly supervises the administration or dispensation of the investigational drug. A physician may submit a research IND to propose the study of an unapproved drug or an approved product for a new indication or in a different patient population.
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Emergency Use IND: In situations where there is an emergency and there is not enough time to submit a standard IND application in accordance with the regulations stated in 21 CFR (code of federal regulations), the FDA can authorize the use of an experimental drug through an emergency use IND. This type of IND is also used when patients do not meet the criteria of an existing study protocol or if there is no approved study protocol available.
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Treatment IND: A treatment IND is submitted for experimental drugs that show promise in clinical testing for serious or immediately life-threatening conditions. It allows patients to access the experimental drug while the final clinical trials are being conducted and the FDA review is underway.
What Are the Categories of IND?
The two main categories of IND are as listed:
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Commercial IND: A commercial IND is submitted by a pharmaceutical company or drug manufacturer with the intention of developing and eventually marketing the investigational drug as a commercial product. The company is responsible for conducting extensive preclinical and clinical studies to establish the safety and effectiveness of the drug. The commercial IND application includes comprehensive data on the drug's formulation, manufacturing processes, preclinical studies, proposed clinical trial protocols, and plans for monitoring and ensuring patient safety throughout the study.
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Research IND: A research IND is usually submitted by a physician or investigator who intends to conduct a study to gather data on the safety, efficacy, or other aspects of an investigational drug. The purpose of a research IND is primarily to generate scientific knowledge rather than commercialize the drug. The research IND application includes information on the study objectives, design, and methodology, as well as details on the investigational drug and its proposed use.
What Are the Components of an IND Application?
The IND application comprises several essential components that provide crucial information about the investigational drug and its proposed use. These components include:
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Animal Pharmacology and Toxicology Studies: This section presents preclinical data obtained from studies conducted on animals. The purpose is to evaluate the drug's safety profile and assess whether it is reasonably safe to proceed with human testing. Additionally, any previous experience with the drug in humans, particularly its use in other countries, may be included in this section.
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Manufacturing Information: This component provides detailed information about the drug's manufacturing process. It includes data on the drug substance's composition, the manufacturer's identity, stability studies, and quality control measures employed during manufacturing. This information ensures that the company can consistently produce and supply batches of drugs that meet the necessary standards.
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Clinical Protocols and Investigator Information: In this section, the IND includes comprehensive protocols for proposed clinical studies. These protocols outline the objectives, design, and methodology of the clinical trials. They aim to assess the drug's safety and efficacy in human subjects. Additionally, information about the clinical investigators involved in overseeing the administration of the experimental compound is provided. This includes their qualifications, typically as physicians, to ensure they are capable of fulfilling their responsibilities in conducting clinical trials. The IND also includes commitments to obtain informed consent from research subjects, to undergo review by an institutional review board (IRB), and to adhere to the regulations governing investigational new drugs.
What Is the Process of IND Application?
The process of submitting an IND application involves several steps and interactions between the sponsor (pharmaceutical company or investigator) and regulatory authorities, such as the FDA in the United States. The process of IND application is as follows:
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Pre-IND Meeting: Before submitting the IND application, the sponsor may request a pre-IND meeting with the FDA. This meeting serves as an opportunity to discuss the proposed clinical trials, study design, endpoints, and any specific regulatory requirements. The FDA provides guidance and clarifies expectations during this meeting.
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Compilation of Data: The sponsor gathers comprehensive data on the investigational drug, including preclinical studies, manufacturing information, and proposed clinical protocols. This data is compiled to support the safety and efficacy of the drug and to demonstrate the ability to conduct clinical trials.
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IND Application Submission: The sponsor submits the IND application to the regulatory authority, such as the FDA. The application includes all the necessary information and documents required by the regulatory guidelines. This typically involves the completion of specific forms, providing a cover letter, and organizing the supporting data.
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IND Review and Safety Assessment: Upon receiving the IND application, the regulatory authority reviews the submission to ensure that all required information is included. The review process involves evaluating the data to assess the safety of the drug and to determine if the proposed clinical trials expose subjects to unreasonable risks. This review process helps safeguard the rights and welfare of research participants.
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Communication and Clarifications: During the review process, the regulatory authority may request additional information or clarification from the sponsor. This may involve addressing specific questions or concerns related to the investigational drug, study design, or patient safety.
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IND Clearance and Study Initiation: Once the IND application is reviewed and deemed acceptable, the regulatory authority provides clearance for the sponsor to proceed with clinical trials. The sponsor is typically required to wait for a specified period, often 30 calendar days, after IND clearance before initiating any clinical trials. This waiting period allows the regulatory authority to ensure that research subjects will not be subjected to unreasonable risks.
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Ongoing Reporting and Updates: Throughout the clinical trial process, the sponsor is responsible for ongoing reporting to the regulatory authority. This includes providing safety updates, study progress reports, and any significant changes to the investigational drug, study protocols, or adverse events.
Conclusion
IND application is a crucial step in the development and evaluation of new pharmaceutical products. It involves the submission of comprehensive data and information to regulatory authorities, such as the FDA, to obtain permission to conduct clinical trials. The IND application process ensures that investigational drugs are thoroughly evaluated for safety, efficacy, and manufacturing consistency before being tested in human subjects. Successful completion of the IND application sets the stage for further research and development, ultimately contributing to the advancement of medical science and the potential availability of new treatment options for patients.
