Investigational New Drug Application Process: A Guide

The journey of a new drug from scientific discovery to a shelf stocked in a pharmacy is long and intricate. The investigational new drug application (abbreviated as IND) is a critical checkpoint within this process, ensuring the safety and ethical testing of potential medications before they can be widely used. With the global market for prescription drugs anticipated to reach a market volume of US$1.33 trillion by 2029, successful IND applications pave the way for the development of potentially life-saving healthcare solutions, ultimately improving patient outcomes and driving economic growth.

Today’s post explores the complexities of the investigational new drug application process, empowering healthcare professionals and researchers to navigate this critical stage of drug development.

The Importance Of The Investigational New Drug (IND) Application

The Federal Food, Drug, & Cosmetic Act empowers the Food and Drug Administration (FDA) to safeguard public health by overseeing the development and marketing of drugs. The IND application is a fundamental aspect of this regulatory framework. It permits researchers or sponsors to request authorization from the FDA to issue an investigational drug (a drug not yet approved for general use) to humans for the first time. By meticulously reviewing the investigational new drug application, the FDA ensures the following:

• The investigational drug’s safety profile is adequately understood through preclinical testing.

• The proposed clinical trial is well-designed, ethically sound, and lowers risks to participants.

• Qualified investigators with the necessary expertise will watch over the clinical trial.
• A successful IND application paves the way for developing potentially life-saving healthcare solutions, ultimately boosting patient outcomes.

The IND Application Process – A Step-by-Step Guide

The IND application process can be intricate, but understanding each stage allows researchers and sponsors to navigate it effectively. Here’s a breakdown of the essential steps:

Pre-IND Considerations

Before formally submitting an investigational new drug application, researchers or sponsors should conduct extensive preclinical testing, which includes laboratory and animal studies, to confirm a basic understanding of the investigational drug’s safety and potential therapeutic effects. Consulting with the FDA (pre-IND meeting), at this stage, is optional but can offer valuable insights and accelerate the IND review process.

Preparing The IND Application

The IND application is a comprehensive document highlighting the proposed clinical trial and all aspects of the investigational drug. The critical components of this process include:

• Cover Sheet (Form FDA 1571): This form provides basic information about the application, including the sponsor, investigational drug, and proposed clinical trial.
• Investigator Brochure (IB): This document summarizes all crucial information about the investigational drug, including its chemistry, pharmacology, toxicology, and potential risks and benefits for human subjects.
• Chemistry, Manufacturing, And Controls (CMC) Information: This section details the manufacturing process, quality control measures, and stability of the investigational drug.
• Nonclinical Pharmacology And Toxicology Information: This segment presents data from preclinical studies to establish a preliminary safety profile of the investigational drug.
• Clinical Protocol: This document meticulously details the design and methodology of the planned clinical trial, which includes the selection criteria for participants, dosage regimen, and data collection procedures.
• Investigator Qualifications And Agreements: This section contains information on the qualifications and experience of the investigators who will oversee the clinical trial. Agreements outlining their responsibilities and adherence to the protocol are also included.
• Labeling And Advertising Information: This section details how the investigational drug will be labeled during the clinical trial and outlines any planned advertising of the drug.
• Investigational Plan: This document describes the entire strategy for the development of the investigational drug, including timelines for future studies and potential marketing plans.

Assembling a competent team is vital when preparing an IND application. The sponsor (typically a pharmaceutical company, research institution, or individual researcher) takes the lead but may enlist regulatory consultants to ensure compliance with FDA guidelines.

Submitting The IND Application To The FDA

The FDA currently encourages electronic submission of IND applications to enhance efficiency. Associated fees must be paid when applying.

The FDA Review Process

Once submitted, the FDA meticulously examines the investigational new drug application. The review process typically involves several phases:

• Initial Review (30 days): The FDA conducts an introductory review to ensure the application is complete and addresses all necessary elements. Incomplete applications may be rejected and might require resubmission.
• Investigational New Drug (IND) Safety Review (30 to 90 days): This is a thorough review by FDA scientists and physicians to assess the safety of the proposed clinical trial and possible risks to participants.
• Clinical Hold (potential delays): If the FDA recognizes significant safety concerns, they may place a clinical hold on the trial, prohibiting its initiation until the concerns are addressed.
• Additional Information Requests (potential delays): The FDA may request additional information from the sponsor to clarify specific aspects of the application. This can extend the review timeline.

Open communication with the FDA throughout the review process is critical to address any queries or concerns.

IND Approval And Post-Approval Activities

Typically, upon successful review, the FDA issues an IND approval letter authorizing the initiation of the proposed clinical trial. However, it is possible that you may not receive an approval notification. The FDA will outline the reasons for rejection, allowing the sponsor to address them and resubmit the application.

Even after approval, the sponsor has ongoing obligations such as the following:

• Renewals: Typically, INDs remain valid for three years. Sponsors must submit a renewal application before the expiration date to continue the clinical trial.

• Reporting Adverse Events: Any serious adverse events experienced by participants during the clinical trial must be actively reported to the FDA.

• Amendments: If the sponsor plans to make significant changes to the clinical trial protocol or the investigational drug itself, they must submit an amendment to the investigational new drug application for FDA review and approval.

Key Considerations And Challenges

Despite its importance, the IND application process is not without its challenges. We are outlining a few common mistakes that might occur during preparation, including:

• Incomplete applications lacking crucial information.
• Deficiencies in the clinical protocol design raise concerns about participant safety or the study’s ability to yield meaningful results.
• Inadequate preclinical data to support the proposed clinical trial.

Strategies for a successful investigational new drug application submission involve:

• The time and cost associated with IND development and review can be significant. However, a well-prepared and comprehensive application streamlines the process and expedites the journey of a potential breakthrough drug toward reaching patients.

• Meticulously planning the clinical trial and ensuring the protocol adheres to ethical guidelines and best practices.

• Gathering comprehensive preclinical data to establish a strong safety profile for the investigational drug.

• Assembling a team of experienced professionals, including researchers, regulatory consultants, and statisticians, to prepare a high-quality application.

• Maintaining open communication with the FDA throughout the process to address any concerns promptly.

Final Thoughts

The IND application is a critical gatekeeper in the drug development process, ensuring new medication safety and ethical testing. Understanding its intricacies empowers healthcare professionals and researchers to navigate this crucial stage. By meticulously preparing the application and adhering to FDA regulations, sponsors can pave the way for developing potentially life-saving healthcare solutions and ultimately improve patient care.