Investigational New Drug (IND) Applications for HCT/Ps: How do I get there?
Our industry of regenerative medicine has experienced major growth in the last decade especially when it comes to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). These novel therapies provide a myriad of applications for use in the treatment of diseases and injuries, ranging from orthopedic and ophthalmic conditions, to burns and degenerative disorders. As innovative as they are, getting these products to market to help impact the quality of life for patients is complex and the potential risks associated with their use are rigorously surveilled and regulated by the Food and Drug Administration (FDA). Major efforts go into the regulatory framework for development, clinical investigation, and then commercialization.
One area of this framework is the Investigational New Drug (IND) application process, especially relevant for HCT/Ps that do not meet the criteria for regulatory exemption under Section 361 of the Public Health Service (PHS) Act. Today we’re going to dive into the basics of IND applications for HCT/Ps and explore the FDA’s regulatory approach for getting an IND approved. Let’s go!
What are the regulatory frameworks for an IND application?
HCT/Ps are tissue products derived from humans (through the tissue and/or blood donation process) that are intended for implantation, transplantation, infusion, or transfer into a human recipient. HCT/Ps are regulated under two primary regulatory frameworks:
Section 361 of the PHS Act (21 CFR Part 1271 Human Cells, Tissues, and Cellular and Tissue-Based Products) [1] : For HCT/Ps that meet the requirements of being minimally manipulated and intended for homologous use only. These products are controlled in a manner to prevent communicable disease transmission and are not subject to premarket approval, therefore, the commercialization process is a little faster.
Section 351 of the PHS Act and The Federal Food, Drug, and Cosmetic Act (FD&C): HCT/Ps that are more than minimally manipulated or used for non-homologous purposes, or those combined with other drugs or devices, are regulated as drugs, biologics, or medical devices. These products require premarket approval typically via an IND application followed by a Biologics License Application (BLA).
What’s an IND application?
An IND application is a request from a clinical study sponsor (such as a researcher or company) to obtain authorization from the FDA to administer an investigational drug or biological product to humans (a.k.a clinical study/clinical trial). Before starting such a study/trial, an IND application must be approved by the FDA. Clinical studies are conducted to collect safety and effectiveness information in support of marketing applications, such as a BLA, for biologic and drug products [2].
Clinical studies must follow the Good Clinical Practice and Clinical Trials (GCP) regulations [3], [4] . These regulations protect the rights, safety, and welfare of human subjects participating in human trials. This ensures the quality, validity, and integrity of the clinical trial data, as well as promotes the availability of new medical products to the public [2] compliant with FDA regulations.
Components of an IND Application
Preclinical Data: Evidence from laboratory and animal studies demonstrating the safety profile of the HCT/P and supporting its rationale for human investigation.
Chemistry, Manufacturing, and Controls (CMC): Detailed information on the source of the tissue or cells, methods of processing, characterization, testing, and measures taken to ensure product quality and consistency.
Clinical Protocols: Proposed plans for clinical investigations, including study design, subject selection, dosing, endpoints, and safety monitoring procedures.
Investigator Information: Qualifications and credentials of clinical investigators responsible for conducting the study.
Informed Consent and Institutional Review Board (IRB) Approvals: Documentation ensuring that the rights and welfare of participants will be protected.
What does the FDA look for?
Here are some items the FDA looks for to ensure that INDs are safe for use in humans and that the clinical studies are designed to yield data integrity [5] :
Product Characterization: Clear definition and documentation of the product (i.e., source materials, processing, and testing).
Safety Data: Comprehensive preclinical data demonstrating safety (especially for products with novel manipulations or indications).
Manufacturing Consistency: Well documented procedures ensuring batch to batch consistency and quality.
Traceability and Donor Screening: Donor eligibility determination, screening, and disease testing.
Risk Mitigation: Strategies to monitor, detect, and manage adverse events during clinical trials.
Ethical Considerations: Protection of human subjects, including informed consent and IRB oversight.
The IND Process
Several key steps include, but are not limited to:
Pre-IND Meeting: Sponsors should schedule a pre-IND meeting with the FDA to discuss the proposed clinical program, clarify regulatory requirements, and receive informal feedback.
IND Submission: The sponsor submits the IND application with all required documents.
FDA Review: The FDA reviews the submission within 30 days and may request additional data and/or clarification.
Clinical Hold or Proceed: The FDA will allow the study to proceed, or if the FDA has concerns, they may place the IND on clinical hold until issues are resolved.
What happens if approved by the FDA?
Once clinical trials have demonstrated safety and effectiveness, sponsors can pursue commercialization through the following [3] :
Biologics License Application (BLA): For HCT/Ps regulated as biologics, a BLA must be submitted and approved before marketing in the United States. The BLA includes extensive data from clinical trials, manufacturing information, and labeling.
Establishment Registration: Facilities processing or manufacturing HCT/Ps must register with the FDA and list their products.
Post-Market Surveillance: Ongoing monitoring of product safety and effectiveness for adverse event reporting and periodic inspections is mandatory.
Compliance with Current Good Manufacturing Practices (cGMP): Manufacturers must adhere to cGMP requirements.
Engaging with the FDA early in development can provide critical guidance as well as investing in a robust quality management system and resources to meet and maintain cGMP compliance. The path to commercialization requires a thoughtful and methodical approach focusing on patient safety, scientific integrity, and regulatory compliance. By understanding the FDA’s expectations and proactively engaging with them, sponsors can accelerate the development of safe and effective products that transform patient care.
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Reference
[1] https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271
[4] https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/good-clinical-practice