SBIA: FDA recently released an update to clarify when ‘Research’ vs. ‘Commercial’ should be selected on FDA Form 1571, and thus when electronic common technical document  or “eCTD” requirements would apply for an investigational new drug or “IND” application.

An IND is generally considered commercial when the product under investigation is intended to be commercialized at a later date. In this case, the sponsor should select “Commercial IND” on FDA Form 1571 Field 6B.

In comparison, an IND is generally considered research if the product under investigation is not intended to be commercialized at a later date.  In this case, the sponsor would select “Research IND” on FDA Form 1571 Field 6B.

Today, we are joined by Paul Phillips from CDER’s Office of New Drugs to talk about some similarities and differences in submission requirements for these two types of INDs.

Paul: Thank you Steve.  In terms of similarities, Commercial and research INDs are both expected to contain all:

1. A Cover Letter
2. The applicable FDA Forms, such as the 1571, 1572, and 3674, or for single patient expanded access INDs the Form 3926.
3. A Table of Contents
4. An Introductory Statement and General Investigational Plan
5. An Investigator Brochure
6. Clinical Components, such as the Protocol and a Summary of Previous Human Experience with the Investigational Drug
7. Nonclinical Components, meaning the Animal Pharmacology and Toxicology information,
8. Chemistry, Manufacturing and Controls (or CMC) information, and finally
9. Other information as necessary

I will point out that we often observe with research INDs that sponsor-investigators will address the requirements for nonclinical and CMC information by providing a Letter of Authorization, also known as an “LOA” from the commercial manufacturer of the investigational product.  The LOA allows FDA to reference the nonclinical and CMC information in the commercial manufacturer’s IND on behalf of the sponsor-investigator.  

In terms of differences, the key difference between the submission of commercial vs. research INDs is that commercial INDs must be submitted in eCTD format.  In contrast, research INDs are not required to use the eCTD submission format.  

The update to the FDA Form 1571 clarified that when a sponsor of a research IND submits either a Phase 2 or Phase 3 protocol, the IND will then be considered “commercial” and eCTD submission requirements would apply. In this case, the sponsor should normally select “Commercial” on the FDA Form 1571 Field 6B under “IND Type”.  However, if the product under investigation is still not intended to be commercialized at a later date, meaning the intent of the Phase 2 or Phase 3 protocol is solely for research, the sponsor should submit a justification explaining their rationale in the cover letter, along with the protocol, and the sponsor would select “Research” on the 1571. The FDA will review the sponsor’s rationale and if the FDA agrees, the IND will remain a “Research” IND and the eCTD submission requirements will not apply.  

I’ll finish by noting that in all cases, expanded access INDs and protocols should be marked as “Research” on the Form 1571 and are exempt from eCTD submission requirements.

SBIA:  Thank you, Paul.  We remind sponsors that research INDs in paper or non-eCTD electronic format should be mailed to the CDER Central Document Room located at 5901-B Ammendale Road, in Beltsville, Maryland. Sponsors submitting paper are expected to send their applications in triplicate, with one original and two copies.

For both research and commercial INDs, FDA will notify the sponsor of the date it receives the application.  An investigator may not administer an investigational new drug to humans until the IND application goes into effect.  The IND application goes into effect 30 days after FDA receives the application, unless, 1. The FDA notifies the sponsor that the IND is on clinical hold, or 2. The FDA notifies the sponsor earlier that the clinical investigations in the IND may begin. 

For additional information on how to submit INDs, interested individuals may visit www.fda.gov/cdersbia and find the Investigational New Drug (IND) Applications webpage.

 

Return to "Research Investigational New Drug Applications – What You Need To Know" June 25, 2019 Issue