IND: The 30 Day Clock That Lets You Dose Humans
An IND is a request for an exemption. Federal law prohibits shipping an unapproved drug across state lines. An IND, governed by 21 CFR Part 312, exempts a specific investigational product from that prohibition so it can be shipped to clinical sites and given to humans.
FDA does not issue an approval letter. You submit, and if FDA does not object, you proceed.
The 30 day rule
You may begin the study 30 days after FDA receives the IND, unless FDA places it on clinical hold before then.
If FDA says nothing, you may start. A hold has to arrive inside the window to stop you, and FDA uses the window to review. Sponsors who file thin packages sometimes receive the hold on day 29.
Contents
- Form FDA 1571, the cover application.
- A general investigational plan: what you intend to study, and over what period.
- The investigator's brochure: everything known about the drug, written for the people who will administer it. Its accuracy matters beyond the filing, because "unexpected" in an IND safety report is defined against it.
- Protocols for each planned study.
- Chemistry, manufacturing and control (CMC) information: composition, manufacture, controls, and stability sufficient to assure identity, strength, quality and purity.
- Pharmacology and toxicology data supporting the conclusion that it is reasonably safe to begin human testing.
- Previous human experience, if any.
CMC and nonclinical gaps are the usual reason a first IND attracts a hold. The clinical plan is rarely the problem at this stage.
Commercial and non-commercial
Commercial IND. Intended to eventually support marketing. Must be submitted in eCTD format, mandatory since 5 May 2018.
Non-commercial IND. Investigator-initiated research, expanded access, emergency use. Exempt from the eCTD requirement.
An academic sponsor whose program turns commercial has a format migration to plan for, and it is easier before the lifecycle is long.
Types
- Investigator IND, filed by the physician who both directs administration and conducts the study.
- Emergency use IND, for a situation that does not allow time for the normal submission.
- Treatment IND, for a promising drug in serious conditions while the trial is ongoing.
Living with an open IND
An open IND carries continuing obligations: protocol amendments, information amendments, annual reports, and IND safety reports on the 7 and 15 day clocks.
Frequently asked questions
Does FDA approve an IND?
No. You may proceed 30 days after receipt unless FDA places the application on clinical hold. There is no approval letter.
What is the 30 day rule?
The waiting period between FDA receiving the IND and the sponsor being permitted to begin the study.
What most often triggers a hold on a first IND?
Insufficient nonclinical safety data and CMC deficiencies, rather than problems with the clinical protocol.
Do I need eCTD for my IND?
For a commercial IND, yes, since 5 May 2018. Investigator-initiated and expanded access INDs are exempt.
What is the difference between an IND and an NDA?
An IND exempts an investigational drug so it can be studied in humans. An NDA seeks approval to market the finished product.
How long does an IND stay open?
As long as the program runs. It carries annual reports and safety reporting throughout, and can be withdrawn or placed on inactive status.