How to Submit an Investigational New Drug Application
Assemble an IND that supports a first-in-human trial and survives the review clock.
What a how-to is not
A how-to is SPEQ’s practitioner method, not a procedure. It does not replace your own SOP, it is not a validated approach, and the judgement calls in it belong to your quality unit.
An IND is a request for exemption from the rule that an unapproved drug may not be shipped across state lines. Practically, it is the package that persuades a reviewer that participants in the proposed trial are not exposed to unreasonable risk. The clock is short and it is not extended for an incomplete submission — it simply runs while the questions accumulate.
- 1
Decide what kind of application you are filing
Commercial development, an investigator-sponsored study, and expanded access are different submissions with different expectations. Filing an investigator-sponsored study on the template of a commercial programme buries the reviewer in content that has no bearing on the question in front of them.
- 2
Build the nonclinical package that supports the proposed exposure
The toxicology programme must support the dose, route, duration, and population you are proposing — not a generic package. Studies supporting safety must be conducted under good laboratory practice, and a deviation from it must be stated with its impact assessed rather than left for the reviewer to notice.
- 3
Describe chemistry, manufacturing and controls sufficient to assure identity, quality, purity and strength
The level of detail rises with the phase and with the duration of exposure. The reviewer’s question is whether the material a participant receives is what the protocol says it is, consistently — not whether the process is commercially ready.
- 4
Justify the starting dose and the escalation scheme
Show the derivation from the nonclinical data, the safety factor applied, and the stopping rules. A starting dose asserted rather than derived is the most reliable way to attract a clinical hold on a first-in-human protocol.
- 5
Include the protocol, the investigator brochure, and the investigator commitments
The brochure is what sites use to judge expectedness, so it must state what is known and what is not. Investigator qualifications and commitments are part of the submission, not site paperwork collected afterwards.
- 6
Wait out the review period before dosing, and keep the application current
The trial may not begin until the review period has elapsed without the application being placed on hold. After that, the obligation continues: new protocols, amendments, safety reports and annual reports all keep the application current, and an IND that is not maintained is not authorisation.
- !A toxicology package that supports a different duration, route, or population than the protocol proposes.
- !A starting dose asserted from precedent rather than derived from the nonclinical data with a stated safety factor.
- !Dosing initiated on the assumption that silence during the review period is approval before that period has elapsed.
- !The investigator brochure left unrevised as safety information accumulates, so sites judge expectedness against stale text.
How to Submit an Investigational New Drug Application: frequently asked questions
Common questions on submit an investigational new drug application.
Can a trial start as soon as the application is submitted?
No. A defined review period must elapse first, and dosing may begin only if the application has not been placed on clinical hold. Silence during that window is not permission to start early; it is the review still running.
Does every clinical investigation need an IND?
No — some studies of a lawfully marketed drug are exempt where they are not intended to support a new indication or a labelling change, do not involve a changed route, dose or population that significantly increases risk, and meet the other exemption conditions. The determination is documented reasoning, not an assumption, and getting it wrong means running an unauthorised trial.
What keeps the application current after it opens?
New protocols and amendments, safety reports, and an annual report describing progress and any changes to the risk picture. The application is a living authorisation, and a sponsor who files once and stops reporting has an inactive submission rather than a maintained one.