1. Opening an IND: Investigator Perspective
Michael Cohen-Wolkowiez, MD PhD
Pediatric Trials Network
Professor of Pediatrics, Duke University

2. What is a Drug?
A drug is anything that meets the definition of a drug per the FD&C Act (201(g)(1)). . .
“. . .articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals. . .”
“…a substance (other than food) intended to affect the structure or any function of the body”
Note: This definition includes“…compounds administered to blunt or provoke a physiological response or to study the mechanism of action or metabolism of a drug.”
As the name implies, INDs are only needed for studies that involve the use of a drug.
Drugs are NOT just products intended for therapeutic purposes.
Includes biologics
Slide courtesy of Duke Office of Regulatory Affairs and Quality

3. What is an Investigational Drug?
An article that is not lawfully marketed in the US as a drug, OR
An article that is lawfully marketed in the US as a drug that is not used according to the approved label (including a new combination of approved drugs)
Note: The practice of medicine allows a physician to use any lawfully marketed drug without prior regulatory approval.
Two types
In the context of a clinical investigation
Will talk more about ‘lawfully marketed’ in a few slides.
NOTE: doesn’t need to be used according to its approved label in the practice of medicine.
Example: A drug for seizures but there’s evidence that it may be effective for migraines, a physician can prescribe it for migraines without any regulatory oversight (no IND) – unless they’re starting to collect data and administering the product per a clinical protocol > Then the drug becomes an investigational drug.

4. What is an Investigational New Drug Application (IND)?
An IND is a regulatory submission to the FDA that permits the clinical investigation of a drug.
An effective IND allows:
An investigational drug (or biologic) to be used in a clinical investigation.
A drug to be shipped lawfully for the purpose of conducting clinical investigations.
Not all clinical investigations using investigational drugs require an IND.
The term “drug” also includes biologics. IND is for both drugs and biologics.
Such authorization must be secured prior to interstate shipment of any new drug that is not lawfully marketed in the US as a drug for the purpose of conducting clinical investigations.
Current federal law requires that a drug must be the subject of an approved marketing application before it is transported or distributed across state lines.

5. Definitions: Categories of INDs
Commercial IND
Ultimate goal is to obtain marketing approval
Research IND
Goal is publication
Generally sponsored by individual investigators, academic institutions, and non-profit entities
Labeling changes
Goal: Commercialize a product.
**Requirements for the IND content and format are the same regardless of if the IND is a commercial or research IND.

6. Does My Clinical Study Require an IND?
Test Article
Not legally marketed in the US as a drug
Investigational Drug
Requires an IND
We’re going to use this flowchart to walk through the decision making process for determining if a study requires an IND.
Unlike clinical studies with devices, it doesn’t matter if you’re testing safety or effectiveness of the drug. If you are conducting a clinical investigation with a product not lawfully marketed in the US as a drug, it will require an IND.
(Some exemptions that we will discuss as we go…dietary supplement structure/function studies, radiolabeled drugs)
Clinical investigations using a product that is not lawfully marketed in the US as a drug require an IND.

7. Does My Clinical Study Require an IND?
Test Article
Not legally marketed in the US as a drug
Legally marketed in the US as a drug
Investigational Drug
Lawfully Marketed Drug
Requires an IND
Need an IND?
On label = no IND required
Off-label = It depends! Your study may be exempt of requiring an IND if your study meets the exemption criteria that we’re going to cover next.
Off-label
On-label
IND not required*
Does the study meet the IND exemption criteria?
* Assuming no marketing application or change in advertising is planned

8. IND Exemption Criteria
A clinical investigation of a drug product that is lawfully marketed in the United States is exempt from requiring an IND if all five criteria are met:
The study is not designed to support approval of a new indication or a change in label.
The study is not intended to support a significant change in the advertising for the product.
The study does not involve a route of administration, dosage level, patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug.
The study is conducted in compliance with the IRB and informed consent regulations.
The study is conducted in compliance with regulations regarding promotion for investigational drugs.
For studies using lawfully marketed drugs…

9. IND Advantages to the Investigator
Mechanism to change labels
Dissemination of information outside of publication
Protocol review and feedback by FDA
IRB compliance
Requirement for funding agencies (government and foundations)
Regulatory science training

10. IND Disadvantages to the Investigator
Need for institutional support for submission and maintenance
Protocol review and feedback by FDA?
Formulation questions may require additional work prior to clinical investigation
Increased burden for safety reporting
Data management system?

11. Acknowledgements
NICHD – Pediatric Trials Network