Key Concepts of IND in Clinical Investigations

Sponsor

An individual, company, academic institution, or organization that takes responsibility for and initiates a clinical investigation.

Investigator

An individual under whose immediate direction a drug is administered or dispensed to subjects.

Sponsor-Investigator

An individual who both initiates and conducts an investigation (combines both sponsor and investigator roles).

Commercial IND

An IND submission with the ultimate goal of obtaining marketing approval, typically submitted by pharmaceutical or biotech companies.

Research/Non-commercial IND

An IND that is primarily research-driven rather than seeking marketing approval, often submitted by academic institutions.

Emergency Use IND

An IND used only in life-threatening situations that don't allow time for standard submission and review, with the IND submitted as soon as possible after use.

Exploratory IND

An early Phase 1 study involving limited human exposure with no therapeutic intent, requiring less preclinical data.

Treatment IND

An IND used to make promising new drugs available to desperately ill patients early in development when they don't qualify for clinical trials.

Main components of an IND application

Cover Sheet (Form FDA 1571), Table of Contents, Introductory Statement, Investigator's Brochure, Clinical Protocol, Chemistry/Manufacturing/Control Information, Pharmacology/Toxicology Information, Previous Human Experience, Additional Information.

Pre-IND meeting

The planned content of the application, potential issues, requirements for specific therapeutic areas, and strategy for clinical development.

Primary objectives of the IND process

1) Ensure safety and rights of subjects in all phases; 2) Help assure scientific quality of safety and effectiveness evaluation in Phase 2-3.

FDA review areas in an IND application

Safety, medical/clinical aspects, chemistry, pharmacology/toxicology, and statistical considerations.

Criteria for IND exemption

All six criteria must be met.

Three criteria for IND exemption

(Specific criteria not provided in the notes, but three examples could be: 1) The study is not intended to support a commercial application; 2) The study does not involve significant risk to subjects; 3) The study is conducted in compliance with applicable regulations.)

IND safety report timeline

Within 15 calendar days of receiving the information.

Reporting timeline for unexpected fatal or life-threatening experiences

No later than 7 calendar days of receiving the information.

Who informs the sponsor about adverse effects

The investigator.

Who notifies FDA about serious and unexpected adverse experiences

The sponsor.

Protocol Amendment in an IND

A submission to change the protocol, add a new protocol, or add a new investigator that requires FDA submission and IRB approval prior to implementation.

Information Amendment in an IND

An update to non-protocol information such as clinical data, pharmacology/toxicology data, or CMC information.

Annual report submission for ongoing IND

Within 60 days of the anniversary date that the IND went into effect.

Requirements before implementing a protocol amendment

FDA submission and IRB approval are both required before implementation.

Responsibilities of an IND sponsor

Select qualified investigators, ensure protocol compliance, monitor the investigation, maintain IND, report adverse events, maintain records, control drug distribution.

Responsibilities of an investigator in an IND study

Personally supervise the investigation, follow protocols and regulations, protect subject rights and safety, obtain informed consent, report adverse events, ensure IRB approval, maintain accurate records.

Primary concern of the investigator regarding study subjects

The investigator's primary responsibility is to protect the rights, safety, and welfare of the study subjects.

Difference between a superiority trial and a non-inferiority trial

A superiority trial aims to demonstrate that a drug is better than the comparator, while a non-inferiority trial aims to show the drug is not worse than the comparator by a pre-specified margin.

Changing from a superiority trial to a non-inferiority trial

Yes, but it requires regulatory approval, and the change must be made before data analysis and cannot be reversed afterward.

Importance of timing in safety reporting

Delays in reporting serious adverse events could put subjects at risk, violate regulations, and potentially lead to clinical holds or other regulatory actions.