In October 2015 FDA released a clarification regarding IND application requirements. Their clarification is regarding queries and confusions amongst sponsors, investigators and RECs when do they need to apply for IND.
Those who have applied for IND are probably aware already that IND stands for Investigational New Drug Application, which was implemented in order to protect safety and rights of clinical trials participants and assure data quality that will allow proper evaluation of new drugs.
So when IND is not needed?
1. Research involving marketed drugs – In order the clinical trial not to require IND application all the listed below criteria should be met:
- The drug product is lawfully marketed in the United States.
- The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication and there is no intent to use it to support any other significant change in the labeling of the drug.
- In the case of a prescription drug, the investigation is not intended to support a significant change in the advertising for the drug.
- The investigation does not involve a route of administration, dose, patient population, or other factor that significantly increases the risk (or decreases the acceptability of the risk) associated with the use of the drug product (21 CFR 312.2(b)(1)(iii)).
- The investigation is conducted in compliance with the requirements for review by an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR part 50).
- The investigation is conducted in compliance with the requirements of § 312.7 (i.e., the investigation is not intended to promote or commercialize the drug product).
2. Bioavailability or Bioequivalence Studies in Humans – the following criteria should be met in order the study not to require IND application:
- The drug product does not contain a new chemical entity (21 CFR 314.108), is not radioactively labeled, and is not cytotoxic.
- The dose (single dose or total daily dose) does not exceed the dose specified in the labeling of the approved version of the drug product.
- The investigation is conducted in compliance with the requirements for review by an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR part 50).
- The sponsor meets the requirements for retention of test article samples (21 CFR 320.31(d)(1)) and safety reporting (21 CFR 320.31(d)(3)
3. Radioactive Isotopes – the following criteria should be met for studies that do not require IND:
(1) it involves basic research not intended for immediate therapeutic, diagnostic, or similar purposes, or otherwise to determine the safety and efficacy of the product,
(2) the use in humans is approved by a Radioactive Drug Research Committee (RDRC) that is composed and approved by FDA,
(3) the dose to be administered is known not to cause any clinically detectable pharmacological effect in humans, and
(4) the total amount of radiation to be administered as part of the study is the smallest radiation dose practical to perform the study without jeopardizing the benefits of the study and is within specified limits.
Are there any special cases?
1. Endogenous compounds (bradykinin, histamine, angiotensin, etc) – in some cases where endogenous compounds are used to study physiological reaction, disease or mechanism of action and not intended as treatment IND application is still required because endogenous compound intent to affect structure or function of the body. Such studies require IND unless they meet the criteria to be excluded.
2. Live organisms (bacteria, viruses, fungi, etc.) – it is similar case with clinical trials that intend to study disease pathogenesis and body response. Although again they do not intend to treat the participants they affect structure or function of the body so they will require IND application.
3. Cosmetic products – they do not require IND application unless they affect the structure or function of the body or to prevent, treat, mitigate, cure, or diagnose a disease.
Always refer to FDA latest guidelines if you in doubts about IND application. You can find more information here:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
Author: Olga Peycheva
Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe.
Originally published on 3 May 2016