A clinical investigation involving a drug or biological product, other than the use of a marketed drug or biological product in the course of medical practice, must be conducted under an investigational new drug application (IND), unless the clinical investigation is exempt from the IND requirements of 21 CFR 312.
Investigational drugs or biological products must be stored appropriately and used only in approved research protocols under the direction of approved investigators.
Drug means articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. Drug also means articles (other than food) intended to affect the structure or any function of the body. In general, the term "drug" includes therapeutic biological products.
Biological product means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. Biological products include, among other products, bacterial vaccines, allergenic extracts, gene therapy products, growth factors, cytokines, and monoclonal antibodies.
Test article means any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the Public Health Service Act.
Clinical investigation means any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. An experiment is any use of a drug (whether approved or unapproved) except for the use of a marketed drug in the course of medical practice.
Investigational new drug means a new drug or biological product that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. The terms "investigational drug" and "investigational new drug" are synonymous.
Sponsor means a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization.
Investigator means an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the drug is administered or dispensed to a subject). In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team.
Sponsor-investigator means an individual who both initiates and conducts an investigation and under whose immediate direction the investigational drug is administered or dispensed. The term does not include any person other than an individual.
When the research involves a drug or biological product, the Principal Investigator (PI) will provide information on the drug or biologic product in the initial application via iRIS, including but not limited to:
- FDA determination status/issuance letter
- IND Number
- Rationale for IND exemption, if PI determines that an IND is not required
- Package insert or investigator brochure for all drugs and/or biological products involved in the study
- If the source is not a FDA licensed facility, details regarding the purity, quality, stability, and sterility of the test article
- Plan for storage, dispensing, preparation and administration of test article
- List of investigators authorized to prescribe
Confirmation of Drug Documents and Rationale:
For each investigational drug or biological product involved in the study, IRB staff will ensure that a package insert or investigator brochure has been uploaded to iRIS. If the investigator believes that the study is IND exempt, then IRB staff will ensure that a justification for IND exemption has been included in the IRB application under Drug Details.
Confirmation of IND Number:
If the PI has provided an IND number, then the regulatory reviewer will confirm that the IND number is valid by any of the following methods:
- For studies in which the UTHealth PI is not the sponsor-investigator (that is, there is an industry sponsor that holds the IND, or the study is multi-site and an institution other than UTHealth is the lead site that initiated the study and holds the IND), at least one of the following must be submitted to the IRB:
- Sponsor protocol documenting the IND number.
- Written communication from the sponsor documenting the IND number.
- Written communication from the FDA documenting the IND number.
- For studies in which the UTHealth PI is the sponsor-investigator (that is, the UTHealth PI holds the IND), one of the following must be submitted to the IRB:
- If the protocol is submitted with an initial IND application, written communication from the FDA documenting the IND number.
- If the protocol is submitted to an existing IND, documentation that the protocol has been submitted to FDA as an “IND Protocol Amendment – New Protocol,” in addition to written communication from the FDA documenting the IND number.
Review for IND Exemption:
When research involves a drug or a biologic and there is no IND, the convened IRB will determine if the IND exemption criteria are met. The regulatory reviewer will enter recommendations to iRIS under Review Checklist and Comments. CPHS may ask that the UTHealth PI request an IND determination from FDA.
A clinical investigation of a drug is exempt from the IND requirements if all of the following exemption criteria are met:
- The drug is lawfully marketed in the United States.
- The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug.
- If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product.
- The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use 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 investigation is conducted in compliance with the marketing limitations described in 21 CFR 312.7 (i.e., the investigation is not intended to promote or commercialize the drug product).
- The investigation does not involve an exception from informed consent (EFIC). (A clinical investigation involving an exception from informed consent (EFIC) for emergency research under 21 CFR 50.24 is not exempt from the IND requirements.)
A clinical investigation involving the use of placebo is exempt if it does not otherwise require submission of an IND application.
A clinical investigation involving an in vitro diagnostic biological product (blood grouping serum; reagent red blood cells; anti-human globulin) is exempt if the diagnostic test is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established diagnostic product or procedure and the diagnostic test is shipped in compliance with 21 CFR 312.60.
INDs must be submitted for certain bioavailability or bioequivalence studies in humans, per the requirements of 21 CFR 320.31.
Review of Plan for Storage and Dispensing of Drug:
CPHS shall ensure that the PI’s plan for control of investigational material is appropriate. In general, pharmacy service should be used for storage and dispensing of the investigational material. CPHS may approve of a plan to store and dispense investigational material by an experienced investigator or study coordinator in certain situations such as industry sponsored research with a plan for monitoring.
The regulatory reviewer will enter recommendations in iRIS under Review Checklist and Comments. If CPHS determines that an IND is required, then IRB staff will communicate this to the PI, and CPHS approval will not be granted until the PI submits written evidence that FDA has determined the study may proceed under the IND or submits written communication from FDA that an IND is not required.
IND Determination When UTHealth PI is Not the Sponsor-Investigator: If the UTHealth PI is not the sponsor-investigator [that is, the study is multi-site and an institution other than UTHealth is the lead site], then the IRB at the lead site will make an IND exemption determination; however, UTHealth IRB may or may not agree with this determination and may require the PI to seek FDA’s determination.
FDA Determination of IND Required After IRB Determination of IND Exempt: In the event the FDA determines that an IND is required after UTHealth IRB determined the study to be IND exempt, the IRB will follow guidance from FDA on whether to continue or suspend the study.
APPLICABLE REGULATIONS AND GUIDANCE
- FDA Investigational New Drug Application
- FDA Guidance for Clinical Investigators, Sponsors, and IRBs – Determining Whether Human Research Studies Can Be Conducted Without an IND – Sept 2013
REFERENCES TO OTHER SOP
- Regulatory Review
- Study Drug Panel – IRB Application Form
If you find errors in this document, contact firstname.lastname@example.org
Investigational Drugs and Biological Products
Executive Director, Research Compliance
1 Aug 2008
1 Jan 2009, 1 Aug 2011, 1 Jun 2016, 19 Jan 2018, 1 Jun 2021
CPHS HELPLINE 713-500-7943
iRIS HELPLINE 713-500-7960
UTHealth’s Compliance Hotline (1-888-472-9868)
IRB OFFICE HOURS Thursdays from 1 to 4pm, via the Teams Room at this link
How can we improve this site?