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HRPP Policy - Expanded Access
About This Policy
- Effective date:
- 07/19/2018
- Last updated:
- 12/23/2024
- Policy Contact:
IU Human Research Protection Program (HRPP)
(317) 274-8289
irb@iu.edu
1.0 - Scope
The terms expanded access, compassionate use, and treatment use are often used interchangeably. This policy applies to expanded access for individual patient use (21 CFR 312.310 or 21 CFR 812.35(a)(2)), whether for emergency or non-emergency use, by a clinician at an Indiana University or IU-affiliated healthcare facility for which the IU Institutional Review Board (IRB) generally provides oversight.
This policy does not apply to off-label use of a test article approved by the Food and Drug Administration (FDA).
Back to top2.0 - Policy Statement
Per the FDA, “expanded access is a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.”
The expanded access for a single patient use can be either emergency use or non-emergency use.
For emergency individual patient use (21 CFR 56.102(d)), a clinician may use a test article without prospective IRB review and approval if the following conditions apply:
- The potential patient is in a life-threatening situation.
- No standard acceptable treatment is available.
- There is not sufficient time to obtain IRB approval.
The emergency use of a test article, other than a medical device, is not considered to be human subjects research but is a clinical investigation; the patient is a participant; and the FDA may require data from an emergency use to be reported in a marketing application.
Any subsequent use of the test article at the institution is subject to IRB review.
Expanded access for a single patient that is not emergency use, as described above, is considered to be non-emergency use. Prospective IRB review and approval is required for non-emergency individual patient use.
The following is applicable for both emergency use and non-emergency use. Note that FDA’s informed consent requirements (21 CFR 50) apply to all clinical investigations.
The clinician must obtain prospective, written informed consent from the patient or the patient's legally authorized representative (LAR) in accordance with IU HRPP Policy on Informed Consent.
An exception to the informed consent requirement may apply if both the treating clinician and a physician who is not otherwise associated with the use of the test article certify in writing all of the following:
- The patient is confronted by a life-threatening situation necessitating the use of the test article.
- Informed consent cannot be obtained because of an inability to communicate with or obtain legally effective consent from the patient.
- Time is not sufficient to obtain consent from the patient's LAR.
- No alternative method of approved or generally recognized therapy is available that provides equal or greater likelihood of saving the life of the patient.
If, in the clinician's opinion, immediate use of the test article is required to preserve the life of the patient and time is not sufficient to obtain the independent determination regarding exception to the informed consent requirement in advance, the determination shall be made by the clinician and, within five (5) business days after the use of the article, be reviewed and evaluated in writing by a physician who is not participating in the use of the test article.
During regular business hours, the clinician should contact the HRPP and consult with staff regarding whether an existing IRB-approved protocol would allow use of the test article, whether an Investigational New Drug (IND) or Investigational Device Exemption (IDE) from the FDA is needed, and whether the situation allows for sufficient time to obtain IRB approval.
Outside of regular business hours, or if the HRPP is not available, the clinician may use the test article under this policy, carefully documenting the following:
- The conditions for emergency use specified in 2.0 are met.
- Consent was obtained and documented in accordance with the IU HRPP Policy on Informed Consent, unless the exception from informed consent requirements described in 2.1 above applies.
Reporting to the IRB
Use of a test article under this policy must be reported to the IRB within five (5) business days. The clinician must submit notification via a Kuali Protocols Emergency Use submission and provide the following information:
- A full description of the situation, including justification for the emergency use;
- A full description of the test article, including the trade name, generic name, chemical name, and/or device name, the IND or IDE number, and name of sponsor/manufacturer;
- A full description of the procedure(s) employed; and
- A description of the consent process used, including an unsigned copy of the informed consent document.
- If an exception from informed consent was utilized, the clinician must provide documentation addressing the points described in 2.1 above.
When the HRPP receives notification of an emergency use that has taken place, an HRPP Assistant or Associate Director or the University Director, review the report to determine if the use complied with FDA and institutional requirements. If requirements were met, an acknowledgement letter is sent to the clinician. If it is determined that requirements were not met, the matter is handled according to the noncompliance procedures delineated in the IU HRPP Policy on Reportable Events.
Approval from both the FDA and IRB is required prior to use. The clinician must complete and submit appropriate forms to the FDA for approval of IND or an IDE, as applicable.
When completing an IND application (Form FDA 3926) for this purpose, clinicians should check the box in Field 10.b. Once the IND is approved by the FDA with the field 10.b checked, IU IRBs may review the IRB application as a single-member review process.
When submitting an IDE request for this purpose, the clinician may request, in writing, a similar exception to the convened board review requirement, allowing the use of a single-member review process.
Reporting to the IRB
The IRB application should be submitted consistent with the IU HRPP Policy on IRB Review Process. It should include the request to the FDA for the IND or IDE approval, as applicable. The IRB application will be reviewed by HRPP staff for completeness.
For research subject to an IND, an expedited review process under a single-member reviewer may be utilized if 10.b is checked in the IND application. For research subject to an IDE, the FDA must confirm that a single-member review can be allowed in lieu of a convened board review. An IRB Chair or designee may serve as the single-member reviewer. If the IRB application is not eligible for single-member review, it will be assigned to an IRB meeting for review and appropriate action.
Upon approval of the IRB application, subsequent amendments and continuing reviews should be submitted to the IRB consistent with the IU HRPP Policy on IRB Review Process. Amendments and continuing reviews may be reviewed by a single-member reviewer if they meet the criteria described in the paragraph above.
4.0 - Sanctions
Individuals found to be in violation of this policy may be subject to sanctions relating to their participation in research with human subjects, up to and including permanent suspension or debarment from engaging in research with human subjects at Indiana University.
Back to top5.0 - History
Policy title revised from “Emergency Use of Investigational Test Articles” to “Expanded Access of Investigational Test Articles for Single Patient Use.” Scope (Section 1.0), Policy Statement (Section 2.0), and Procedures (Section 3.0) revised to describe and delineate between emergency use and non-emergency use of expanded access for a single patient. Non-emergency use procedures describe when a single-member review may be utilized. Additional citations included in Related Information (Section 6.0).
Back to topRegulatory References
- AAHRPP Standards
- Element I.7.C
- 21 CFR 50.23(a)
- 21 CFR 56, especially 56.102(d), 56.104(c)
- 21 CFR 312, especially 312.310
- 21 CFR 812, especially 812.35(a)(2)
- 45 CFR 46.116(j)
- FDA Guidance: Emergency Use of an Investigational Drug or Biologic-Information Sheet
- FDA Guidance: Frequently Asked Questions About Medical Devices
- FDA Guidance: Individual Patient Expanded Access Applications: Form FDA 3926
- FDA Guidance:Institutional Review Board (IRB) Review of Individual Patient Expanded Access Submissions for Investigational Drugs and Biological Products
- FDA Guidance: Waiver of IRB Requirements for Drug and Biological Product Studies
7.0 - Definitions related to this policy
clinical investigation, device, drug, informed consent, institutional review board (IRB), investigational biologic/drug/device/test article, investigational device exemption, investigational new drug application, IRB-approved protocol, legally authorized representative (LAR), life-threatening, noncompliance, sponsor, test article, written/in writing
View All Abbreviations and Definitions
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