Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff: Guidance on Informed Consent for In Vitro Diagnostic Device

Thursday April 8, 2010

Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff: Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable

Name: Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff: Guidance on Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable

Status of Guidance: Final Guidance

Guidance Released: April 25, 2006

Link to Guidance: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM071265.pdf

Audience: This guidance was created for in vitro diagnostic manufacturing companies (sponsors), institutional review boards (IRBs), clinical investigators, and the staff of the US Food and Drug Administration (FDA).

Definition of Terms Used in this Guidance:
Agency: The FDA.
In vitro: This refers to tests performed outside of the patient’s body, for example, tests that are performed on a patient’s blood in a laboratory.
In vitro diagnostic products: These are the reagents (chemicals), instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, lessen the severity of, treat, or prevent disease or its negative after-effects. In vitro diagnostic products are intended for use in the collection, preparation, and examination of specimens taken from the human body.
Leftover specimen: This is the remaining portion of a human specimen collected for routine clinical care or analysis that would otherwise have been discarded.
Not individually identifiable: A specimen is considered not individually identifiable when the identity of the subject is not known to or may not readily be ascertained by the investigator or any other individuals associated with the investigation, including the sponsor.
Specimen repository: This is a common site for storage of collections of human biological specimens available for study.

Laws and Regulations Referenced:
1. 21 CFR 10.115: Good guidance practices
2. 21 CFR part 50: Protection of human subjects
3. 21 CFR 50.23(a): Exception from general requirements of informed consent of human subjects
4. 21 CFR 50.24: Exception from informed consent requirements for emergency research
5. 21 CFR part 56: Institutional Review Boards
6. 21 CFR 809.3(a): In vitro diagnostic products for human use definition
7. 21 CFR 812.2(c)(3): Exempted investigations of diagnostic devices
8. 21 CFR 812.3(p): Definition of “subject”
9. Section 520(g) of Federal Food, Drug, and Cosmetic Act (the Act), 21 USC 360j(g): Exemption for devices for investigational use
10. 44 USC 3501-3520: Paperwork Reduction Act

Rationale: The FDA issued this guidance to notify in vitro diagnostic manufacturing companies (sponsors), IRBs, clinical investigators, and agency staff that under certain circumstances it intends to exercise enforcement discretion with respect to its current regulations governing the requirement for informed consent when human specimens are used for FDA-regulated in vitro diagnostic (IVD) device investigations. The FDA requires that informed consent be obtained from human subjects, except in limited emergency circumstances specified in the regulations (see 21 CFR 50.23(a) and 50.24), before specimens can be used in FDA-regulated research. The regulations requiring informed consent when human specimens are used for IVD device research have created confusion and difficulty for persons developing IVD devices. In fact, many clinicians, research hospitals, and IVD device companies have viewed the FDA requirement for informed consent for IVD device studies using leftover specimens as unnecessary for the protection of human subjects as well as an overly burdensome and costly requirement.

Summary: This guidance applies only to those IVD device studies that use leftover specimens that are not individually identifiable, are regulated by the FDA, and are exempt from most requirements of the Investigational Device Exemptions (IDE) regulation. The FDA believes that it is possible in certain circumstances for IVD device studies to be conducted using leftover specimens obtained without informed consent while protecting the human subjects who are the source of such specimens. The IVD device studies do not pose new medical risks to subjects because the specimens have already been collected from the subjects. Additionally, no risks from erroneous test results are presented because the results of the testing in the IVD device studies are not used for clinical management of the subject. Finally, privacy risks are mitigated by limiting the applicability of this guidance to specimens that are not identifiable.

Resulting Recommendations:
The FDA will exercise human subject informed consent enforcement discretion when an IVD device investigation is performed and all of the following are true:
1. The study meets the IDE criteria presented in 21 CFR 812.2(c)(3).
2. The study uses any of the following types of specimens: leftover specimens, specimens obtained from specimen repositories, or leftover specimens that were previously collected for other research purposes.
3. The specimen is not individually identifiable. This means that the identity of the subject is not known and may not easily be determined by the investigator or any other person associated with the study, including the sponsor.
4. It is permissible for the specimens to be accompanied by clinical information as long as the clinical information does not make the identity of the subject available to the investigator or any other person associated with the study, including the sponsor.
5. The people conducting the study are not the same people who are caring for the patients and those people caring for the patients do not share information about the patients with the people who are conducting the study.
6. The specimens are provided to the investigator without any information that would identify the subjects who provided the specimens. The supplier of the specimens must have established policies and procedures to prevent the release of the subjects’ personal information.
7. The study has been reviewed by an IRB.

Impact:
This guidance will eliminate the confusion regarding the application of informed consent requirements to IVD device studies. It will also eliminate the concerns about unnecessary obstacles to IVD device product development, thereby enabling the efficient development of IVD devices in a manner consistent with the values of human subject protection.