Good Clinical Practice: A Question & Answer Reference Guide - May 2018 - 31

GCP Regulations, Standards, and Guidelines for Clinical Research
therapeutic categories, the agency's discussions of these study examples may be instructive for other studies as
well. It is important to note, however, that just because a study is exempt from IND submission requirements does
not mean that the study is exempt from informed consent, IRB, or related GCP requirements.
1.40 Q. What are the IRB's responsibilities with respect to verifying the determination of whether an IND or
IDE is required for an FDA-regulated investigation?
A. The IRB's specific responsibilities vary, depending on the product that is the subject of the study; however,
in general, the IRB should ask the investigator whether he/she considered the need to obtain an IND or IDE and
the basis for any determination as to whether an IND/IDE is or is not needed. FDA regulations require sponsors
and clinical investigators to determine whether an IND/IDE is necessary for a particular study. The sponsor (or
sponsor-investigator of an individual investigator-initiated study) should be able to determine whether the IND
regulations apply to a planned clinical investigation as required under 21 CFR 312.2(a) or 21 CFR 812. If a
sponsor is uncertain, however, we recommend that the sponsor contact the appropriate review division (i.e., for the
therapeutic area being studied) in the appropriate FDA Center for advice about whether the IND/IDE regulations
apply. In an August 2013 guidance titled, "IRB Responsibilities for Reviewing the Qualifications of Investigators,
Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed," the FDA recommended
that the IRB ask the investigator/sponsor whether the need for an IND/IDE has been reviewed with FDA (if not
already included). They suggest that the IRB should request a copy of any letters or other documentation to support
any decision to proceed without an IND/IDE.
1.41 Q. Isn't in fact the sponsor or the sponsor-investigator's role to determine if an IND or IDE is needed for
the conduct of a study?
A. When reviewing a proposed study, IRBs should ask the clinical investigator whether an IND/IDE is or is not
required and the basis for the determination. If the sponsor or investigator has determined that an IND/IDE is
not needed, the IRB may request that the investigator provide a copy of any available documentation about the
need for an IND/IDE (e.g., letter from the sponsor or FDA, other basis for that determination). If during its initial
review of a study, the IRB questions whether an IND/IDE is necessary, but is unable to resolve this issue, the IRB
should follow its procedures for resolving controverted issues and delaying approval of the study until the matter is
resolved. The August 2013 guidance also suggests that the IRB may consider contacting the FDA directly to obtain
guidance on this issue.
1.42 Q. What other role is the IRB for in reviewing and approving a device research study?
A. The sponsor for a device study is responsible for making the initial risk determination, significant risk (SR) or
non-significant risk (NSR), and presenting it to the IRB. If the sponsor has determined that a device study is NSR,
the IRB must review the sponsor's determination. If the IRB disagrees with the sponsor's NSR assessment and
decides the study is SR, the IRB must inform the clinical investigator and, where appropriate, the sponsor. FDA is
also available to assist sponsors, investigators, and IRBs in making these determinations.
1.43 Q. One of the conditions of an IND exemption is that the sponsor or investigator does not intend to use
the results to support significant changes in a product's approved labeling. But does this mean that, if the
sponsor or investigator changes his or her mind, those results cannot later be submitted in a marketing
application?
A. Assuming that the sponsor or investigator acted in good faith in taking the IND exemption, those results can be
submitted in a marketing application. In the preamble to the 1987 IND regulations, the agency states that, "FDA
advises that a study that is conducted in good faith under the terms of the exemption in [FDA regulations] (i.e.,
without the filing of an IND) will later be acceptable to the agency in support of an IND or marketing application.
Therefore, where the agency finds that a study was conducted under the exemption on the reasonable belief that
each of the significant elements of the exemption applied, the FDA will not subsequently raise any objections to its
acceptance, assuming adequate guarantees of the ethical propriety and scientific validity of the study. On the other
hand, where there is evidence that the sponsor had no reasonable basis for concluding that a study should have
been exempted, FDA may take other regulatory action, as appropriate... As FDA is willing to discuss and advise

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2018