Quorum Review's October 2013 Institution Bulletin includes Letter from CEO, Cami Gearhart, JD, addressing the delicate balance of protecting privacy and future research, as well as Quorum's insights on recent FDA guidance regarding how IRB's evaluate clinical trials as well as determining whether or not an IND is needed for a particular drug study.

1. October 17, 2013 | Volume 3, Issue 4
Institutional Bulletin
Letter from the CEO
Henrietta and David Lacks
Courtesy of the Lacks Family
The research community continues to struggle with conflicting
values: the benefits of sharing data, the gains of genetics research
and the importance of respecting an individual’s privacy. These
values collided this past March, when a German researcher
released on-line the complete genomic sequence of the HeLa cell
line. The researcher had not violated any rules or regulations.
Nevertheless, the family of Henrietta Lacks, whose cancer cells
were the genesis of the HeLa cell line, raised concerns about the
very personal information that could be revealed by the genomic
sequence.
In response to the resulting storm of controversy the researcher withdrew the sequence from the public database.
And as reported by Dr. Francis Collins in the August issue of Nature, the NIH and the Lacks family have come
to an agreement by which the full HeLa sequence data will be maintained in a controlled-access database and
released only with the approval of a panel that includes members of the Lacks family.
While this agreement resolves one family’s concerns, IRBs are left to find acceptable resolutions on a day-today basis between individual privacy interests and researchers’ requests to conduct unspecified future research
on genetic material. Quorum Review looks forward to working with the research community in working out
resolutions. We’re honored to have the privilege to work with you and your research teams; please let us know if
we can be of further assistance.
Sincerely,
Cami Gearhart, CEO
Quorum Review IRB
1601 Fifth Avenue, Suite 1000 | Seattle, Washington 98101
T 206.448.4082 | F 206.448.4193 | QuorumReview.com
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2. October 17, 2013 | Volume 3, Issue 4
FDA Guidance:
Provides Clarification Regarding IRB Evaluation of Clinical Trials
A new guidance published by the U.S. Food and Drug
Administration (FDA) aims to clarify the responsibilities of
institutional review boards (IRBs) in evaluating investigators
and research sites. This guidance, IRB Responsibilities for
Review the Qualifications of Investigators, Adequacy of Research
Sites and the Determination of Whether an IND/IDE is Needed,
is the finalized version of the Draft guidance of the same
name, issued in 2012, and not much has changed from the
original draft.
The guidance provides direction to IRBs as to their role
in evaluating three aspects of clinical trials submitted for
review: (1) the qualifications of the clinical investigator;
(2) the adequacy of the research site, and (3) the necessity
of an IND or IDE for a given study. The FDA advises that
although these aspects of a trial are viewed primarily as
sponsor responsibilities, IRBs have responsibilities related to
these activities as well. The FDA also recommends that IRBs
have written procedures addressing the decision-making
process for each of these aspects of evaluating clinical trials.
Qualifications of the Clinical Investigator
When evaluating a proposed clinical investigator, the FDA
advises that IRBs should keep in mind their responsibility to
“ascertain the acceptability of the proposed research in terms
of institutional commitments and regulations, applicable
law, and standards of professional conduct and practice”1 as
well as the requirement to “determine that risks to subjects
are minimized and reasonable in relation to anticipated
benefits.”2
In order to comply with these requirements, the IRB should
gather information about the investigator and applicable
institutional policies. The FDA suggests that the IRB
could rely on a statement from the institution that a given
investigator met the requirement of a hospital that only
credentialed staff may conduct research.
In cases where the IRB is not affiliated with the institution,
the IRB should conduct its due diligence, and may take
some or all of the following steps as part of its review of
investigators:
„„ Reviewing the curriculum vitae of the investigator
„„ Reviewing the curriculum vitae of the sub-investigators
and other necessary staff
„„ Obtaining verification of professional associations and
medical licensure
„„ Reviewing relevant publications
„„ Obtaining documentation of the investigator’s
training in good clinical practice
In cases where the research involves higher risks, vulnerable
subjects, or novel technologies, the FDA expects the IRB
review may be adjusted
to include review of
experience, or training
with the test article or
study-related procedures.
Special attention is
expected when reviewing
research involving a
sponsor-investigator;
that is outside of the
investigator’s area of expertise; or that has design features
or other characteristic(s) that may significantly increase
potential risk to subjects.
(continued)
1 21 CFR 56.107(a).
2 21 CFR 56.111.
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3. October 17, 2013 | Volume 3, Issue 4
Evaluating the Adequacy of the Research Site
Implications for Quorum Review IRB
The FDA also provides guidance for IRBs when evaluating
research sites. The expectation that the IRB reviews the
acceptability of the research is also invoked here. Although
IRBs may rely on previous experience with a clinical
investigator or institution, the FDA again indicates that
when the IRB has no affiliation with the research site it
likely will need to obtain specific information about the
research site, including:
Quorum Review has evaluated this guidance and the
FDA recommendations are in-line with existing Quorum
procedures and policies. Quorum’s clients should not expect
to see any changes to submission requirements or other
policies as a result of this guidance.
„„ An explanation of staffing
„„ A description of equipment that may be needed
to conduct the research or in the event of an
emergency
„„ Any other information describing resources
relevant to the research
Determination of Whether an IND or IDE is
Required
On the issue of whether an IND is required, the guidance
advises that the IRB ask the investigator if an IND or IDE is
required and the basis for their determination on the issue.
For drug and biologics studies, the IRB may request that
the investigator provide a copy of available supporting
documentation, if they indicate they have not obtained an
IND. Such documentation may include a letter from the
sponsor or the FDA. If the IRB has questions about whether
an IND is required, the IRB is expected to delay approval of
the study until the matter is resolved.
For Device studies, the IRB is expected to review the
sponsor’s determination that a device study does not require
an IDE because it is either nonsignificant risk (NSR) or
exempt. In the event the IRB disagrees with the sponsor’s
determination, it should inform the investigator and
sponsor.
When Performance Matters
Choose Quorum Review
Working with Institutions to
Achieve Great Things
Quorum Review personalizes the
IRB approach for your specific
research studies with customized
coversheets and model consent
forms that utilize language
preferences. We understand and
recognize your needs and we are
here to facilitate your research
process.
• Personalized Account
Manager
• OnQ online
document portal
• Diverse training options
• Fast turnaround times
• Phase I-IV review
• Customized approach
Learn more about Quorum’s
customized processes for the ethics
review of institutional research at:
www.quorumreview.com/institutions
3

4. October 17, 2013 | Volume 3, Issue 4
New FDA Guidance for Clinical Investigators, Sponsors, and IRBs:
Investigational New Drug Applications (INDs) – Determining Whether Human Research
Studies Can Be Conducted Without an IND
The Food and Drug Administration (FDA) published a draft
guidance document in September 2013 on determining
whether human research studies can be conducted without
an Investigational New Drug Application (IND).1 This
guidance document is intended to address common
questions posed by clinical investigators, sponsors, and IRBs
when assessing whether an IND is required for a drug study.
Please note this guidance is intended to clarify existing
regulations under 21 CFR part 312, and does not address
devices subject to 21 CFR part 812 (the IDE regulations).
Overview
The FDA receives many questions about whether the IND
requirements in part 312 apply to:
„„ Clinical investigations using marketed drugs
„„ Bioequivalence/bioavailability studies
„„ Studies using radiolabeled or cold isotopes
„„ Studies using dietary supplements or foods
„„ Studies using endogenous compounds
„„ Pathogenesis studies using modified organisms
„„ Studies using wild-type organisms in challenge models
„„ Studies that do not have a commercial purpose2
Generally, any drug study must follow the IND requirements
under 21 CFR part 312 if:
„„ The research involves a drug as that term is defined
in section 201(g)(1) of the Federal Food, Drug, and
Cosmetic Act (the FD&C Act) (21 U.S.C. 321(g)(1));
1 Investigational New Drug Applications (INDs) – Determining Whether
Human Research Studies Can Be Conducted Without an IND, Food and
Drug Administration, September 2013, available at: http://www.fda.
gov/downloads/Drugs/Guidances/UCM229175.pdf.
2 Id. at 2.
„„ The research is a clinical investigation as defined in
the IND regulations (21 CFR 312.3);
„„ The clinical investigation is not otherwise exempt
from the IND requirements in part 31;3
Marketed Drugs
An IND will be required for a clinical investigation of
a marketed drug unless all of the exemption criteria in
§312.2(b) are met:
„„ The investigation is not intended to be reported
to 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 institutional review set forth
in part 56 and with the requirements for informed
consent set forth in part 50; and
„„ The investigation is conducted in compliance with
the requirements of 312.74
3 Id. at 2
4 Id. at 4-5
(continued)
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5. October 17, 2013 | Volume 3, Issue 4
Bioavailability or Bioequivalence Studies
Additional Topics Covered
An IND is not required for bioavailability or bioequivalence
studies if the following criteria are met:
The guidance further discusses when an IND is required
for clinical investigations of radioactive and cold isotopes,
endogenous compounds, live organisms, cosmetics, foods,
other studies intended to support a health claim, and
research with noncommercial intent.7 The guidance also
discusses other frequently asked questions.8
„„ 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));5
Sponsor’s Role
The sponsor or sponsor-investigator is responsible for
determining whether an IND is required. The FDA requests
the sponsor contact the appropriate review division within
the FDA to determine whether the IND regulations apply if
the sponsor has any uncertainty if an IND is required.9 The
guidance provides detailed information how to contact the
FDA and the process that will be followed for inquiries.
Dietary Supplements
An IND may be required for studies for dietary supplement
if the clinical investigation is intended to evaluate the
supplement’s ability to diagnose, cure, mitigate, treat,
or prevent a disease. A dietary supplement will not be
considered a drug and is not subject to the IND regulations
if the intended use for which it is marketed is only to affect
the structure or any function of the body.6
Contact Quorum Review
Interested in learning more about Quorum Review?
Our Institutional Team is ready to answer your inquiries
regarding your organization’s specific institutional IRB
needs.
Nancy Jane Earnhardt
Institutional Specialist - East
nearnhardt@quorumreview.com
T| 919-930-5198
Lyndsey Broerman
Institutional Specialist - West
lbroerman@quorumreview.com
T| 513-417-4234
The Institution Bulletin is a special publication of the
Quorum Forum, and brought to you by the Institution
Team at Quorum Review IRB.
5
6
Id. at 8.
Id. at 12.
7
8
9
Id. at 8-14.
Id. at 15-17.
Id. at 18.
5