Institutional BulletinLetter from the CEO

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-to-day 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, CEOQuorum Review IRB

1601 Fifth Avenue, Suite 1000 | Seattle, Washington 98101 T 206.448.4082 | F 206.448.4193 | QuorumReview.com

October 17, 2013 | Volume 3, Issue 4

Henrietta and David LacksCourtesy of the Lacks Family

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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Adequacy of Research Sites and the Determination of Whether an IND/IDE is Needed, is the finalized version of the Draft guidance of the same name, issued in 2012, and not much has changed from the original draft.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.

1 21 CFR 56.107(a).

2 21 CFR 56.111.

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)

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October 17, 2013 | Volume 3, Issue 4

Evaluating the Adequacy of the Research Site

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:

� 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.

Implications for Quorum Review IRB

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.

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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.

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Learn more about Quorum’s customized processes for the ethics review of institutional research at:

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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 (continued)4 Id. at 4-5

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October 17, 2013 | Volume 3, Issue 4

Bioavailability or Bioequivalence Studies

An IND is not required for bioavailability or bioequivalence studies if the following criteria are met:

� 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

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

5 Id. at 8.6 Id. at 12.

Additional Topics Covered

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

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.

7 Id. at 8-14.8 Id. at 15-17.9 Id. at 18.

Contact Quorum ReviewInterested 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.

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