SOCRA - IRBs

Exemptions from IRB requirement

1. An investigation which began before 7/27/81
2. Emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review.
3. Taste and food quality evaluations and consumer acceptance studies, if wholesome foods without additives are consumed or if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Who must register?

Each IRB in the United States that reviews clinical investigations regulated by FDA and each IRB in the United States that reviews clinical investigations that are intended to support applications for research or marketing permits for FDA-regulated products must register at a site maintained by the Department of Health and Human Services (HHS).

What information must an IRB register? (7)

(1) Institution operating the IRB (name, mailing address, and street address (if different))
(2) the senior officer of that institution who is responsible for overseeing activities performed by the IRB (the name, mailing address, phone number, facsimile number, and electronic mail address)
(3) the IRB's name, mailing address, street address (if different), phone number, facsimile number, and electronic mail address
(4) Each IRB chairperson's name, phone number, and electronic mail address
(5) the contact person providing the registration information (name, mailing address, phone number, facsimile number, and electronic mail address)
(6) The approximate # of active protocols involving FDA-regulated products reviewed
(7) Description of the types of FDA-regulated products (such as biological products, color additives, food additives, human drugs, or medical devices) involved in the protocols that the IRB reviews.

For purposes of this rule, an "active protocol" is...

any protocol for which an IRB conducted an initial review or a continuing review at a convened meeting or under an expedited review procedure during the preceding 12 months

When must an IRB register?

Each IRB must submit an initial registration. The initial registration must occur before the IRB begins to review a clinical investigation. Each IRB must renew its registration every 3 years. IRB registration becomes effective after review and acceptance by HHS.

Where can an IRB register?

Each IRB may register electronically through http://ohrp.cit.nih.gov/efile. If an IRB lacks the ability to register electronically, it must send its registration information, in writing, to the Office of Good Clinical Practice, Office of Special Medical Programs, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993.

Registration updated within 90 days of the change:

if an IRB's contact or chair person information changes the IRB must revise its registration information

Must be reported within 30 days of the change:

1. An IRB's decision to review new types of FDA-regulated products (such as a decision to review studies pertaining to food additives whereas the IRB previously reviewed studies pertaining to drug products), or to discontinue reviewing clinical investigations regulated by FDA
2. An IRB's decision to disband

All other information changes may be reported when

the IRB renews its registration (every 3 years).

How does an IRB revise its registration information?

The revised information must be sent to FDA either electronically or in writing in accordance with paragraph (d) of this section (electronically or to address in writing)

Requirements for IRB make-up (6)

1. A least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution.
2. At least 1 member w/ primary concerns in scientific areas
3. At least one member whose primary concerns are in nonscientific areas.
4. At least one member who is not otherwise affiliated with the institution and who is not part of the immediate family of a person who is affiliated with the institution.
5. No IRB may have a member participate in the IRB's initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.
6. An IRB may, in its discretion, invite individuals with competence in special areas to assist in the review of complex issues which require expertise beyond or in addition to that available on the IRB. These individuals may not vote with the IRB.

Considerations for make-up of IRB (5)

1. Experience, expertise, diversity (race, gender, culture), sensitivity to issues such as community attitudes, promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects
2. Both review specific research activities and ascertain the acceptability in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice.
3. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with those subjects.
4. Every nondiscriminatory effort will be made to ensure that no IRB consists entirely of men or entirely of women, including the institution's consideration of qualified persons of both sexes, so long as no selection is made to the IRB on the basis of gender.
5. No IRB may consist entirely of members of one profession.

In order to fulfill the requirements of these regulations, each IRB shall: (a) Follow written procedures: (4)

(1) For conducting its initial and continuing review of research and for reporting its findings and actions to the investigator and the institution;
(2) for determining which projects require review more often than annually and which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review;
(3) for ensuring prompt reporting to the IRB of changes in research activity; and
(4) for ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects.

(b) Follow written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the Food and Drug Administration of: (3)

(1) Any unanticipated problems involving risks to human subjects or others;
(2) any instance of serious or continuing noncompliance with these regulations or the requirements or determinations of the IRB; or
(3) any suspension or termination of IRB approval.

(c) Except when an expedited review procedure is used, review proposed research at...

convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas.

In order for the research to be approved ...

it shall receive the approval of a majority of those members present at the meeting.

The IRB has the authority to review and...

to approve, require modifications in (to secure approval), or disapprove all research activities covered by these regulations

IRB and ICF

shall require that information given to subjects as part of informed consent is in accordance with §50.25. The IRB may require that information, in addition to that specifically mentioned in §50.25, be given to the subjects when in the IRB's judgment the information would meaningfully add to the protection of the rights and welfare of subjects.

An IRB shall require documentation of informed consent in accordance with §50.27 of this chapter, except as follows (2)

(1) The IRB may, for some or all subjects, waive the requirement that the subject, or the subject's legally authorized representative, sign a written consent form if it finds that the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context (the IRB may require the investigator to provide subjects with a written statement regarding the research.); or
(2) The IRB may, for some or all subjects, find that the requirements in §50.24 of this chapter for an exception from informed consent for emergency research are met.

An IRB shall notify investigators and the institution in writing of its decision to approve or disapprove the proposed research activity, or of modifications required to secure IRB approval of the research activity. If the IRB decides to disapprove a research activity, it shall include in its written notification...

a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.

For investigations involving an exception to informed consent under §50.24 of this chapter, an IRB shall promptly notify in writing ...

the investigator and the sponsor of the research when an IRB determines that it cannot approve the research because it does not meet the criteria in the exception provided under §50.24(a) of this chapter or because of other relevant ethical concerns. The written notification shall include a statement of the reasons for the IRB's determination

IRB continuing review

at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and the research.

When some or all of the subjects in a study are children

an IRB must determine that the research study is in compliance with part 50, subpart D of this chapter, at the time of its initial review of the research

An IRB may use the expedited review procedure to review either or both of the following:

(1) Some or all of the research appearing on the list and found by the reviewer(s) to involve no more than minimal risk,
(2) minor changes in previously approved research during the period (of 1 year or less) for which approval is authorized.

Under an expedited review procedure, the review may be carried out by...

the IRB chairperson or by one or more experienced reviewers designated by the IRB chairperson from among the members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the nonexpedited review procedure set forth in §56.108(c).

list of categories of research that may be reviewed by the IRB through an expedited review procedure

published by the FDA in the FEDERAL REGISTER (republished as amended)

(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:

(1) Risks to subjects are minimized
(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.
(3) Selection of subjects is equitable.
(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with and to the extent required by part 50.
(5) Informed consent will be appropriately documented, in accordance with and to the extent required by §50.27.
(6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
(7) Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.

(1) Risks to subjects are minimized: (2)

(i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
(ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.

Weighing risks and benefits

The IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

Selection of subjects is equitable

In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons.

Vulnerable populations and undue influence

(b) When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards have been included in the study to protect the rights and welfare of these subjects.

Suspension or termination of IRB approval of research.

An IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB's action and shall be reported promptly to the investigator, appropriate institutional officials, and the Food and Drug Administration.

Cooperative research.

In complying with these regulations, institutions involved in multi-institutional studies may use joint review, reliance upon the review of another qualified IRB, or similar arrangements aimed at avoidance of duplication of effort.

An institution, or where appropriate an IRB, shall prepare and maintain adequate documentation of IRB activities, including the following:

(1) Copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents, progress reports submitted by investigators, and reports of injuries to subjects.
(2) Minutes of IRB meetings which shall be in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controverted issues and their resolution.
(3) Records of continuing review activities.
(4) Copies of all correspondence between the IRB and the investigators.
(5) A list of IRB members identified by name; earned degrees; representative capacity; indications of experience such as board certifications, licenses, etc., sufficient to describe each member's chief anticipated contributions to IRB deliberations; and any employment or other relationship between each member and the institution; for example: full-time employee, part-time employee, a member of governing panel or board, stockholder, paid or unpaid consultant.
(6) Written procedures for the IRB as required by §56.108 (a) and (b).
(7) Statements of significant new findings provided to subjects, as required by §50.25.

The records required by this regulation shall be retained

for at least 3 years after completion of the research, and the records shall be accessible for inspection and copying by authorized representatives of the Food and Drug Administration at reasonable times and in a reasonable manner

If apparent noncompliance with these regulations in the operation of an IRB is observed by an FDA investigator during an inspection,

the inspector will present an oral or written summary of observations to an appropriate representative of the IRB. The Food and Drug Administration may subsequently send a letter describing the noncompliance to the IRB and to the parent institution. The agency will require that the IRB or the parent institution respond to this letter within a time period specified by FDA and describe the corrective actions that will be taken by the IRB, the institution, or both to achieve compliance with these regulations.

On the basis of the IRB's or the institution's response, FDA may schedule a reinspection to confirm the adequacy of corrective actions. In addition, until the IRB or the parent institution takes appropriate corrective action, the Agency may require the IRB to:

(1) Withhold approval of new studies subject to the requirements of this part that are conducted at the institution or reviewed by the IRB;
(2) Direct that no new subjects be added to ongoing studies subject to this part; or
(3) Terminate ongoing studies subject to this part when doing so would not endanger the subjects.

When the apparent noncompliance creates a significant threat to the rights and welfare of human subjects...

FDA may notify relevant State and Federal regulatory agencies and other parties with a direct interest in the Agency's action of the deficiencies in the operation of the IRB.

Administrative actions for noncompliance are directed to...

The parent institution is presumed to be responsible for the operation of an IRB, and the FDA will ordinarily direct any administrative action under this subpart against the institution. However, depending on the evidence of responsibility for deficiencies, determined during the investigation, the FDA may restrict its administrative actions to the IRB or to a component of the parent institution determined to be responsible for formal designation of the IRB.

the Commissioner will institute proceedings in accordance with the requirements for a regulatory hearing set forth in part 16

whenever the IRB or the institution has failed to take adequate steps to correct the noncompliance stated in the letter sent by the agency under §56.120(a), and the Commissioner of Food and Drugs determines that this noncompliance may justify the disqualification of the IRB or of the parent institution

The Commissioner may disqualify an IRB or the parent institution if the Commissioner determines that:

(1) The IRB has refused or repeatedly failed to comply with any of the regulations set forth in this part, and

(2) The noncompliance adversely affects the rights or welfare of the human subjects in a clinical investigation.

If the Commissioner determines that disqualification is appropriate,

the Commissioner will issue an order that explains the basis for the determination and that prescribes any actions to be taken with regard to ongoing clinical research conducted under the review of the IRB. The FDA will send notice of the disqualification to the IRB and the parent institution. Other parties with a direct interest, such as sponsors and clinical investigators, may also be sent a notice of the disqualification. In addition, the agency may elect to publish a notice of its action in the FEDERAL REGISTER.

What happens to research and marketing permits if IRB is disqualified

The FDA will not approve an application for a research permit for a clinical investigation that is to be under the review of a disqualified IRB or that is to be conducted at a disqualified institution, and it may refuse to consider in support of a marketing permit the data from a clinical investigation that was reviewed by a disqualified IRB as conducted at a disqualified institution, unless the IRB or the parent institution is reinstated as provided in §56.123.

Reinstatement of an IRB or an institution.

An IRB or an institution may be reinstated if the Commissioner determines, upon an evaluation of a written submission from the IRB or institution that explains the corrective action that the institution or IRB plans to take, that the IRB or institution has provided adequate assurance that it will operate in compliance with the standards set forth in this part. Notification of reinstatement shall be provided to all persons notified under §56.121(c).

Actions alternative or additional to disqualification.

Disqualification of an IRB or of an institution is independent of, and neither in lieu of nor a precondition to, other proceedings or actions authorized by the act. The Food and Drug Administration may, at any time, through the Department of Justice institute any appropriate judicial proceedings (civil or criminal) and any other appropriate regulatory action, in addition to or in lieu of, and before, at the time of, or after, disqualification. The agency may also refer pertinent matters to another Federal, State, or local government agency for any action that that agency determines to be appropriate.