[Federal Register Volume 69, Number 128 (Tuesday, July 6, 2004)]
[Proposed Rules]
[Pages 40556-40562]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-15131]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 56
[Docket No. 2004N-0242]
Institutional Review Boards; Registration Requirements
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
require institutional review boards (IRBs) to register at a site
maintained by the Department of Health and Human Services (HHS). The
registration information would include contact information, the number
of active protocols involving FDA-regulated products reviewed in the
previous calendar year, and a description of the types of FDA-regulated
products involved in the protocols reviewed. The proposed IRB
registration requirements would make it easier for FDA to inspect IRBs
and to convey information to IRBs.
DATES: Submit written or electronic comments on this proposed rule by
October 4, 2004. Submit written comments on the information collection
provisions by August 5, 2004. See section III of this document for the
proposed effective date of any final rule based on this document.
ADDRESSES: You may submit comments, identified by Docket No. 2004N-
0242, by any of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
E-mail: [email protected]. Include Docket No. 2004N-
0242 in the subject line of your e-mail message.
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
Instructions: All submissions received must include the agency name
and Docket No. 2004N-0242 for this rulemaking. All comments received
will
[[Page 40557]]
be posted without change to http://www.fda.gov/dockets/ecomments,
including any personal information provided. For detailed instructions
on submitting comments and additional information on the rulemaking
process, see section IX of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.fda.gov/dockets/ecomments and/or
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. You may submit comments on the information
collection provisions to the Office of Management and Budget (OMB) by
the following method:
FAX: 202-395-6974. OMB is still experiencing significant
delay in the regular mail, including first class and express mail, and
messenger deliveries are not being accepted. To ensure that comments on
the information collection are received, OMB recommends that written
comments be faxed to the Office of Information and Regulatory Affairs,
OMB, Attn: Fumie Yokota, Desk Officer for FDA.
FOR FURTHER INFORMATION CONTACT: Philip L. Chao, Office of Policy and
Planning (HF-23), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-0587.
SUPPLEMENTARY INFORMATION:
I. Introduction
IRBs are boards, committees, or groups formally designated by an
institution to review, to approve the initiation of, and to conduct
periodic review of, biomedical research involving human subjects. (See
Sec. 56.102(g) (21 CFR 56.102(g)).) An IRB's primary purpose during
such reviews is to assure the protection of the rights and welfare of
human subjects (Sec. 56.102(g)). FDA's general regulations pertaining
to IRBs are in part 56 (21 CFR part 56). (While section 520(g) of the
Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360j(g))
refers to ``institutional review committees'' rather than IRBs, FDA
considers institutional review committees to be IRBs and to be subject
to the IRB regulations.)
Even though IRBs play an important role in the conduct of clinical
investigations regulated by FDA, FDA has never compiled a comprehensive
list of IRBs involved in reviewing clinical investigations regulated by
FDA. Existing FDA regulations have required some, but not all, clinical
investigators or sponsors of clinical investigations to provide IRB
names and addresses to FDA, and the requirements differ slightly. For
example, for human drug products, the sponsor must disclose the name
and address of ``each reviewing'' IRB. (See 21 CFR
312.23(a)(6)(iii)(b).) For medical devices, the sponsor must disclose
the names and addresses of IRBs that have ``been asked or will be
asked'' to review the investigation (see 21 CFR 812.20(b)(6)) (emphasis
added). For other types of clinical investigations regulated by FDA
(such as food additive studies involving human subjects), the
regulations do not expressly require the sponsor or the clinical
investigator to disclose or keep records showing an IRBs name and
address, and they make no distinction between ``reviewing IRBs'' and
IRBs that have been asked or will be asked to review a study.
In 1998, HHS's Office of Inspector General (OIG) issued several
reports on IRBs. OIG sought to identify the challenges facing IRBs and
to make recommendations on improving Federal oversight of IRBs. One
recommendation was that all IRBs should register with the Federal
Government on a regular basis as part of an effort to develop more
streamlined, coordinated, and probing means of assessing IRB
performance and to enhance the Federal Government's ability to identify
and respond to emerging problems before they result in ``serious
transgressions'' (Ref. 1, pp. 20 and 21).
After reviewing the OIG's recommendation, FDA has concluded that
IRB registration would serve several important goals. IRB registration
would:
Enable FDA to identify more precisely those IRBs reviewing
clinical investigations regulated by FDA. At present, much of FDA's
knowledge about the identities and numbers of IRBs reviewing clinical
investigations regulated by FDA is based on information from persons
conducting or sponsoring clinical investigations rather than from IRBs
themselves. This information may be obsolete (because there may be no
obligation to update the information) or incomplete (because the
requirements to report the names and addresses of IRBs are not uniform
across all FDA-regulated products);
Enable FDA to send educational information and other
information to IRBs. Because FDA lacks an accurate list of IRBs, FDA's
outreach and educational efforts are not as efficient as they might be.
Changes in IRB addresses result in returned mail, and newly-formed IRBs
may not appear on FDA's mailing lists; and
Help FDA identify IRBs for inspection, because the agency
would have a more accurate list of IRBs.
FDA, in conjunction with HHS' Office for Human Research Protection
(OHRP), is developing an Internet site for IRB registration purposes.
The goal is to create a simple, electronic registration system that all
IRBs, regardless of whether they review clinical investigations
regulated by FDA or research conducted or supported by HHS, can use.
(FDA discusses the Internet site in greater detail later in this
document.)
Elsewhere in this issue of the Federal Register, OHRP has published
a proposed rule to require IRB registration of IRBs that review
research that is conducted or supported by HHS and that are designated
under an assurance of compliance with HHS human subjects protection
regulations. FDA and OHRP proposed rules would create a single HHS IRB
registration system. Information regarding public disclosure of IRB
registration information, the Freedom of Information Act (FOIA), and
the Privacy Act of 1974 may be found in the OHRP proposed rule.
However, insofar as IRB registration information required by FDA's
proposed rule is concerned, the name of the institution operating the
IBR, as well as the IRB's name, will be publicly accessible. All other
IRB registration information that would be required by FDA under this
proposal would be subject to public disclosure under FOIA and FDA's
public information regulations at 21 CFR part 20.
II. Description of the Proposed Rule
The proposed rule would amend the IRB regulations at part 56 to
require IRB registration. The proposed rule would also delete an
obsolete cross-reference to a nonexistent FDA regulation.
A. IRB Registration (Proposed Sec. 56.106)
1. Who Must Register? (Proposed Sec. 56.106(a))
The proposal would create a new Sec. 56.106, entitled
``Registration'' to require IRBs to register at a site maintained by
HHS. In brief, proposed Sec. 56.106(a) would require registration of:
Each IRB in the United States that reviews clinical
investigations regulated by FDA under section 505(i) or 520(g) of the
act (21 U. S. C. 355(i)). A research permit under section 505(i) of the
act is usually known as an investigational new drug application (IND),
and a research permit under section 520(g) of the act is usually known
as an investigational device exemption (IDE); and
Each IRB in the United States that reviews clinical
investigations that support applications for research or marketing
permits for FDA-regulated products.
[[Page 40558]]
FDA requests comment on whether there are circumstances in which
foreign IRBs should be required or invited to register.
Proposed Sec. 56.106(a) would also specify that an individual
authorized to act on the IRB's behalf must submit the registration
information. The individual may be an IRB member or any other person
authorized by the IRB to submit the registration information.
FDA considered requiring sponsors or clinical investigators to
submit IRB registration, but rejected such an approach because it
created the potential for multiple IRB registrations for the same IRB.
For example, if two sponsors used a particular IRB and the proposed
rule would require sponsors to submit IRB registration information, the
result would be two registrations for the same IRB. Thus, it would be
more practical and efficient to require the IRBs themselves to
register.
2. What Information Must an IRB Provide When Registering? (Proposed
Sec. 56.106(b))
Proposed Sec. 56.106(b) would describe the information to be
submitted as part of the registration process. In brief, the proposal
would require IRBs to provide:
The name and mailing address of the institution operating
the IRB and the name, mailing address, phone number, fax number, and e-
mail address of the senior officer of that institution who is
responsible for overseeing activities performed by the IRB. The senior
officer must not be an IRB member, IRB staff, or a sponsor or
investigator participating in an investigation under review by that
IRB. This information would enable FDA to identify the institution with
which the IRB is affiliated. Information on the institution would also
enable FDA to determine, if there are problems with an IRB, whether
similar problems exist at other IRBs affiliated with that institution.
Information on the senior officer of the institution would enable FDA
to contact that person directly if significant issues or problems arose
that involved or could involve the institution;
The IRB's name, the IRB chairperson's name, the name of
the contact person for the IRB (if different from the IRB chairperson),
and the mailing addresses and street addresses (if different from the
mailing address), phone numbers, fax numbers, and e-mail addresses for
the IRB chairperson and contact person (if different from the IRB
chairperson). This information would enable FDA to contact an IRB
contact person on routine issues and to contact an IRB chairperson
quickly, if necessary, on important issues and to send electronic mail
to the IRB chairperson and contact person;
The number of active protocols involving FDA-regulated
products reviewed (both initial reviews and continuing reviews). In
this case, ``active protocol'' would mean any protocol for which an IRB
conducted an initial review or a continuing review during the preceding
calendar year. The proposal would not require an IRB to report a
specific number of protocols; instead, IRBs would indicate the range of
the numbers of protocols they had reviewed in the preceding calendar
year. The proposal would consider a ``small'' number of protocols to be
1 to 25 protocols; ``medium'' would be 26 to 499, and ``large'' would
be 500 protocols or more. This information would enable FDA to
determine how active an IRB is and to assign its inspection resources
based on an IRB's activity level;
A description of the types of FDA-regulated products, such
as human drugs, biological products (which include, but are not limited
to, vaccines, blood, blood products, and tissues), medical devices,
food additives, and/or color additives involved in the protocols that
the IRB reviews. This information would allow FDA to send appropriate
information (such as information pertaining to the product or a class
of products, new regulatory requirements, or new guidance documents) to
the IRB and to assign appropriate personnel to conduct IRB inspections;
and
An indication as to whether the IRB is accredited and, if
it is accredited, the date of its last accreditation and the name of
the accrediting body or organization. FDA recognizes that IRB
accreditation is a developing concept, so information on IRB
accreditation will help FDA evaluate the extent and value of IRB
accreditation and help identify the accrediting bodies or
organizations. FDA specifically solicits public comment related to the
perceived value of collecting information on the accreditation status
of IRBs.
Due to statutory and regulatory differences between FDA and OHRP,
the Internet registration site may request more information from IRBs
reviewing research conducted or supported by HHS than those reviewing
clinical investigations regulated by FDA that are not conducted or
supported by HHS. For example, OHRP may request information concerning
the IRB chairperson's status (e.g., physician-scientist, other
scientist, or nonscientist) and educational degrees and also ask for a
list of IRB members and alternates. In those instances where the
Internet registration site would seek more information than FDA would
require under this proposal, the site would clarify that IRBs regulated
solely by FDA may, but are not required to, provide the additional
information.
3. When Must an IRB Register? (Proposed Sec. 56.106(c))
Proposed Sec. 56.106(c) would require IRBs to register once and to
renew their registrations every 3 years. The proposal would require
initial IRB registration within 30 days before the date when the IRB
intends to review clinical investigations regulated by FDA. To show how
this would work, assume that a newly formed IRB has been asked to
review a protocol for a clinical investigation regulated by FDA under
section 505(i) of the act. The IRB would then be subject to FDA's IRB
regulations (Sec. 56.101(a)), and the IRB, under proposed Sec.
56.106(c), would submit its initial registration 30 days before the
date the IRB intends to review the protocol. (If the IRB declined to
review the protocol, the IRB would not necessarily be subject to FDA
regulation and would not have to register under this proposal.)
Requiring IRBs to renew their registrations periodically would help
ensure that FDA's list of IRBs remains current. (See section III of
this document regarding the rule's implementation for IRBs already
reviewing clinical investigations when FDA issues a final rule.)
Under the proposal, IRB registration would become effective when
HHS posts that information on its Web site. FDA also recognizes that
some IRBs may have voluntarily registered under the OHRP system, and
OHRP will continue to recognize such registrations.
4. Where Can an IRB Register? (Proposed Sec. 56.106(d))
Proposed Sec. 56.106(d) would direct IRBs to register at a
specific Internet address (which FDA will provide when it issues any
final rule) or, if an IRB lacks the ability to register electronically,
to send its registration information to a specific mail address (which
FDA will provide in a final rule). Although electronic registration may
be easier and faster than written registration, FDA cannot determine
how widespread Internet access is among IRBs. Thus, the agency will
allow for written registration as an alternative to electronic
registration, but invites comment on whether it should discontinue
written IRB registration procedures after some time period has elapsed.
[[Page 40559]]
5. How Does an IRB Revise Its Registration Information? (Proposed Sec.
56.106(e))
Under proposed Sec. 56.106(e), if an IRB's contact registration
information changes, the IRB must revise its registration information
within 90 days of the change. All information involving changes other
than changes in an IRB contact or an IRB chairperson only need to be
updated at the time of the 3- year renewal under proposed Sec.
56.106(c). For example, if an IRB selects a new chairperson, the IRB
would, under proposed Sec. 56.106(e), revise its registration
information within 90 days of the new chairperson's selection. If an
IRB reviews new types of FDA-regulated products, the IRB, under
proposed Sec. 56.106(e), would revise its registration information to
reflect this change within 30 days.
Proposed Sec. 56.106(e) would also consider an IRB's decision to
disband or stop reviewing clinical investigations regulated by FDA to
be a change that must be reported. Requiring IRBs to report when they
have disbanded or stopped reviewing clinical investigations regulated
by FDA will enable FDA to stop sending educational information to the
IRB and also forego inspecting the IRB.
Revised registration information would be submitted electronically
at the Internet address (which FDA will identify by the time it issues
a final rule). If an IRB lacks Internet access, it would submit any
revised registration information, in writing, to a specific mail
address (which FDA will identify by the time it issues a final rule).
6. What Happens if an IRB Does Not Register?
As stated earlier, requiring IRBs to register will help FDA send
educational information to IRBs and identify IRBs for inspection. If
sponsors of clinical investigations or marketing applications and
investigators could use unregistered IRBs, those IRBs would not have
had the benefit of receiving educational materials from FDA and would
not have been identified on an FDA IRB registration list for future
inspection. Therefore, to the extent that any existing FDA regulation
requires a sponsor or investigator to comply with part 56 or to use an
IRB that complies with part 56, FDA will consider sponsors and
investigators using an unregistered IRB to be in conflict with their
regulatory obligations. For example, the IND regulations in Sec.
312.66 (21 CFR Sec. 312.66), require an investigator to use an IRB
that complies with part 56. If the investigator uses an unregistered
IRB, FDA would consider the sponsor or investigator to be in violation
of its obligations under Sec. 312.66. (See also Sec.
312.53(c)(1)(vii) (IND sponsor must obtain a commitment by the
investigator that an IRB that complies with part 56 will be responsible
for the initial and continuing review and approval of the clinical
investigation); 21 CFR 361.1(d)(5) (investigators studying radioactive
drugs must obtain review and approval by an IRB that complies with part
56); Sec. 812.42 (21 CFR 812.42) (sponsor shall not begin a device
investigation until an IRB and FDA have approved the application or
supplemental application relating to the investigation); Sec. 812.60
(IRB reviewing and approving device investigations must comply with
part 56 in all respects)). An IRB that refuses to register may be
subject to administrative action for noncompliance (see, e.g.,
Sec. Sec. 56.120, 56.121, and 56.124). FDA believes that the proposed
registration requirement is both simple and straightforward and
beneficial to IRBs, so the agency does not expect that many IRBs will
refuse or fail to register.
FDA considered other options to require sponsors and investigators
to use only registered IRBs. For example, one option would be to refuse
to consider information from an application for a research permit for a
clinical investigation that is reviewed or is to be reviewed by an
unregistered IRB. This would have given sponsors and investigators a
strong incentive to use only registered IRBs and would have been
similar to Sec. 56.121(d) (which describes FDA's actions if a clinical
investigation is reviewed by a disqualified IRB). However, the agency
did not consider an IRB's failure to reregister to be comparable to an
IRB's status as disqualified, so FDA did not include such a provision
in the proposed rule. FDA invites comments on how it could best ensure
that all sponsors and investigators involved in clinical investigations
using human subjects use only registered IRBs to review and approve
those clinical investigations. The agency is particularly interested in
the following issues:
What sanctions or administrative mechanisms, if any,
should be or might be used against sponsors and investigators who use
unregistered IRBs? For example, should FDA amend the IND regulations to
authorize the agency to place a study on clinical hold if a sponsor or
investigator uses an unregistered IRB?
Are additional changes to FDA regulations necessary? For
example, would FDA have to revise or create requirements for sponsors
and investigators? If so, which provisions would FDA have to revise?
What new regulations would be needed?
Are there other ways to ensure the use of registered IRBs?
B. Nonsubstantive, Technical Amendment to Part 56
The proposal would also make a nonsubstantive amendment to part 56.
The proposal would revise the definition of ``An Application for an
Investigational Device Exemption'' at Sec. 56.102(b)(12) to eliminate
the reference to part 813 (21 CFR part 813). This change is necessary
because FDA removed the regulations at part 813 (which pertained to
intraocular lenses) in 1997 (see 62 FR 4164, January 29, 1997).
III. Implementation
FDA intends to make any final rule based on this proposal effective
within 60 days after the final rule is published in the Federal
Register. Because the registration requirement would be new, the agency
would then give all IRBs an additional 60 days to submit their initial
registrations. For example, if FDA published the final rule in the
Federal Register on January 1, 2005, the final rule would become
effective on March 1, 2005 (60 days after the final rule's publication
date), and IRBs would have another 60 days, to April 30, 2005, to
submit their initial registration information. After this initial
deadline, all subsequent registrations would adhere to the timeframes
in proposed Sec. 56.106(c).
FDA invites comment as to whether this tentative implementation
schedule should be revised. Because IRB registration will eventually
occur primarily through the Internet, the actual effective date of any
final rule may change should any software or hardware problems arise
that affect FDA's ability to obtain IRB registration information
electronically.
IV. Legal Authority
In general, the act authorizes FDA to issue regulations pertaining
to investigational uses of FDA-regulated products (see, e.g., section
409(j) of the act (21 U. S. C. 348(j)) (investigations involving food
additives); section 505(i) of the act (investigations involving human
drugs); section 520(g) of the act (investigations involving devices);
and 721(f) of the act (21 U.S.C. 379e(f)) (investigations involving
color additives)). Two provisions specifically refer to the use of IRBs
as part of the investigational process (see sections 505(i) and 520(g)
of the act (section
[[Page 40560]]
520(g) of the act refers to ``institutional review committees'' rather
than IRBs, but the terms are synonymous)).
The act also requires the submission of a petition or application
to FDA (see, e.g., sections 409(b) of the act (food additive
petitions); section 505(b) of the act (new drug applications); section
505(j) of the act (abbreviated new drug applications); section 515(c)
of the act (21 U.S.C. 360e(c)) (premarket approval applications for
devices); and section 721(b) of the act (color additive petitions))
before marketing begins.
To implement these provisions of the act, section 701(a) of the act
(21 U.S.C. 371(a)) gives FDA the authority to issue regulations for the
efficient enforcement of the act. By requiring IRB registration, the
proposed rule would, if finalized, aid in the efficient enforcement of
the act's provisions regarding the investigational use of various FDA-
regulated products (because then FDA would be able to conduct IRB
inspections more efficiently). IRB registration would also help enforce
those provisions regarding marketing applications (because marketing
applications usually depend on clinical investigations involving human
subjects, and IRBs are supposed to provide protections for the rights
and welfare of such human subjects). Moreover, by requiring IRBs to
register, the proposed rule would enable FDA to contact IRBs more
quickly and efficiently on various issues, such as adverse reactions
that may be attributed to a particular product, new regulatory
requirements or policies, or problems associated with a particular
protocol or clinical investigator. FDA's authority to regulate IRBs was
discussed in more detail in the preambles to the initial proposed rule
and the final rule establishing part 56 (43 FR 35186 at 35197, August
8, 1978 and 46 FR 8958 at 8959 and 8960, January 27, 1981). For the
reasons discussed in the earlier preambles and previously on this
document FDA concludes that it has sufficient legal authority to issue
the proposed rule.
V. Economic Impact Analysis
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Under the Regulatory
Flexibility Act, if a rule has a significant impact on a substantial
number of small entities, an agency must analyze regulatory options
that would minimize any significant impact of the rule on small
entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in an expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 (adjusted annually for inflation) in
any one year.''
The proposed rule is consistent with the principles set forth in
Executive Order 12866 and these two statutes. As explained below, the
proposed rule is not an economically significant regulatory action as
defined in Executive Order 12866 and does not require a Regulatory
Flexibility Analysis. The Unfunded Mandates Reform Act does not require
FDA to prepare a statement of costs and benefits for the proposed rule
because the proposed rule is not expected to result in any 1-year
expenditure that would exceed $100 million adjusted for inflation. The
current inflation-adjusted statutory threshold is approximately $110
million.
The proposed rule would require IRBs to register with FDA. The
information sought through the registration process would be minimal,
consisting largely of names and addresses for a contact person, the
institution operating the IRB (if an institution exists), the senior
officer of the institution who is responsible for overseeing the
activities performed by the IRB, the IRB, and the IRB chairperson. The
registration would also indicate whether the IRB reviews a ``small,''
``medium,'' or ``large'' number of FDA-regulated protocols and the
types of FDA-regulated products involved. IRBs would also indicate
whether they are accredited and identify the accrediting body or
organization. FDA estimates that initial IRB registration may require 1
hour to complete. If the average wage rate is $40 per hour, this means
that each IRB would spend $40 for an initial registration ($40 per hour
x 1 hour per initial registration).
FDA estimates that reregistration would require less time,
especially if the IRB verifies existing information. If reregistration
requires 30 minutes, then the cost of reregistration to each IRB would
be approximately $20 ($40 per hour x 0.5 hours per reregistration).
Revising an IRB's registration information would probably involve
costs similar to reregistration costs. If the revision requires 30
minutes, then the cost of revising an IRB's registration information
would be approximately $20 per IRB.
Given the minimal registration information that would be required
and the low costs associated with registration, this proposed rule is
not a significant regulatory action, and FDA certifies that the
proposed rule would not have a significant economic impact on a
substantial number of small entities. Therefore, the proposal is not a
significant regulatory action under Executive Order 12866 and does not
require a Regulatory Flexibility Act analysis.
Additionally, assuming that an estimated 5,000 IRBs would register,
the proposed rule, if finalized, would result in a 1-year expenditure
of $200,000 (5,000 IRBs x $40 registration wage costs per IRB). Because
the total expenditure under the rule will not result in a 1-year
expenditure of $100 million or more, FDA is not required to perform a
cost-benefit analysis under the Unfunded Mandates Reform Act.
VI. Environmental Impact
FDA has determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VII. Paperwork Reduction Act of 1995
This proposed rule contains information collection requirements
that are subject to review by OMB under the Paperwork Reduction Act of
1995 (the PRA) (44 U.S.C. 3501-3520). The title, description, and
respondent description of the information collection provisions are
shown below with an estimate of the annual reporting and recordkeeping
burden. Included in the estimate is the time for reviewing
instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
FDA invites comments on these topics: (1) Whether the collection of
information is necessary for the proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the
[[Page 40561]]
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Institutional Review Boards: Registration Requirements.
Description: The proposed rule would require IRBs to register with
FDA.
Description of Respondents: Businesses and individuals.
The estimated burden associated with the information collection
requirements of this proposed rule is 8,750 hours.
Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
Annual Frequency per Total Annual
21 CFR Section No. of Respondents Response Responses Hours per Response Total Hours
----------------------------------------------------------------------------------------------------------------
56.106(c) 5,000 1 5,000 1 5,000
(initial
registration)
56.106(c) 2,500 1 2,500 0.5 1,250
(reregistratio
n)
56.106(e) 5,000 1 5,000 0.5 2,500
Total .................... .................... ............... .................. 8,750
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
FDA's estimates are based on the following considerations.
According to a 1998 OIG report, there are 3,000 to 5,000 IRBs in the
United States, and most are associated with hospitals and academic
centers (Ref. 1, p. 3). While not all IRBs are involved in clinical
investigations regulated by FDA, the agency, for purposes of the PRA,
will use 5,000 as the maximum number of IRBs subject to the proposed
rule. Additionally, because the proposed rule would require basic
information about an IRB (such as names and addresses) and because
registration would, in most cases, be done electronically, FDA will
assume that registration will take only 1 hour per IRB. Thus, the total
burden hours would be 5,000 hours (5,000 IRBs x 1 hour per IRB).
Reregistration and revisions to existing registration information
should require less time than initial registration. FDA will assume
that reregistration and revisions will take only 30 minutes per IRB.
FDA will also assume, based on OHRP's experience with its IRB
registration program, that 50 percent of IRBs (2,500) will reregister
and that all (5,000) will revise their registration information.
Therefore, the total burden hours for reregistration will be 1,250
hours (2,500 IRBs x 0.5 hours per IRB), and the total burden hours for
revisions will be 2,500 hours (5,000 IRBs x 0.5 hours per IRB).
In compliance with the PRA (44 U.S.C. 3507(d)), the agency has
submitted the information collection requirements of this rule to OMB
for review. Interested persons are requested to send comments regarding
information collection by August 5, 2004, to the Office of Information
and Regulatory Affairs, OMB. Submit written comments on the information
collection provisions by August 5, 2004. See section III of this
document for the effective date of any final rule based on this
document.
VIII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the rule does not contain policies that have substantial direct effects
on the States, on the relationship between the National Government and
the States, or on the distribution of power and responsibilities among
the various levels of government. Accordingly, the agency has concluded
that the rule does not contain policies that have federalism
implications as defined in the order and, consequently, a federalism
summary impact statement is not required.
IX. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this proposal.
Submit written comments to OMB (see the ADDRESSES in section VII of
this document) on the information collection provisions. Two paper
copies of any comments are to be submitted, except that individuals may
submit one paper copy. Comments are to be identified with the docket
number found in brackets in the heading of this document. Received
comments may be seen in the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
X. Reference
The following reference has been placed on display in the Division
of Dockets Management (see ADDRESSES) and may be seen by interested
persons between 9 a.m. and 4 p.m., Monday through Friday.
1. OIG, HHS, ``Institutional Review Boards: A Time for Reform,''
June 1998.
List of Subjects in 21 CFR Part 56
Human research subjects, Reporting and recordkeeping requirements,
Safety.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 56 be amended as follows:
PART 56--INSTITUTIONAL REVIEW BOARDS
1. The authority citation for 21 CFR part 56 continues to read as
follows:
Authority: 21 U.S.C. 321, 343, 346, 346a, 348, 350a, 350b, 351,
352, 353, 355, 360, 360c-360f, 360h-360j, 371, 379e, 381; 42 U.S.C.
216, 241, 262, 263b-263n.
Sec. 56.102 [Amended]
2. Section 56.102 is amended in paragraph (b)(12) by removing the
phrase ``parts 812 and 813'' and by adding in its place the phrase
``part 812.''
3. Section 56.106 is added to subpart A to read as follows:
Sec. 56.106 Registration.
(a) Who must register? Each IRB in the United States that reviews
clinical investigations regulated by FDA under section 505(i) or 520(g)
of the act 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). (A
research permit under section 505(i) of the act is usually known as an
investigational new drug application (IND), while a research permit
under section 520(g) of the act is usually known as an investigational
device exemption (IDE).) An individual authorized to act on the IRB's
behalf must submit the registration information.
[[Page 40562]]
(b) What information must an IRB register? Each IRB must provide
the following information:
(1) The name and mailing address of the institution operating the
IRB and the name, mailing address, phone number, facsimile number, and
electronic mail address of the senior officer of that institution who
is responsible for overseeing activities performed by the IRB;
(2) The IRB's name, the names of each IRB chair person and each
contact person (if one exists) for the IRB, and the IRB's mailing
address, street address (if different from the mailing address), phone
number, facsimile number, and electronic mail address;
(3) The number of active protocols (small, medium, or large)
involving FDA-regulated products reviewed (both initial reviews and
continuing reviews). For purposes of this regulation, an ``active
protocol'' is any protocol for which an IRB conducted an initial or
continuing review during the preceding calendar year. A ``small''
number of protocols is 1 to 25 protocols; ``medium'' is 26 to 499
protocols, and ``large'' is 500 protocols or more;
(4) A 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; and
(5) An indication whether the IRB is accredited and, if so, the
date of the last accreditation and the name of the accrediting body or
organization.
(c) When must an IRB register? Each IRB must submit an initial
registration within 30 days before the date when the IRB intends to
review clinical investigations regulated by FDA. Each IRB must renew
its registration every 3 years. IRB registration becomes effective when
HHS posts that information on its Web site.
(d) Where can an IRB register? Each IRB may register electronically
through [Web site address to be added in the final rule]. If an IRB
lacks the ability to register electronically, it must send its
registration information, in writing, to [mailing address to be added
in the final rule].
(e) How does an IRB revise its registration information? If an
IRB's contact or chair person information changes, the IRB must revise
its registration information by submitting any changes in that
information within 90 days of the change. An IRB's decision to disband
or to discontinue reviewing clinical investigations regulated by FDA is
a change that must be reported within 30 days of the change. All other
information changes may be reported when the IRB renews its
registration. The revised information must be sent either
electronically or in writing in accordance with paragraph (d) of this
section.
Dated: June 23, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-15131 Filed 7-2-04; 8:45 am]
BILLING CODE 4160-01-S