[Federal Register: January 15, 2009 (Volume 74, Number 10)]
[Rules and Regulations]
[Page 2358-2369]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15ja09-10]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 56
[Docket No. FDA-2004-N-0117] (formerly Docket No. 2004N-0242)
RIN 0910-AB88
Institutional Review Boards; Registration Requirements
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA, we) is issuing a final
rule to require institutional review boards (IRBs) to register through
a system maintained by the Department of Health and Human Services
(HHS). The registration information includes contact information (such
as addresses and telephone numbers), the number of active protocols
involving FDA-regulated products reviewed during the preceding 12
months, and a description of the types of FDA-regulated products
involved in the protocols reviewed. The IRB registration requirements
will make it easier for FDA to inspect IRBs and to convey information
to IRBs.
DATES: This rule is effective July 14, 2009. This effective date is
necessary to allow refinement of the electronic
[[Page 2359]]
registration system so that it corresponds to this final rule. All IRBs
must comply with the initial registration requirement and, if
necessary, make required revisions to their registrations by September
14, 2009.
FOR FURTHER INFORMATION CONTACT: Erik Mettler, Office of Policy,
Planning and Preparedness, Food and Drug Administration, WO1, rm. 4324,
Silver Spring, MD 20993-0002, 301-796-4830.
SUPPLEMENTARY INFORMATION:
I. Introduction
What Led Us to Issue This Rule?
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
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
(id.). FDA's general regulations pertaining to IRBs are at 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, we have 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 among
the different types of products regulated by FDA. 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)(7)) (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 IRB's 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, the Department of Health and Human Services' Office of the
Inspector General (OIG) issued several reports on IRBs. The 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'' (see Office of the
Inspector General, Department of Health and Human Services,
Institutional Review Boards: a Time for Reform, pages 20 and 21, June
1998).
After reviewing the OIG's recommendation, we concluded that IRB
registration would serve several important goals. IRB registration
would:
Enable us to identify more precisely those IRBs reviewing
clinical investigations regulated by FDA. At present, much of our
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 us to send educational information and other
information to IRBs. Because we lack an accurate list of IRBs, our
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 in FDA's mailing lists; and
Help us identify IRBs for inspection, because we would
have a more accurate list of IRBs.
Consequently, FDA, in consultation with the Department of Health
and Human Services, Office for Human Research Protections (OHRP),
published a proposed rule in the Federal Register of July 6, 2004 (69
FR 40556), that would require IRB registration for IRBs reviewing
clinical investigations involving FDA-regulated products. OHRP issued a
companion proposed rule which appeared in the Federal Register of July
6, 2004 (69 FR 40584) that would require registration for IRBs
reviewing federally supported research. The final OHRP IRB registration
rule is published elsewhere in this issue of the Federal Register.
The goal of the two rules is to create a simple, electronic
registration system that all IRBs, regardless of whether they review
clinical investigations regulated by FDA or federally supported
research, can use.
II. What Comments Did We Receive?
A. How Many Comments Did We Receive, and Who Submitted Comments?
We received over 15 comments in response to the proposed rule.
Individuals, IRB members, IRB associations, an IRB accreditation
association, government, health, academic or trade associations, a
university system, and drug companies submitted comments. In general,
the comments supported IRB registration, although some disagreed with
specific aspects of the proposal or with other issues that were
discussed in the preamble to the proposed rule. To make it easier to
identify comments and our responses, the word ``Comment,'' in
parentheses, will appear before the comment's description, and the word
``Response,'' in parentheses, will appear before our response. We have
also numbered each comment to help distinguish between different
comments. The number assigned to each comment is purely for
organizational purposes and does not signify the comment's value or
importance or the order in which it was received.
B. Who Must Register? (Section 56.106(a))
Proposed Sec. 56.106(a) would require the following IRBs to
register:
Each IRB in the United States that reviews clinical
investigations regulated by FDA under sections 505(i) (21 U.S.C.
355(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.
The preamble to the proposed rule invited comment on whether there
are circumstances in which foreign IRBs should be required or invited
to register (see 69 FR 40556 at 40558).
(Comment 1) One comment stated that foreign IRBs are not needed in
America.
(Response) The comment may have misinterpreted the preamble. The
issue is not whether foreign IRBs should or should not review studies,
but rather whether foreign IRBs should be included in the IRB
registration system.
(Comment 2) Several comments differed as to whether foreign IRBs
should have to register. One comment would require foreign IRBs to
register if they review research conducted in the
[[Page 2360]]
United States; the same comment would give foreign IRBs the option to
register if they review research conducted outside the United States
that may be used to support a future marketing application in the
United States.
Several comments would allow for voluntary registration of foreign
IRBs or ethical review committees. Two comments explained that
registering foreign IRBs would enable them to have access to
educational materials and other information. However, one comment would
limit such registration to foreign IRBs reviewing research conducted in
the United States, and another comment noted that local privacy laws in
foreign countries might affect a foreign IRB's ability to provide
certain registration information.
In contrast, one comment said that we should respect oversight of
ethical review committees by foreign authorities and that we should not
impose ``additional bureaucracy.'' Similarly, another comment opposed
registering foreign IRBs, stating that such registration could pose
``significant difficulties'' for clinical investigators and sponsors
and that foreign laws and regulations might make it difficult for
foreign IRBs to register.
(Response) We agree in part with the comments. We agree that
foreign IRBs would benefit from educational and other materials that
would be sent to registered IRBs. Therefore, we have revised Sec.
56.106(a) to allow for voluntary registration by foreign IRBs and by
any domestic IRB that is not otherwise required to register.
We decline to require registration by foreign IRBs that review
research to be conducted in the United States. We do not believe a
significant number of foreign IRBs review research that is to be
conducted in the United States. Furthermore, requiring registration by
foreign IRBs that review research conducted in the United States could
lead to arguments over the validity of our regulatory authority when
applied to actions occurring in a foreign country.
As for possible problems foreign IRBs might encounter in
registering information due to foreign laws and regulations, the
comments did not identify specific registration elements that would be
a problem. Consequently, we lack sufficient information to determine
whether we should modify certain IRB registration elements to
accommodate foreign IRBs.
(Comment 3) One comment asked us to clarify whether the reference
to section 520(g) of the act was limited to research done under an
investigational device exemption (IDE) or encompassed all
investigational devices in a clinical investigation.
(Response) The reference to section 520(g) of the act encompasses
all investigational devices in a clinical investigation, regardless of
whether FDA approval of an IDE is needed in accordance with 21 CFR part
812 for the clinical investigation.
(Comment 4) One comment asked us to clarify whether the rule
applied to ``non-local'' or ``commercial'' IRBs.
(Response) The comment did not explain what it meant by the terms
``non-local'' or ``commercial'' IRB. For purposes of this response, we
will assume that a ``non-local'' IRB is one that is physically located
away from the clinical trial site(s) and that a ``commercial'' IRB is
one that is paid to review research.
If the ``non-local'' or ``commercial'' IRB is located in the United
States and:
Reviews clinical investigations regulated by FDA under
sections 505(i) or 520(g) of the act; or
Reviews clinical investigations that are intended to
support applications for research or marketing permits for FDA-
regulated products, then the non-local or commercial IRB must register
under Sec. 56.106(a). If the non-local or commercial IRB does not
perform any of the reviews described immediately above or is outside
the United States, then it may register voluntarily.
C. What Information Must an IRB Register? (Section 56.106(b))
Proposed Sec. 56.106(b) would describe the information that IRBs
would provide as part of the registration process. For example,
proposed Sec. 56.106(b)(1) would require 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
the IRB's activities. (A facsimile number also is known more commonly
as a ``fax number.'')
(Comment 5) Several comments addressed the registration information
in proposed Sec. 56.106(b) generally. Two comments said that the
registration information that OHRP and FDA would require should either
be the same or that information required by OHRP, but not by FDA,
should be clearly delineated and marked as optional for IRBs that are
subject to FDA regulation. Similarly, one comment said that questions
relating to research funded by HHS, which were part of OHRP's proposed
registration system, should be identified clearly so IRBs that do not
review HHS-funded research are not obliged to answer those questions.
Another comment said the proposed registration information is
appropriate.
One comment urged us to reexamine the registration information to
assure that the information is necessary to support the rule's stated
goals.
(Response) We coordinated our rule with OHRP and tailored our
respective registration information elements to be as consistent as
possible and to use the same internet-based registration system.
We agree that the IRB registration system should specify whether
certain registration information is optional or not required for IRBs
subject only to our jurisdiction. The preamble to the proposed rule
stated that, ``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'' (69 FR 40556 at
40558). The Internet registration site will be structured so that
required information will be identified or marked as such, and IRBs
indicating that they are registering pursuant to FDA's regulation also
will be directed to questions requesting information required only
under FDA's regulation.
(Comment 6) Proposed Sec. 56.106(b)(1) would require IRBs to
provide 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.'' The
preamble to the proposed rule explained that 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'' (see 69 FR
40556 at 40558).
Several comments addressed this provision. Two comments supported
the proposed requirement, but two other comments stated that our
interpretation of ``senior officer'' was too prohibitive or too
restrictive. These comments said that if a senior officer is on the
IRB, his or her membership should not invalidate registration or
subject the IRB to enforcement action.
Another comment questioned what we meant when we referred to ``IRB
staff.'' The comment said that some IRBs distinguish staff from IRB
members to ensure the IRB's integrity and independence. The comment
suggested that we list persons who cannot be a ``senior officer'' and
that we delete ``IRB staff'' from that list.
(Response) We agree, in part, with the comments. We recognize that,
in some cases, it may not be feasible to identify
[[Page 2361]]
a ``senior officer'' who is not also an IRB member or IRB staff.
However, our experience indicates that IRBs sometimes form
subcommittees or other groups and that the institutions overseeing the
IRBs may not be aware of these subcommittees or other groups. Thus,
when we said that the ``senior officer'' should not be an IRB member or
IRB staffer, our goal was to ensure that the institution overseeing the
IRB's activities is truly aware of those activities. For these reasons,
where feasible, we recommend that the senior officer not be an IRB
member or an IRB staffer.
Additionally, as the preamble to the proposed rule stated,
information regarding the institution will enable us to identify the
institution and to determine whether problems that might exist for one
IRB at that institution exist at other IRBs affiliated with that
institution (see 69 FR 40556 at 40558).
Additionally, on our own initiative, we have revised Sec.
56.106(b)(1) to require the street address for the institution if the
street address is different from the institution's mailing address.
(Comment 7) One comment said we should ensure that any addresses
and telephone numbers are current and are kept current. The comment
suggested that we issue fines and penalties if IRBs fail to keep such
information current.
(Response) Section 56.106(e) requires IRBs to revise their
registration information within 90 days if a contact person or
chairperson information changes; this would encompass changes in the
contact person's or chairperson's telephone number.
As for the comment's suggestion of imposing fines and penalties, we
do not have legal authority to impose fines for failure to maintain IRB
registration information. As for other penalties, we discuss the
consequences of failing to register in comment 24 of this document.
(Comment 8) Proposed Sec. 56.106(b)(2) would require IRBs to
provide 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.
One comment supported the proposal. However, another comment noted
that the OHRP proposal would require IRBs to provide the name, gender,
degree, scientific or nonscientific specialty, and affiliation of each
IRB member and suggested that we revise our rule to require the same
information as the OHRP rule.
(Response) We agree, in part, and disagree, in part, with the
comment's suggestion that we require the same information as OHRP's
rule. We decline to revise the rule as requested by the comment. Unlike
OHRP, we have never required IRBs to give us the names, educational
background, and qualifications of all IRB members. Our rule does not
include this information because our regulatory emphasis has been on
the IRB's overall composition. Consequently, our final rule does not
require such information about individual IRB members.
We have, however, revised Sec. 56.106(b)(2) to replace ``chair
person'' with ``chairperson.'' This change reflects the common spelling
for this noun and does not alter the application or interpretation of
Sec. 56.106(b)(2). Additionally, we have revised Sec. 56.106(b)(2) to
require the phone number and electronic mail address for the IRB
chairperson; this will enable us to communicate with the IRB
chairperson quickly if such a need arises.
On our own initiative, we have revised Sec. 56.106(b)(2) to delete
the parenthetical of ``(if one exists)'' after ``the contact person's
name'' and to require and the name, mailing address, phone number,
facsimile number, and electronic mail address of the contact person
providing the registration information. This information will enable us
to communicate with the contact person if any questions arise regarding
the IRB or its registration information, and the information now
required is similar to that required for the contact person under
OHRP's rule. We also have reorganized the provision to make it easier
to understand what information is required.
(Comment 9) Proposed Sec. 56.106(b)(3) would require IRBs to
provide the ``number of active protocols (small, medium, or large)
involving FDA-regulated products reviewed.'' The proposal explained
that a ``small'' number of protocols is 1 to 25 protocols; ``medium''
is 26 to 499 protocols, and ``large'' is 500 protocols or more.
Several comments interpreted this provision in different ways or
sought clarification as to its meaning. In brief:
One comment asked us to define ``protocol'' because it
said questions would arise regarding multi-site studies involving a
single protocol.
Another comment would redefine the numerical ranges so
that ``small'' would be 1 to 99 protocols, ``medium'' would be 100 to
499 protocols, ``large'' would be 500 to 1,999 protocols, and ``very
large,'' a new category, would be 2,000 protocols or more. The comment
explained that a ``substantial number'' of organizations oversee
thousands of protocols and that these organizations operate differently
compared to those that review 500 protocols.
Another comment expressed concern about the protocol
numbers, stating that it was unclear how useful or accurate the data
would be due to complexities in IRB review and ``protocol driven
research activities,'' the level of IRB review (such as full IRB review
or expedited review), and frequent or daily changes in protocol review
numbers.
Similarly, another comment stated that protocols are neither
uniform nor uniformly complex, so that protocol activity is not a
reasonable basis for determining IRB activity. A third comment said
that we should consider the protocol ranges to be only approximations
of IRB workloads and use the information carefully and cautiously in
evaluating or characterizing IRBs.
Another comment disputed the need for protocol review
information, arguing that compliance with regulatory requirements is an
issue regardless of the number of protocols reviewed by an IRB.
(Response) The preamble to the proposed rule explained that
information regarding the number of protocols reviewed would enable us
to determine how active an IRB is and to assign our inspection
resources based on IRB activity levels (see 69 FR 40556 at 40558). Our
intent was not to get an exact or precise figure, and the proposal's
use of ``small,'' ``medium,'' and ``large'' protocol ranges reflected
that intent.
Consequently, we decline to revise the rule to define ``protocol''
in the final rule. Webster's II--New Riverside University Dictionary
defines ``protocol,'' in relevant part, as ``the plan for a scientific
experiment or treatment'' (see Webster's II--New Riverside University
Dictionary at page 947 (1988)). Thus, in the comment's scenario, if an
IRB conducts one review for a multi-site study, that single review
could be considered as one ``protocol.'' If an IRB conducts separate
reviews for individual study sites, then it conceivably could have
reviewed multiple ``protocols'' notwithstanding the fact that the study
plan remains essentially the same for all sites.
However, on our own initiative, we have amended Sec. 56.106(b)(3)
to define what the term ``active protocol'' means. The final rule
defines ``active protocol'' as ``any protocol for which an IRB
conducted an initial review or a continuing review at a convened
[[Page 2362]]
meeting or under an expedited review procedure during the preceding 12
months.'' We have made this change to be consistent with changes made
by OHRP in its final rule.
With respect to the proposal's numerical ranges and their
usefulness to us, we reiterate that our intent was to get a general--
rather than a precise--sense of how active IRBs are and to assign our
limited inspectional resources more efficiently and effectively. We
recognize that there are different types of IRB review and that changes
in an IRB's workload could make an IRB's protocol estimate outdated or
obsolete at a later point in time. However, given the protocol ranges
were created simply to give us an idea about an IRB's activity, we have
revised the rule to eliminate the ``small,'' ``medium,'' and ``large''
ranges. Instead, the final rule requires an approximate number of
active protocols reviewed, but we neither expect nor want IRBs to
constantly change or update their protocol numbers whenever their
protocol numbers fluctuate. If the approximate number of protocols
changes after initial IRB registration, the IRB should report the new
protocol number as part of the re-registration process which takes
place every 3 years.
As for compliance activities, we believe the comment may have
misinterpreted the preamble to the proposed rule. We did not state that
we would base inspections solely on an IRB's self-reported level of
``small,'' ``medium,'' or ``large'' numbers of protocols reviewed. We
simply said that the information would help us assign inspection
resources based on IRB activity levels.
To put it another way, we have limited inspectional resources, and
our field staffs that inspect IRBs are also responsible for many other
types of inspections and activities. We must prioritize our routine IRB
inspections in some manner to make the most efficient use of our
resources. Such prioritization of IRB inspections is not tantamount to
declaring, as the comment suggests, that IRBs reviewing ``small'' or
``medium'' numbers of protocols do not have to comply with FDA
regulations or that we enforce our requirements differently depending
on whether an IRB reviews a ``small,'' ``medium,'' or ``large'' number
of protocols. Nevertheless, given that the final rule does not contain
the ``small,'' ``medium,'' or ``large'' protocol ranges, the issue is
largely moot.
(Comment 10) Proposed Sec. 56.106(b)(4) would require IRBs to
describe the types of FDA-regulated products, such as biological
products, color additives, food additives, human drugs, or medical
devices, involved in the protocols that they review.
Two comments addressed this provision. One comment stated that it
had no objection to the requirement provided that the description could
be simple or generic without numerical ranges associated with each
product type. Another comment said the descriptions would be
appropriate only if we used the information for purposes of sending
useful and targeted information to IRBs. The comment also said that the
description should be generic and without numerical ranges associated
with product types.
(Response) We agree with the comments. Section 56.106(b)(4) merely
seeks a generic description of the FDA-regulated products in the
protocols reviewed by the IRB. So, for example, if the IRB reviews
protocols for human drug studies, the description, to satisfy Sec.
56.106(b)(4), could simply be ``human drugs.'' If the IRB reviews
protocols for human drug and medical device studies, the description
would be ``human drugs'' and ``medical devices.'' We also note that the
electronic registration system will list the types of FDA-regulated
products and allow individuals to check the appropriate boxes relating
to those products and to check ``other'' and explain what the ``other''
FDA-regulated products are.
Furthermore, Sec. 56.106(b)(4) does not require IRBs to assign
numerical values to the FDA-regulated product types. As the comments
noted, our intent is to use this information to send product-specific
information to IRBs, and we can do so with a simple description of
product types.
(Comment 11) Proposed Sec. 56.106(b)(5) would require 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. The preamble to the proposed rule stated that we
recognized that IRB accreditation is a developing concept and invited
comment on ``the perceived value of collecting information on the
accreditation status of IRBs'' (see 69 FR 40556 at 40558).
We received more than 10 comments on IRB accreditation issues, and
the comments reflected a considerable difference of opinion regarding
IRB accreditation and whether we should require information about such
accreditation. In brief, the comments stated:
IRB accreditation information may give FDA useful
information in deciding which IRBs to inspect and may help us decide
whether to focus educational activities on certain areas. One comment
added that accreditation information would help us evaluate the value
of IRB accreditation. In contrast, one comment said that IRB
accreditation information will not give FDA new information that will
be useful in assessing accreditation's value;
FDA should refer to accreditation of human research
protection programs rather than accreditation of IRBs;
FDA should require information about the name of the
accrediting organization under which the IRB functions or collect
information about accreditation type or level. One comment explained
that one body has two different accreditation categories;
The additional reporting burden should not be passed on to
the institution;
FDA should delete the provision because accreditation
information can be collected without the need for a regulation or is
publicly available from accrediting organizations. One comment added
that accreditation information, if it were part of the IRB registration
requirement, might be unreliable because our rule would require re-
registration every 3 years; and
Accreditation does not accurately represent a measure of
compliance with human subject protection requirements. Similarly, an
IRB's lack of accreditation could be misconstrued as reflecting on the
quality of the IRB's human subject protection program. In contrast, one
comment strongly encouraged IRBs to become accredited, and another
comment said that accreditation implies that a certain standard has
been achieved.
(Response) The final rule omits accreditation information from the
IRB registration requirements. We agree that, if necessary, we can
obtain accreditation information from the accreditation organizations
themselves and that the resulting information may be more reliable or
accurate, given that the rule does not require certain registration
information to be updated until re-registration. We also agree that, as
a general matter, accreditation does not ensure or demonstrate that a
particular action was done correctly; instead, accreditation may
increase one's confidence that the accredited body is capable of
performing a particular action correctly.
Furthermore, we continue to believe that accreditation, insofar as
human subject protection is concerned, is still a developing concept.
Consequently, we will continue to follow such accreditation activities,
but will not require accreditation information as part of IRB
registration.
[[Page 2363]]
Finally, because the final rule does not require accreditation
information, the comment regarding reporting burdens is moot.
D. When Must an IRB Register? (Section 56.106(c))
Proposed Sec. 56.106(c) would have IRBs register once and to renew
their registrations every 3 years. Initial IRB registration would occur
within 30 days before the date when the IRB intends to review clinical
investigations regulated by FDA. IRB registration would become
effective upon HHS posting of the registration information on its Web
site.
(Comment 12) One comment would have us consider IRBs to be
registered as soon as they complete submitting the registration
information regardless of whether the IRB submitted the information
electronically or in writing. Another comment suggested that the
electronic registration system acknowledge or document that the IRB has
registered. Another comment stated that, if IRB registration is to
identify IRBs for future inspections, there is no need for a 30-day
``waiting'' period.
A different comment said that the 30-day time period might
interfere with IRB review, particularly expedited reviews and full IRB
reviews that take less than 30 days. The comment suggested that we
revise the rule so that IRBs may not issue a determination on FDA-
regulated research until they have registered.
Another comment asked us to clarify when IRBs must register. The
comment explained that the codified provision directed IRBs to submit
an initial registration within 30 days before the date when the IRB
intends to review clinical investigations regulated by FDA. The comment
said that the word ``within'' could mean that an IRB could register
``anytime between one and 30 days before reviewing a protocol,'' but
that the preamble to the proposed rule interpreted proposed Sec.
56.106(c) as requiring registration at least 30 days before reviewing
the protocol. The comment preferred giving IRBs the ability to register
any time between 1 and 30 days before reviewing protocols in FDA-
regulated research.
(Response) We agree, in part, with the comments. For IRBs that
register electronically, the registration system will notify them that
they are registered. This notification will be sent to the electronic
mail address that the IRB provides as part of the registration process.
The IRB's registration will be effective after review and acceptance by
HHS. We have amended Sec. 56.106(c) regarding the time at which IRB
registration becomes effective to correspond to changes made by OHRP in
its final rule which is published elsewhere in this issue of the
Federal Register. OHRP revised a comparable provision in its rule to
clarify when IRB registration would become effective.
For IRBs that submit their registration information in writing, our
experience with written forms in other contexts suggests that some
individuals will not complete the forms or omit required information.
As a result, we may need to contact individuals to obtain the missing
information. Therefore, it would be more practical for us to consider
IRBs who submit their registration information in writing to be
registered only after they have submitted all required registration
information, we have entered that information into the electronic
registration system, and the information is reviewed and accepted by
HHS.
As for the comments concerning the 30-day timeframe and the
suggestion that we amend the rule so that IRBs cannot issue decisions
on FDA-regulated research until they have registered, we have decided
to eliminate the 30-day timeframe from the final rule. We note that IRB
registration, alone, does not address issues regarding an IRB's
competence or expertise, nor does it require IRBs to meet a particular
standard in order to conduct a review. However, because it is important
to FDA to assemble an accurate IRB database, we have revised Sec.
56.106(c) to state that: ``Each IRB must submit an initial
registration. The initial registration must occur before the IRB begins
to review a clinical investigation described in paragraph (a) of this
section. Each IRB must renew its registration every 3 years. IRB
registration becomes effective after review and acceptance by HHS.''
(Comment 13) One comment would require IRBs to renew their
registration every year instead of every 3 years. The comment said that
3 years would be too long a time period.
(Response) We decline to revise the rule as suggested by the
comment. IRB registration does not confer any particular status on
IRBs, nor does registration, alone, reflect upon an IRB's competence or
capabilities. Moreover, given that the information we seek through IRB
registration is quite basic (as in names and addresses) and that Sec.
56.106(e) describes how and when IRBs are to revise their registration
information, annual registration would not appear to confer any
advantages or make registration information more accurate or reliable.
Consequently, we decline to require IRBs to register annually.
E. Where Can an IRB Register? (Section 56.106(e))
Proposed Sec. 56.106(e) would direct IRBs to register at a
specific Internet address or, if an IRB lacked the ability to register
electronically, to send its registration information to a specific mail
address. We indicated that we would provide the Internet address and
mail address in the final rule. We also invited comment on whether we
should discontinue written IRB registration procedures after some time
period has elapsed, because we did not know how widespread Internet
access is among IRBs (see 69 FR 40556 at 40558).
(Comment 14) Several comments pertained to the registration
site(s). One comment said we should maintain one common registration
site with OHRP and that the registration system should automatically
include currently registered IRBs. The comment said the registration
system should also allow such IRBs to retain their assigned numbers.
The comment acknowledged the intent to create a single registration
site, but implied that the proposed rule's omission of a specific
Internet address created concern. Another comment supported creation of
a simple, electronic registration system.
(Response) We agree that a single Internet registration site should
be used for electronic registrations and have always worked with OHRP
towards that end. We were unable to provide a specific Internet address
at the time of the proposed rule because the electronic registration
system was still under development. The final rule now states that the
Internet registration address is http://ohrp.cit.nih.gov/efile.
Additionally, as we stated in the preamble to the proposed rule,
OHRP will continue to recognize previous IRB registrations (see 69 FR
40556 at 40558).
(Comment 15) One comment asked whether entities that have more than
one IRB at the same location need to register more than once or whether
they could register once and provide multiple pieces of information in
connection with a single registration.
(Response) The electronic registration system will assign an
organization number to each entity, and this will enable the entity to
register several IRBs without having to enter the same data repeatedly
for each IRB.
(Comment 16) Two comments encouraged us to have the electronic
registration system consider IRBs to be registered automatically once
an IRB completes the electronic registration process or to send
acknowledgements to the IRBs once they complete the electronic
registration process.
[[Page 2364]]
(Response) As we stated in our response to comment 12 of this
document, when an IRB completes the electronic registration process and
HHS has reviewed and accepted the information, the electronic
registration system will notify IRBs that they are registered.
(Comment 17) Several comments responded to our question whether we
should discontinue written IRB registrations after some time period has
elapsed. One comment supported conversion to electronic registration as
soon as possible, but said it is important to allow small organizations
the time to acquire the necessary technology. The comment agreed that
not all institutions have electronic capabilities or Internet access.
Another comment supported giving IRBs the option to submit
registration information in writing for a predetermined period of time,
but did not suggest any time period. A different comment also supported
the written registration option, but suggested that it be available
only for 2 years.
Another comment opposed discontinuing written IRB registration. The
comment said that there are adverse consequences to both the IRB and
any sponsor or investigator that might use an unregistered IRB (which
appeared to be a reference to a later discussion, in the preamble to
the proposed rule, about ``What Happens if an IRB Does Not Register?''
(see 69 FR 40556 at 40559)), so we should continue to make written IRB
registration possible.
(Response) While we continue to believe that most IRBs will use the
electronic registration system, we do not know how many IRBs will use
the written registration option, and the administrative record for this
rulemaking does not give us sufficient basis to set a deadline at which
we would end the written registration option. (We realize that one
comment suggested a 2-year period, but, given that IRBs have 3 years to
renew registrations, discontinuing written registrations after 2 years
would not give IRBs the opportunity to renew their registrations in
writing.) Consequently, until we become more experienced with IRB
registrations, we will continue to offer written registration as an
alternative to electronic registration, and the final rule states that
IRBs that lack the ability to register electronically must send their
registration information, in writing, to the Good Clinical Practice
Program (HF-34), Office of Science and Health Coordination, Food and
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
F. How Does an IRB Revise Its Registration Information? (Section
56.106(e))
Proposed Sec. 56.106(e) would have IRBs revise their registration
information within specific timeframes if certain changes occurred. For
example, if the IRB's contact or chair person information changes,
proposed Sec. 56.106(e) would require the IRB to change its
registration information within 90 days of the change. If the IRB
decided to disband or to discontinue reviewing FDA-regulated clinical
investigations, it would report that change within 30 days. All other
information changes would be reported when the IRB renews its
registration.
(Comment 18) Two comments pointed out a discrepancy between the
proposed rule and its preamble. The comments noted that the preamble to
the proposed rule said that if an IRB reviews new types of FDA-
regulated products, it would revise its registration information within
30 days (see 69 FR 40556 at 40559), yet proposed Sec. 56.106(e) was
silent regarding such changes. The comments suggested that we reconcile
the codified text with the preamble.
(Response) The comments were correct. We inadvertently omitted
changes in the IRB's review of FDA-regulated research from proposed
Sec. 56.106(e), and we have revised the rule so that IRBs must revise
their registration information within 30 days if they review new types
of FDA-regulated products. Additionally, on our own initiative, we have
added a parenthetical phrase to clarify that a decision to review ``new
types of FDA-regulated products'' should be interpreted as a decision
to review a different category of FDA-regulated products, such as a
decision to review studies pertaining to food additives when the IRB
previously reviewed studies pertaining to drug products. We do not want
IRBs to revise their registration information if they decide to review
studies pertaining to subcategories within the same class of FDA-
regulated products; for example, if an IRB previously reviewed studies
pertaining to drugs intended to treat cardiac conditions and then
decided to review studies pertaining to drugs intended to treat cancer,
both types of studies would still pertain to drug products, so there
would be no ``new type'' of FDA-regulated product within Sec.
56.106(e).
(Comment 19) One comment addressed IRBs that have decided to
disband. The comment said that the process of closing an IRB may take
longer than 30 days, so requiring IRBs to revise their registration
information within 30 days of a decision to disband would put an
``undue burden'' on IRBs and the institutions responsible for the IRBs.
(Response) We agree in part, and disagree in part with the comment.
We agree that, in some cases, closing an IRB may take more than 30
days, but, in other cases, the process may take less time. In other
words, IRBs vary in size, resources, organization, and complexity, and,
as a result, different IRBs will take different amounts of time to
perform the same or similar functions.
The comment also may have misinterpreted the proposed rule.
Proposed Sec. 56.106(e) stated that an IRB's decision to disband or to
discontinue reviewing FDA-regulated clinical investigations is a change
that must be reported within 30 days of that change; thus, the proposal
would begin the time period when IRB decides to close, not when the IRB
finally closes. Nevertheless, for consistency with OHRP's final rule
(which appears elsewhere in this issue of the Federal Register), we
have revised Sec. 56.106(e) to state that an IRB's decision to disband
is a change that must be reported ``within 30 days of permanent
cessation of the IRB's review of research.'' In the preamble to the
OHRP final rule, OHRP states that ``the date of permanent cessation of
the IRB's review of * * * research would occur on or after the IRB's
decision to disband, but not before the IRB's decision to disband was
made.''
Furthermore, given the simplicity of the electronic registration
system, we do not believe that IRBs or their institutions will find it
``unduly'' burdensome to report the IRB's decision to disband.
(Comment 20) One comment would shorten the time period for
reporting changes in the IRB's contact or chair person information from
90 days to 60 days.
(Response) We decline to revise the rule as suggested by the
comment. The comment did not identify any advantage in shortening the
timeframe, and we do not believe that reducing the timeframe by 30 days
will confer any significant benefit.
G. What Other Comments Did We Receive?
1. What Information Will Be Publicly Available?
The preamble to the proposed rule referred to the OHRP proposal for
information regarding public disclosure of IRB registration
information, the Freedom of Information Act (FOIA), and
[[Page 2365]]
the Privacy Act of 1974 (see 69 FR 40556 at 40557). It also stated
that, insofar as FDA's registration system was concerned, the name of
the institution operating the IRB and the IRB's name will be publicly
accessible, and all other IRB registration information would be subject
to public disclosure under FOIA and our public information regulations
at part 20 (21 CFR part 20) (see id.).
(Comment 21) One comment said that, in addition to the
institution's name and the IRB's name, we should make the following
information publicly available:
The name, address, and telephone number of the IRB
contact; and
For accredited IRBs, information relating to that
accreditation.
Another comment asked us to clarify what information would be
publicly available under FOIA.
(Response) All registration information required under this rule
will be subject to FOIA and any other applicable statutes and
regulations pertaining to public disclosure. Please note that certain
information may be withheld from public disclosure or may require an
individual's consent to public disclosure (see, e.g., Sec. 20.63(e)
(stating that a request for all records relating to a specific
individual will be denied as a clearly unwarranted invasion of personal
privacy unless accompanied by the written consent of the individual
named)).
As for accreditation information, accreditation status is not
required under the final rule, so that information will not be publicly
available from us or from OHRP.
(Comment 22) One comment suggested that sponsors and investigators
have access to the IRB registration database. The comment said that
sponsors and investigators currently have access to Federal-wide
assurances data and suggested that, if sponsors and investigators could
not have access to the IRB registration database, we or OHRP should
issue a report of IRB registrations or issue certificates to individual
IRBs.
(Response) OHRP currently posts all registered IRBs on its Web
site, including the name and location of the organization operating the
IRB(s) and the name and location of each IRB.
We decline to issue reports on IRB registration or certificates to
show that an IRB is registered. As we stated in our response to comment
12 of this document, IRB registration, alone, does not address issues
regarding an IRB's competence or expertise, nor does it require IRBs to
meet a particular standard in order to conduct a review.
(Comment 23) One comment said we should establish a link to the
publicly available IRB registration information from the portion of our
own Web site that pertains to ``Good Clinical Practices in FDA-
Regulated Clinical Trials,'' located at http://www.fda.gov/oc/gcp/
default.htm.
(Response) We agree with the comment and have modified our Web site
accordingly.
2. What Happens if an IRB Does Not Register?
The preamble to the proposed rule stated that sponsors and
investigators who used unregistered IRBs might be using IRBs that
``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'' (see 69 FR 40556 at 40559). Thus, the
preamble to the proposed rule added that, ``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'' (id.).
The preamble to the proposed rule also noted how we considered
other options to require sponsors and investigators to use only
registered IRBs, such as refusing 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 (id.). The
preamble to the proposed rule also invited comment on what sanctions or
administrative mechanisms, if any, should or might be used against
sponsors and investigators who use unregistered IRBs and whether any
additional changes to our regulations were necessary.
(Comment 24) We received many comments relating to sanctions, other
regulatory changes, and ensuring that sponsors and investigators use
only registered IRBs. The comments reflected a considerable difference
of opinion. For example:
One comment said we should impose and enforce ``high
fines'' for failure to follow human subject protection regulations;
Several comments said that the forms investigators
currently use (Form FDA 1572) could be used to reinforce or otherwise
highlight the need to use only registered IRBs, but the comments
differed as to whether investigators should be subject to any sanctions
if they use an unregistered IRB. For example, one comment said failure
to use a registered IRB should be treated the same as any other breach
of an investigator's responsibilities, but others said that IRBs,
rather than sponsors or investigators, should be responsible for any
failure to register. One comment also opposed placing an investigation
on clinical hold because, the comment argued, clinical holds are
appropriate when the rights and/or safety of human subjects are in
jeopardy or other material, noncompliance concerns are evident; the
comment said that failure to register does not mean improper oversight
by the IRB or by the sponsor. Some comments argued that sponsors and
investigators should not be obliged to monitor an IRB's registration
status. In contrast, one comment would have us amend the
investigational new drug (IND) application regulations to authorize us
to place a study on clinical hold if the sponsor or investigator uses
an unregistered IRB. The same comment suggested that we consider
additional enforcement options, such as ``refusing 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.''
Several comments, mostly from pharmaceutical firms or
trade associations, opposed any changes outside the IRB regulations.
The comments, in general, felt that the existing IND regulations were
sufficient and clear regarding a sponsor's or investigator's obligation
to use IRBs that comply with part 56. Some comments said we should not
expend resources on revising the IND regulations but should promote
awareness of the IRB registration requirements instead. Another
comment, from an association of medical colleges, also opposed
revisions to the IND regulations, stating that clinical holds would be
unworkable because, if an unregistered IRB had reviewed a clinical
study and the clinical study had proceeded, retroactive review of the
study would be impermissible. The comment said we should refuse to
consider information from an application for a research permit that is
reviewed or is to be reviewed by an unregistered IRB.
One comment suggested a ``flexible'' approach whereby we
would start by sending a certified letter to an unregistered IRB
regarding its failure to register and include registration
instructions. If the IRB remained unregistered, the comment suggested
that we inspect the IRB. The comment said that this approach would
allow us to take appropriate action against unregistered IRBs without
``unnecessarily penalizing'' sponsors and investigators who have
attempted to
[[Page 2366]]
follow our regulations in good faith. Similarly, another comment
advocated sending letters to IRBs or notices to sponsors rather than
imposing sanctions.
One comment agreed with us that an IRB's failure to
register would not justify disqualification of the IRB under Sec.
56.121 absent the extreme circumstances described in Sec. 56.121(b)(1)
(the IRB has refused or repeatedly failed to comply with regulatory
requirements) or Sec. 56.121(b)(2) (the noncompliance adversely
affects the rights or welfare of the human subjects in a clinical
investigation).
(Response) We agree in part and disagree in part with the comments.
We agree that the existing IND regulations, as well as the IDE
regulations, are sufficient and clear regarding a sponsor's or
investigator's obligation to use IRBs that comply with part 56. We also
agree that an IRB's failure to register, alone, should not lead to
disqualification proceedings under Sec. 56.121 absent extreme
circumstances. We intend to educate IRBs, sponsors, and investigators
about the IRB registration requirements and to encourage sponsors and
investigators to use registered IRBs for the same reasons we stated in
the preamble to the proposed rule.
Given the existing IND and IDE regulations and our intent to pursue
educational efforts, we disagree with those comments that would have us
impose fines or place clinical investigations on clinical hold if the
sponsor or investigator used an unregistered IRB. We believe that it
would be premature for us to consider the use of such sanctions before
we and the regulated community have gained sufficient experience with
the IRB registration program.
3. What Other Issues Did the Comments Raise?
Several comments addressed issues that were either not part of the
rulemaking or not material to the proposed codified text.
(Comment 25) One comment disagreed with the preamble to the
proposed rule when we stated that our knowledge about the identities
and numbers of IRBs reviewing FDA-regulated clinical research is
obsolete or incomplete (see 69 FR 40556 at 40557). The comment said
that we require sponsors to identify IRBs and that, for 20 years, OHRP
has maintained a list of IRBs that have filed assurances (under 45 CFR
part 46). The comment said that such past practices were apparently
sufficient for purposes of conducting inspections.
(Response) We disagree with the comment. As we stated in the
preamble to the proposed rule, existing FDA regulations have required
some, but not all, clinical investigators and sponsors to provide IRB
names and addresses to us, and those regulatory requirements differ
slightly (see 69 FR 40556 at 40557). Consequently, because of
differences within our own regulations, we do not have a comprehensive
list of IRBs that review FDA-regulated research. Additionally, because
our pre-existing regulations do not require sponsors and investigators
to revise or update IRB information if and when the IRB changes its
address, contact person, or chair person, or even, in some cases, to
provide addresses, contact information, or chair person information to
us, the IRB information we do have is not as detailed as the
information we seek under this rule.
As for institutions that have filed assurances with OHRP under 45
CFR part 46, the IRBs associated with such institutions are not
necessarily identical to those that review FDA-regulated research.
OHRP's regulations apply to institutions that are engaged in human
subjects research conducted or supported by HHS. In contrast, our IRB
regulations apply to clinical investigations regulated by us,
regardless of whether those investigations are conducted or supported
by HHS. Thus, the fact that OHRP has operated an assurance system for
decades does not necessarily mean that the OHRP list of institutions
that have filed assurances can serve as a list of IRBs that review FDA-
regulated research.
(Comment 26) One comment said that registration and re-registration
fees should be set at $5,000 to cover costs. The comment said that
taxpayers should not have to pay the fees or fund the costs of
``profiteers,'' and that pharmaceutical companies should not ``get
away'' with low fees when ``they can pay their executives $150,000,000
at retirement.''
(Response) We decline to revise the rule as suggested by the
comment. We have no express authority to impose registration or re-
registration fees on IRBs. Additionally, the rule is directed at IRBs
themselves rather than pharmaceutical firms, so issues relating to
pharmaceutical executives' salaries are not relevant to this
rulemaking.
(Comment 27) One comment asked us to confirm that our IRB
inspections will adhere to the guidelines described in the ``Guidance
for Institutional Review Boards and Clinical Investigators.''
(Response) This rulemaking does not affect how we conduct IRB
inspections. We may, however, use IRB registration information to help
us prioritize inspections. Additionally, our receipt of more accurate
IRB addresses and contact information due to IRB registration should
make it easier and more efficient to schedule IRB inspections.
H. What Other Amendment Did We Propose?
The proposal would also make a non-substantive 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 its reference to 21 CFR part 813. The preamble to the
proposed rule explained that this change is necessary because we
removed the regulations at part 813 (which had pertained to intraocular
lenses) in 1997 (see 62 FR 4164, January 29, 1997).
We received no comments on this aspect of the proposal.
Consequently, the final rule deletes a reference to part 813.
III. Implementation
This rule is effective July 14, 2009. This protracted effective
date is necessary to allow refinement of the electronic registration
system so that it corresponds to this final rule and to OHRP's final
rule.
IV. Legal Authority
In general, the act authorizes us to issue regulations pertaining
to investigational uses of FDA-regulated products (see, e.g., sections
409(j) (21 U.S.C. 348(j)) (investigations involving food additives);
505(i) (investigations involving human drugs); 520(g) (investigations
involving devices); and 721(f) (21 U.S.C. 379e(f)) of the act
(investigations involving color additives)).
The act also requires the submission of a petition or application
to FDA (see, e.g., sections 409(b) (food additive petitions); 505(b)
(new drug applications); 505(j) (abbreviated new drug applications);
513(f) (premarket notification for devices); 515(c) (premarket approval
applications for devices); 520(m) (humanitarian device exemption
applications); and 721(b) of the act (color additive petitions)) before
marketing begins.
To implement these provisions of the act, section 701(a) of the act
gives us the authority to issue regulations for the efficient
enforcement of the act. By requiring IRB registration, the final rule
will aid in the efficient enforcement of the act's provisions regarding
the
[[Page 2367]]
investigational use of various FDA-regulated products (because then we
would be able to conduct IRB inspections more efficiently) as well as
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 final rule will 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. Consequently, we conclude that we have sufficient legal
authority to issue the final rule.
V. Economic Impact Analysis
We have examined the impacts of the final rule under Executive
Order 12866, 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). The agency believes that
this final rule is not a significant regulatory action as defined by
the Executive Order.
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because the required registration information is
minimal and the costs associated with registration are low, the agency
certifies that the final rule will not have a significant economic
impact on a substantial number of 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 the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $127 million, using the most current (2006) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
final rule to result in any 1-year expenditure that would meet or
exceed this amount.
The final rule requires most IRBs to register with FDA. The
information sought through the registration process is minimal,
consisting largely of names and addresses for a contact person, the
institution operating the IRB (if an institution exists), the head of
the institution, the IRB, and the IRB chairperson. The registration
would also indicate the approximate number of active protocols reviewed
and the types of FDA-regulated products involved. We estimate that
initial IRB registration may require 1 hour. The average loaded wage
rate for administrators at public institutions is about $44 per
hour.\1\ This means that each IRB would spend $44 for an initial
registration ($44 per hour x 1 hour per initial registration).
---------------------------------------------------------------------------
\1\ Source: United States Department of Labor, Bureau of Labor
Statistics; National Compensation Survey, June 2005. Overall hourly
rate in the United States for administrators and officials, public
administration, is $31.54. To account for benefits, the hourly rate
was increased by 40 percent and rounded to the nearest whole dollar.
Data accessed on August 31, 2006, at http://data.bls.gov.
---------------------------------------------------------------------------
We estimate that re-registration would require less time,
especially if the IRB verifies existing information. If re-registration
requires 30 minutes, then the cost of re-registration to each IRB would
be approximately $22 ($44 per hour x 0.5 hours per re-registration).
Revising an IRB's registration information would probably involve
costs similar to re-registration costs. If the revision requires 30
minutes, then the cost of revising an IRB's registration information
would be approximately $22 per IRB.
Given the minimal registration information that would be required
and the low costs associated with registration, this final rule is not
a significant regulatory action, and we certify that the final rule
does not have a significant economic impact on a substantial number of
small entities. Therefore, the rule 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 final rule will result in a 1-year expenditure of $220,000 (5,000
IRBs x $44 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, we are not required to perform a cost-benefit
analysis under the Unfunded Mandates Reform Act.
VI. Environmental Impact
We have 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 1990
This rule contains information collection requirements that are
subject to review by the Office of Management and Budget (OMB) under
the Paperwork Reduction Act of 1995 (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.
Title: Institutional Review Boards: Registration Requirements.
Description: The final rule requires IRBs to register with FDA.
Description of Respondents: Businesses and individuals.
The estimated burden associated with the information collection
requirements of this rule is 8,750 hours.
We estimate the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of Annual Frequency Total Annual Hours per
21 CFR Section Respondents per Response Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
56.106(c) (initial 5,000 1 5,000 1 5,000
registration)
----------------------------------------------------------------------------------------------------------------
56.106(c) (re-registration) 2,500 1 2,500 0.5 1,250
----------------------------------------------------------------------------------------------------------------
[[Page 2368]]
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.
Our 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
(see Department of Health and Human Services, Office of the Inspector
General, Institutional Review Boards: A Time for Reform, page 3, June
8, 1998). While not all IRBs are involved in clinical investigations
regulated by FDA, for purposes of the PRA, we will use 5,000 as the
maximum number of IRBs subject to the final rule. Additionally, because
the final rule requires basic information about an IRB (such as names
and addresses) and because registration would, in most cases, be done
electronically, we 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).
Re-registration and revisions to existing registration information
should require less time than initial registration. We will assume that
re-registration and revisions will take only 30 minutes per IRB. We
will also assume, based on OHRP's experience with its IRB registration
program, that 50 percent of IRBs (2,500) will re-register and that all
(5,000) will revise their registration information. Therefore, the
total burden hours for re-registration 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).
Prior to the effective date of this final rule, FDA will publish a
notice in the Federal Register announcing OMB's decision to approve,
modify, or disapprove the information collection provisions in this
final rule. In compliance with the PRA (44 U.S.C. 3507(d)), we have
submitted the information collection requirements of this rule to OMB
for review. An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it displays
a currently valid OMB control number.
VIII. Federalism
We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. We have 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, we have concluded that the
rule does not contain policies that have federalism implications as
defined in the order and, consequently, a federalism summary impact
statement isnot required.
List of Subjects in 21 CFR Part 56
Human research subjects, Reporting and recordkeeping requirements,
Safety.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner, part 56 is amended as follows:
PART 56--INSTITUTIONAL REVIEW BOARDS
0
1. The authority citation for 21 CFR part 10 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]
0
2. Amend Sec. 56.102 in paragraph (b)(12) by removing the phrase
``parts 812 and 813'' and by adding in its place the phrase ``part
812''.
0
3. Add Sec. 56.106 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 sections 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. All
other IRBs may register voluntarily.
(b) What information must an IRB register? Each IRB must provide
the following information:
(1) The name, mailing address, and street address (if different
from the 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, mailing address, street address (if different
from the mailing address), phone number, facsimile number, and
electronic mail address; each IRB chairperson's name, phone number, and
electronic mail address; and the name, mailing address, phone number,
facsimile number, and electronic mail address of the contact person
providing the registration information.
(3) The approximate number of active protocols involving FDA-
regulated products reviewed. 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; and
(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.
(c) 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 described in paragraph (a) of this
section. Each IRB must renew its registration every 3 years. IRB
registration becomes effective after review and acceptance by HHS.
(d) 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
[[Page 2369]]
registration information, in writing, to the Good Clinical Practice
Program (HF-34), Office of Science and Health Coordination, Food and
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
(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 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 is a change that
must be reported within 30 days of the change. An IRB's decision to
disband is a change that must be reported within 30 days of permanent
cessation of the IRB's review of research. All other information
changes may be reported when the IRB renews its registration. The
revised information must be sent to FDA either electronically or in
writing in accordance with paragraph (d) of this section.
Dated: January 7, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-682 Filed 1-14-09; 8:45 am]
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