[Federal Register Volume 71, Number 109 (Wednesday, June 7, 2006)]
[Rules and Regulations]
[Pages 32827-32834]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-8790]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 50
RIN 0910-AC25
[Docket No. 2003N-0355]
Medical Devices; Exception From General Requirements for Informed
Consent
AGENCY: Food and Drug Administration, HHS.
ACTION: Interim final rule.
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SUMMARY: The Food and Drug Administration (FDA) is issuing this interim
final rule to amend its regulations to establish a new exception from
the general requirements for informed consent, to permit the use of
investigational in vitro diagnostic devices to identify chemical,
biological, radiological, or nuclear agents without informed consent in
certain circumstances. The agency is taking this action because it is
concerned that, during a potential terrorism event or other potential
public health emergency, delaying the testing of specimens to obtain
informed consent may threaten the life of the subject. In many
instances, there may also be others who have been exposed to, or who
may be at risk of exposure to, a dangerous chemical, biological,
radiological, or nuclear agent, thus necessitating identification of
the agent as soon as possible. FDA is creating this exception to help
ensure that individuals who may have been exposed to a chemical,
biological, radiological, or nuclear agent are able to benefit from the
timely use of the most appropriate diagnostic devices, including those
that are investigational.
DATES: This rule is effective June 7, 2006. Submit written or
electronic comments by August 7, 2006.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
FOR FURTHER INFORMATION CONTACT: Claudia M. Gaffey, Center for Devices
and Radiological Health (HFZ-440), Food and Drug Administration, 2098
Gaither Rd., Rockville, MD 20850, 240-276-0496, ext. 109.
SUPPLEMENTARY INFORMATION:
[[Page 32828]]
I. Background
U.S. Federal, State, and local authorities have developed and are
refining a comprehensive public health plan to prepare for, and respond
to, the threat of terrorism and other potential public health
emergencies. A critical element in responding to such emergencies is
the ability to correctly and quickly identify the chemical, biological,
radiological, or nuclear agents that may have caused, or may cause,
human disease or injury. The devices included within the scope of this
rule are those for the detection of agents that have the potential to
be used in acts of chemical, biological, radiological, or nuclear
terrorism, or that can lead to other potential public health
emergencies. Examples of these agents include Bacillus anthracis
(anthrax); Yersinia pestis(plague); ricin (a lethal chemical agent);
and cobalt-60, a radiological material that could be used to build a
dirty bomb. Although it is not possible to provide an all inclusive
list of etiological agents that would be identified under conditions
that meet the criteria described in this rule, critical biologic agents
such as Category A Diseases/Agents (available at http://www.bt.cdc.gov/agent/agentlist-category.asp) or specific chemical agents (http://www.bt.cdc.gov/chemical/) that are used by the federal government for
regulatory and emergency planning purposes, may serve as examples of
the types of agents within the scope of this rule. Select agents as
defined in 42 CFR 73.1, that would suggest a terrorism event or other
public health emergency, may be considered as other examples. Most in
vitro diagnostic devices used to identify such agents have been
developed (and more are under development) by the Centers for Disease
Control and Prevention (CDC), and the Department of Defense (DOD). Some
nongovernment entities are also developing such in vitro diagnostic
devices. In most instances, these are the only devices available to
provide timely diagnostic information on the identity of these agents,
although they may not yet have been approved or cleared by FDA.
Many of these devices have not yet been approved or cleared by FDA
because clinical studies involving devices used for the identification
of such agents frequently cannot be conducted. Studies may not be
possible because natural exposure to these agents is rare or never
occurs, and there may not be enough exposed subjects to enroll in a
study. Studies also may not be possible because it is not ethical to
expose healthy human volunteers to a life-threatening toxic substance
or organism to determine the ability of the unapproved diagnostic
device to correctly identify the agent. While these unapproved devices
may not have been evaluated on specimens collected from human subjects,
testing (procedural) validation and other analytical studies generally
have been conducted (or are being conducted) by the sponsors.
Some of these devices may be under clinical investigation, while
others may not have reached that stage of development. For purposes of
this rule we are considering the term ``investigational device'' to
include those devices being evaluated in a clinical investigation as
well as those that are undergoing preclinical and/or analytical
evaluation.
Given all of these facts, the agency believes that the use of these
investigational diagnostic devices in limited circumstances is
justified when the devices are needed to identify the causative agent
in a potential public health emergency and thereby enable authorities
to promptly provide appropriate care to those exposed, and to provide
preventive therapies (if available) to others in the affected
geographic region(s).
Under FDA's regulations informed consent must be obtained before an
investigational in vitro diagnostic device may be used unless an
exception under part 50 (21 CFR part 50) applies. Institutional review
board (IRB) review and approval is also required, unless an exception
under part 56 (21 CFR part 56) applies. Under the IRB regulations
investigations may be reviewed by an IRB through a joint review
process, reliance upon the review of another qualified IRB (e.g., at
the research site, a central IRB, an independent or commercial IRB), or
similar arrangements. (See 21 CFR 56.114.) Therefore, absent an
applicable exception, investigational in vitro diagnostic devices used
to identify chemical, biological, radiological, or nuclear agents in
human specimens may only be used after obtaining informed consent from
each subject whose specimen is tested, and with IRB review and
approval.
If a terrorism event (such as dissemination of B. anthracis spores
in the mail system in 2001) or other potential public health emergency
occurs (such as the multistate outbreak of monkeypox in persons exposed
to pet prairie dogs in 2003), the timely identification of the
etiological agent may be critical to the lives of the affected subjects
as well as to the general population who may also have been exposed.
The risk to subjects and others exposed could be life-threatening, and
difficult to assess and address without the use of these
investigational devices. Identification of the agent could be delayed
significantly or precluded while the investigator seeks to obtain
informed consent. Also, in some cases, storing the specimen while
awaiting consent could have an adverse effect on the specimen and
compromise the test results. The consequences of delay could be
catastrophic for subjects and for public health in general.
Consider the following possible scenario in which a terrorist event
is not suspected until a public health laboratory cultures an unusual
or rare organism. When a patient presents to a health care facility
with symptoms suggesting a systemic microbial infection, blood and
other specimens are typically collected to determine the identity of
the causative organism. The clinical laboratory would determine that
the specimens contain an unusual organism that cannot be identified by
the tests available in that laboratory. Because many clinical
laboratories do not have the capability or resources to identify
unusual organisms or those to which humans are rarely exposed
naturally, the organism (culture isolate) or collected specimen would
be referred to a public health laboratory. The public health laboratory
would use in vitro diagnostic devices, including those that are
investigational, to try to identify the cultured organism or detect its
presence directly in the specimen.
In this scenario, the referring laboratory would not have obtained
informed consent when the specimen was collected because the person
directing that the specimen be collected would not have known at the
time that the infecting organism could be reliably identified only by
using an investigational device. To obtain informed consent would
require a number of steps and introduce unacceptable delays. The public
health laboratory would have to contact the referring laboratory that
collected the specimen or the physician who ordered the cultures in
order to locate the subject (or the subject's legally authorized
representative). Once located, the subject or the subject's legally
authorized representative would need to be contacted, provided the
informed consent information, and given the opportunity to ask
questions and sign the informed consent document. The referring
laboratory or health care facility would then have to notify the public
health laboratory that informed consent had been obtained.
[[Page 32829]]
Only at that point could testing be performed.
The scenario described in the previous paragraph is one example and
is not the only set of circumstances in which this exception to
informed consent might apply. The new exception would also apply if the
event were not terrorism-related but was another type of potential
public health emergency, such as sporadic outbreaks resulting from the
spread of an emerging infectious agent that has the potential to cause
a life-threatening situation, as in the case of Severe Acute
Respiratory Syndrome (SARS) or the potential for a pandemic influenza
virus strain. This rule would not apply in a situation which is not
life-threatening or where there is a cleared or approved available
alternative method of diagnosis that provides an equal or greater
likelihood of saving the life of the subject, such as the in vitro
diagnostic devices for identifying agents causing certain known
sexually transmitted diseases such as Chlamydia trachomatis, Neisseria
gonorrhoeae, human papillomavirus, human immunodeficiency virus, etc.
The emergency nature of the event may or may not be suspected at the
time the specimen is collected, and the laboratory involved may or may
not be a public health laboratory. Finally, even if the nature of the
event is suspected, the person collecting the specimen may not know the
investigational status of the in vitro diagnostic device and thus would
not know that informed consent should be obtained from the patient.
These variables are examples and are not meant to be the exclusive
circumstances in which this rule might apply. The exception has been
constructed in somewhat general terms because we can not anticipate the
circumstances of every emergency involving a chemical, biological,
radiological, or nuclear agent that may occur.
The process for obtaining informed consent in the scenarios
described previously would introduce dangerous delays or could
compromise the effectiveness of the testing. This process would delay
not only the diagnosis and possibly lifesaving treatment of the
subject, but would also delay recognition of a terrorism event or other
public health emergency, with serious public health consequences.
To avoid potentially dangerous delays in using investigational in
vitro diagnostic devices to identify these agents, FDA is creating a
new limited exception, within the restrictions of section 520(g)(3)(D)
of the act (21 U.S.C. 360j(g)(3)(D)), from the requirement of informed
consent. The exception applies to investigational in vitro diagnostic
tests used to identify agents, when a specimen is collected without the
recognition that an investigational test will have to be used.
II. Current Exceptions From the General Requirements for Informed
Consent
Two exceptions from the general requirements for informed consent
are described in Sec. 50.23. Section 50.23(a) provides that informed
consent shall be deemed feasible unless, before use of the test
article, both the investigator and a physician who is not otherwise
participating in the clinical investigation certify in writing all of
the following: The human subject is confronted by a life-threatening
situation necessitating the use of the test article; informed consent
cannot be obtained from the subject because of an inability to
communicate with, or obtain legally effective consent from, the
subject; time is not sufficient to obtain consent from the subject's
legally authorized representative; and there is available no
alternative method of approved or generally recognized therapy that
provides an equal or greater likelihood of saving the life of the
subject. An inability to communicate in the context of Sec. 50.23(a)
means that the subject is in a coma or unconscious. (See 46 FR 8942 at
8946, January 27, 1981). Section 50.23(d) states that, under 10 U.S.C.
1107(f), the President may waive the prior informed consent requirement
for the administration of an investigational new drug to armed forces
personnel in connection with the personnel's participation in a
particular military operation. The waiver is based on a finding by the
President that obtaining consent is not feasible, is contrary to the
best interests of the military personnel, or is not in the interests of
national security (64 FR 54180, October 5, 1999). Currently FDA is re-
examining this regulation in light of the recent amendment of 10 U.S.C.
1107 by the Ronald W. Reagan National Defense Authorization Act for
Fiscal Year 2005 which changed the criteria that may be used by the
President for waiving informed consent.
In addition, Sec. 50.24 provides an exception from the informed
consent requirements for emergency research. Section 50.24 is intended
to permit the study of potential improvements in the treatment of life-
threatening conditions where current treatment is unproven or
unsatisfactory, in order to improve interventions and patient outcomes.
The exception applies to limited research activities involving human
subjects who are in need of emergency medical intervention, but cannot
give informed consent because of their medical condition. (See 61 FR
51498 at 51499, October 2, 1996.) Section 50.24 is intended to be used
in circumstances that are different than those described in this rule,
i.e., planned clinical research of a specific investigational article
that will be studied in a specific class of patients.
The situation described in this document does not meet the
requirements of the current exceptions from the general requirements
for informed consent in Sec. 50.23. It does not satisfy the
requirements of Sec. 50.23(a) because the subject may be physically
able to provide informed consent. It does not satisfy the requirements
of Sec. 50.23(d) because that exception applies only to administration
of investigational drugs to military personnel by DOD. In addition,
Section 50.24 is generally not applicable because, in the situations
addressed in that section, subjects are not able to consent because of
their medical condition. In contrast, in the situations addressed in
this document, it is not the condition of the subject that prevents the
subject from giving informed consent, but rather the fact that, by the
time it is known that the laboratory needs to use an investigational
device to identify the etiological agent, the subject is physically
separated from the specimen, and there is not enough time to locate the
subject or the subject's legally authorized representative and obtain
informed consent.
III. Revisions
FDA is creating a new exception from the general requirements for
informed consent to address situations associated with preparing for,
and responding to, chemical, biological, radiological, or nuclear
terrorism or other potential public health emergencies. The exception
applies when investigational in vitro diagnostic devices are used and
the investigator is unable to obtain timely informed consent from
subjects (or their legally authorized representatives) whose specimens
are being tested. The new limited exception is applicable only when it
is not feasible to obtain informed consent because, at the time the
specimen is collected, it may not be known that an investigational
device would need to be used on that specimen, and delay in diagnosis
could be life-threatening to the subject.
This exception is contingent on several determinations that must be
made before using the investigational device, and later certified in
writing, by
[[Page 32830]]
both the investigator and, if time permits, by a physician who is not
otherwise participating in the clinical investigation. These
determinations are:
The human subject is confronted with a life-threatening
situation necessitating the use of the investigational in vitro
diagnostic device;
Informed consent cannot be obtained from the subject
because:
1. There was no reasonable way for the person directing that the
specimen be collected to know at the time the specimen was collected,
that there would be a need to use the investigational device on that
specimen and;
2. Time is not sufficient to obtain consent from the subject
without risking the life of the subject;
Time is not sufficient to obtain consent from the
subject's legally authorized representative; and
There is no available alternative approved or cleared
method of diagnosis to identify the chemical, biological, radiological,
or nuclear agent that provides an equal or greater likelihood of saving
the life of the subject.
Under this interim final rule, the investigator has 5 working days
after using the investigational device to submit to the IRB these
determinations as well as the review and evaluation of an independent
licensed physician. However, if, in the opinion of the investigator,
there is not sufficient time to obtain the determination of an
independent licensed physician in advance of using the investigational
device, the independent physician is required to review and evaluate
the determinations of the investigator and the investigator is required
to submit this documentation to the IRB within 5 working days after
using the device.
Until the investigational in vitro diagnostic device is used, it
will not be known whether there has been actual exposure to a chemical,
biological, radiological, or nuclear agent and whether that agent is
life-threatening. Nonetheless, FDA believes the possibility of such
exposure itself represents a life-threatening situation for the subject
because, until the investigational in vitro diagnostic device is used,
it is unknown to what agent, if any, the subject has been exposed or
how the subject should be treated.
FDA expects that in accordance with routine clinical practice, the
investigator will provide the test results obtained using the
investigational in vitro diagnostic device to the subject's health care
provider and that the results will be used in the clinical management
of the human subject. It is possible that, in certain circumstances,
the test results will also be reported to the appropriate public health
authorities. This reporting will occur when appropriate and/or required
by State or Federal law. Under the regulation, at the time the result
of the test is reported (whether to the subject's health care provider
and/or to the appropriate public health officials), the investigator is
required to disclose the investigational status of the device used to
perform the diagnostic test.
The investigator is also responsible for providing the IRB with the
information required in Sec. 50.25, the elements of informed consent,
and the procedures that will be used to provide this information to
each subject or to the subject's legally authorized representative.
Section 50.25(a) requires that the following information be provided to
each subject:
A statement that the study involves research and an
explanation of its purposes and the expected duration of the subject's
participation;
A description of the procedures to be followed, and
identification of any procedures which are experimental;
A description of any reasonably foreseeable risks or
discomforts to the subject;
A description of any benefits to the subject or others
which may be reasonably expected from the research;
A disclosure of appropriate alternative procedures or
courses of treatment, if any, that might be advantageous to the
subject;
A statement of the extent, if any, to which
confidentiality of records identifying the subject will be maintained
and that notes the possibility that FDA may inspect the records;
For more than minimal risk research, an explanation as to
whether any compensation and an explanation as to whether any medical
treatments are available if injury occurs and, if so, what they consist
of, or where further information may be obtained; and
An explanation of whom to contact for answers to pertinent
questions about the research and research subjects' rights, and whom to
contact in the event of a research-related injury to the subject.
Section 50.25(b) requires this additional information when it is
appropriate:
A statement that the particular treatment or procedure may
involve risks to the subject (or to the embryo or fetus, if the subject
is or may become pregnant) which are currently unforeseeable;
Anticipated circumstances under which the subject's
participation may be terminated by the investigator without regard to
the subject's consent;
Any additional costs to the subject that may result from
participation in the research;
The consequences of a subject's decision to withdraw from
the research and procedures for orderly termination of participation by
the subject;
A statement that significant new findings developed during
the course of the research which may relate to the subject's
willingness to continue participation; and
The approximate number of subjects involved in the study.
This information will be provided at the time the test results are sent
to the subject's health care provider and to public health authorities,
if public health reporting is required by Federal, State, or local law.
In this rule, we are requiring investigators to provide all
information described in Sec. 50.25 except the information in Sec.
50.25(a)(8) concerning voluntary participation. Normally under the
regulations subjects voluntarily agree to participate in research
before the research begins. In the circumstances covered by this rule,
an individual provides a specimen for diagnostic testing without the
knowledge of either the patient or the physician that an
investigational in vitro diagnostic (IVD) will be necessary. When the
investigational IVD is used at a setting remote from the patient and
treating physician in this case, it is not practicable (because of the
time and distance involved to contact the patient or the patient's
legally authorized representative) to obtain consent for the use of the
device. Under this rule, by the time the patient is informed that an
investigational device has been used to test his/her specimen, the
investigation is already underway, and the time at which a subject
would normally consent to voluntary participation has past. Therefore,
the investigator is not responsible for providing the information
described in Sec. 50.25(a)(8) concerning voluntary participation. In
addition, subjects or their legally authorized representatives will not
be entitled to withdraw previously collected data from the research
database, because it is critical that FDA obtain and have available for
review all data on the investigational in vitro diagnostic device's use
in order to determine whether it is safe and effective. As a result, it
is the responsibility of the IRB to ensure the adequacy of the
information required in Sec. 50.25 (except for the requirements
[[Page 32831]]
under Sec. 50.25(a)(8)) concerning voluntary participation) and to
ensure that procedures for providing this information to the subject or
the subject's legally authorized representative are in place. The IRB
is responsible for this even if an exception under Sec. 56.104(c)
exists under which the emergency use of the test article would be
reported to the IRB within 5 working days. We recognize that, in this
situation, the IRB may be delayed in assuring that these procedures are
in place.
IV. Applicability of 45 CFR Part 46 and Other Legal Requirements
According to the Office for Human Research Protection (OHRP) in the
Department of Health and Human Services (HHS), some of the activities
described in this rule may also constitute non-exempt human subjects
research within the meaning of 45 CFR part 46. In particular, the use
of the investigational in vitro diagnostic device on individually
identifiable human specimens as described in this rule would not be
human subjects research under 45 CFR part 46, while the analysis of the
individually identifiable data obtained from the use of the
investigational device to determine the safety and effectiveness of the
device would be considered human subject research under 45 CFR part 46.
If the analysis of individually identifiable data involves non-exempt
human subjects research that is conducted or supported by HHS, the
institution conducting the analysis must obtain an OHRP-approved
assurance. In addition, this means that this research activity, if not
exempt, i.e., the analysis of the individually identifiable data, must
be reviewed prospectively by an IRB and must be conducted with the
informed consent of the subjects unless waived. OHRP expects that IRBs
will often find that informed consent may be waived under 45 CFR
46.116(d) for the analysis of the individually identifiable data
obtained through the use of the investigational device. OHRP is issuing
guidance regarding this issue simultaneously with the publication of
this interim final rule which can be found at http://www.hhs.gov/ohrp/policy/index.html. Those interested in seeking additional information
concerning the application of the regulations at 45 CFR part 46 should
contact OHRP. We note that research conducted or supported by another
department or agency may be subject to other laws and regulations.
Sponsors should check to see if they are complying with all applicable
requirements.
V. Legal Authority
FDA believes the statutory authority provided in section
520(g)(3)(D) of the act permits this limited exception to obtaining
informed consent for the use of investigational in vitro diagnostic
devices to identify chemical, biological, radiological, or nuclear
agents in potential terrorism events or other potential public health
emergencies. Section 520(g)(3)(D) of the act specifically states when
an exception from informed consent is permissible. Under section
520(g)(3)(D) of the act, informed consent is required unless the
investigator determines the following in writing: (1) There exists a
life threatening situation involving the human subject of such testing
which necessitates the use of such device; (2) it is not feasible to
obtain informed consent from the subject; and (3) there is not
sufficient time to obtain such consent from the subject's legally
authorized representative. Further, a licensed physician uninvolved in
the testing must agree with this three-part determination in advance of
using the device unless use of the device is required to save the life
of the human subject of such testing, and there is not sufficient time
to obtain such concurrence.
As noted earlier, FDA believes that, if the presence of an agent is
suspected, there exists a life-threatening situation for the subjects
whose specimens have been sent to laboratories. Until the laboratory
identifies the agent to which the subject has been exposed or by which
the subject has been infected, specific treatment cannot be provided.
However, this limited exception applies only if it is also not feasible
to obtain informed consent because there is an inability to
communicate, in a timely manner, with the subject or the subject's
legally authorized representative, and there was no reasonable way to
know, at the time the specimen was collected, that there would be a
need to use the investigational device on that specimen. In such a
situation, the act would permit a limited exception to obtaining
informed consent.
In accordance with section 521 of the act (21 U.S.C. 360k), state
or local requirements that are different from, or in addition to, the
requirements in this rule are expressly preempted. This rule
establishes a new exception from the general requirements for informed
consent, to permit the use of investigational in vitro diagnostic
devices to identify chemical, biological, radiological, or nuclear
agents without informed consent in certain circumstances. Consequently,
State and local laws that require that informed consent be obtained in
those situations are preempted.
VI. Issuance of an Interim Final Rule and Effective Date
FDA is proceeding without notice and comment rulemaking because the
Nation needs to have this regulation in place immediately to be
prepared to deal effectively with a terrorism event or other potential
public health emergency. Under the provisions of the Administrative
Procedure Act at 5 U.S.C. 553(b)(B), FDA finds for good cause that
prior notice and comment on this rule are impracticable and contrary to
the public interest. The absence of this exception was an impediment to
the most efficient and effective public health response to the SARS
outbreak. We do not want the absence of such an exception to be an
impediment to our response to an outbreak of Avian flu or some other
public health emergency. It is critical that FDA act quickly now to
ensure that, in the future, individuals who may have been exposed to a
chemical, biological, radiological, or nuclear agent have the benefit
of the timely use of the most appropriate diagnostic devices, including
those that are investigational. For the same reasons, the agency is
making this interim final rule effective as of the date of publication.
VII. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this interim
final rule 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.
VIII. Analysis of Impacts
FDA has examined the impacts of this interim final rule under
Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 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 rule is consistent with the regulatory philosophy and principles
identified in the Executive order. In addition, the rule is not an
economically significant regulatory action as defined by the Executive
order.
[[Page 32832]]
The Regulatory Flexibility Act requires agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because this interim final rule provides an
exception from an otherwise applicable requirement for investigators,
FDA believes that it does not impose a significant burden. The agency
therefore certifies that this 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 issuing ``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 million or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $115 million, using the most current (2003) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
interim final rule to result in any 1-year expenditure that would meet
or exceed this amount.
IX. Paperwork Reduction Act of 1995
This interim final rule contains information collection provisions
that are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The information collection requirements for this interim final
rule have been approved under the emergency processing provisions of
the PRA. The assigned OMB approval number for this collection of
information is 0910-0586. This approval expires on November 30, 2006.
A description of these provisions is given in the following
paragraphs with an estimate of the annual reporting 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 the following 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
collection of information, including the validity of the 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.
Medical Devices: Informed Consent: Investigational In Vitro Diagnostic
Device To Identify a Chemical, Biological, Radiological, or Nuclear
Threat Agent
Description: This interim final rule amends FDA's informed consent
regulation to provide an exception from the general requirement to
obtain informed consent from the subject of an investigation involving
an unapproved or not cleared in vitro diagnostic device intended to
identify a chemical, biological, radiological, or nuclear agent. For
the exception to apply, it is necessary for the investigator and an
independent licensed physician to make the determination and certify in
writing certain facts concerning the need for use of the
investigational in vitro diagnostic device without informed consent.
The investigator submits this written certification to the IRB. When
reporting the test results to the subject's health care provider and,
possibly, to the appropriate public health authorities, the
investigator must disclose the investigational status of the in vitro
diagnostic device. The investigator must also provide the IRB with the
information required in Sec. 50.25 and the procedures that will be
used to provide this information to each subject or the subject's
legally authorized representative at the time the test results are
provided to the subject's health care provider and possibly to the
public health authorities.
Description of Respondents: Clinical laboratories, physicians.
FDA estimates the burden of the collection of information as
follows:
Table 1.--Estimated Average Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
No. of Annual Frequency Total Annual Hours per
21 CFR Section Respondents per Response Responses Response Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
50.23(e)(1) and (e)(2) 150 3 450 2 900
--------------------------------------------------------------------------------------------------------------------------------------------------------
50.23(e)(4) 150 3 450 1 450
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total Hours 1,350
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.
FDA is adding Sec. 50.23(e)(1) to provide an exception to the
general rule that informed consent is required for the use of an
investigational in vitro diagnostic device for the purpose of preparing
for and responding to a chemical, biological, radiological, or nuclear
terrorism event or other public health emergency, if the investigator
and an independent licensed physician make the determination and later
certify in writing that: (1) There is a life-threatening situation
necessitating the use of the investigational device; (2) obtaining
informed consent from the subject is not feasible because there was no
way to predict the need to use the investigational device when the
specimen was collected, and there is not sufficient time to obtain
consent from the subject or the subject's legally authorized
representative; and (3) no satisfactory alternative device is
available. Under this interim final rule these determinations are made
before the device is used, and the written certifications are made
within 5 working days after the use of the device. If use of the device
is necessary to preserve the life of the subject and there is not
sufficient time to obtain the determination of the independent licensed
physician in advance of using the investigational device, Sec.
50.23(e)(2) provides that the certifications must be made within 5
working days of use of the device. In either case, the certifications
are submitted to the IRB within 5 working days of the use of the
device. From its knowledge of the industry, FDA estimates that there
are approximately 150 laboratories that
[[Page 32833]]
could perform this type of testing. FDA estimates that in the United
States each year there are approximately 450 naturally occurring cases
of diseases or conditions that are identified in CDC's list of category
`A' biological threat agents. The number of cases that would result
from a terrorist event or other public health emergency is uncertain.
Based on its knowledge of similar types of submissions, FDA estimates
that it will take about 2 hours to prepare each certification.
Section 50.23(e)(4) provides that an investigator must disclose the
investigational status of the device and what is known about the
performance characteristics of the device at the time test results are
reported to the subject's health care provider and public health
authorities. Under this interim final rule, the investigator provides
the IRB with the information required by Sec. 50.25 and the procedures
that will be used to provide this information to each subject or the
subject's legally authorized representative. Based on its knowledge of
similar types of submissions, FDA estimates that it will take about 1
hour to prepare this information and submit it to the health care
provider and, where appropriate, to public health authorities.
X. Federalism
FDA has analyzed this interim final rule in accordance with the
principles set forth in Executive Order 13132 on Federalism (64 FR
43255, August 10, 1999). FDA has concluded that the rule raises
federalism implications because, in accordance with section 521 of the
act, this rule preempts State and local laws that require that informed
consent be obtained before an investigational in vitro diagnostic
device may be used to identify a chemical, biological, radiological, or
nuclear agent in suspected terrorism events and other potential public
health emergencies that are different from, or in addition to, the
requirements of this regulation.
In accordance with the Executive order, preemption of State law is
restricted to the minimum level necessary to achieve the objective of
the statute to protect the public health by ensuring that individuals
who may have been exposed to such an agent are able to benefit from the
timely use of the most appropriate diagnostic devices, including those
that are investigational. Also in accordance with the Executive order,
officials at FDA consulted with the States on the effect of this rule
on State law.
The new exception from informed consent is available in a very
narrowly defined set of circumstances. Under these circumstances, a
specimen already would have been taken from the individual. The
individual would not be subjected to any further specimen collection or
other procedure in order for the investigational device to be used on
the specimen. In addition, in the circumstances in which the exception
would apply, it is not only the health of the individual from whom the
specimen was taken that would be at risk. It is possible that other
people, perhaps many other people, would have been exposed to the
chemical, biological, radiological, or nuclear agent as well.
In conclusion, the agency believes that it has complied with all of
the applicable requirements under Executive Order 13132 and has
determined that this final rule is consistent with the Executive order.
XI. Civil Justice Reform
This rule has been reviewed under Executive Order 12988, Civil
Justice Reform. This regulation meets the applicable standards set
forth in sections 3(a) and 3(b)(2) of Executive Order 12988.
XII. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this interim
final rule. Submit a single copy of electronic comments or two paper
copies of any mailed comments, 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.
List of Subjects in 21 CFR Part 50
Human research subjects, Prisoners, Reporting and recordkeeping
requirements, Safety.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
50 is amended as follows:
PART 50--PROTECTION OF HUMAN SUBJECTS
0
1. The authority citation for 21 CFR part 50 continues to read as
follows:
Authority: 21 U.S.C. 321, 343, 346, 346a, 348, 350a, 350b, 352,
353, 355, 360, 360c-360f, 360h-360j, 371, 379e, 381; 42 U.S.C. 216,
241, 262, 263b-263n.
0
2. Section 50.23 is amended by adding paragraph (e) to read as follows:
Sec. 50.23 Exception from general requirements.
(e)(1) Obtaining informed consent for investigational in vitro
diagnostic devices used to identify chemical, biological, radiological,
or nuclear agents will be deemed feasible unless, before use of the
test article, both the investigator (e.g., clinical laboratory director
or other responsible individual) and a physician who is not otherwise
participating in the clinical investigation make the determinations and
later certify in writing all of the following:
(i) The human subject is confronted by a life-threatening situation
necessitating the use of the investigational in vitro diagnostic device
to identify a chemical, biological, radiological, or nuclear agent that
would suggest a terrorism event or other public health emergency.
(ii) Informed consent cannot be obtained from the subject because:
(A) There was no reasonable way for the person directing that the
specimen be collected to know, at the time the specimen was collected,
that there would be a need to use the investigational in vitro
diagnostic device on that subject's specimen; and
(B) Time is not sufficient to obtain consent from the subject
without risking the life of the subject.
(iii) Time is not sufficient to obtain consent from the subject's
legally authorized representative.
(iv) There is no cleared or approved available alternative method
of diagnosis, to identify the chemical, biological, radiological, or
nuclear agent that provides an equal or greater likelihood of saving
the life of the subject.
(2) If use of the investigational device is, in the opinion of the
investigator (e.g., clinical laboratory director or other responsible
person), required to preserve the life of the subject, and time is not
sufficient to obtain the independent determination required in
paragraph (e)(1) of this section in advance of using the
investigational device, the determinations of the investigator shall be
made and, within 5 working days after the use of the device, be
reviewed and evaluated in writing by a physician who is not
participating in the clinical investigation.
(3) The investigator must submit the documentation required in
paragraph (e)(1) or (e)(2) of this section to the IRB within 5 working
days after the use of the device.
(4) An investigator must disclose the investigational status of the
in vitro diagnostic device and what is known
[[Page 32834]]
about the performance characteristics of the device in the report to
the subject's health care provider and in any report to public health
authorities. The investigator must provide the IRB with the information
required in Sec. 50.25 (except for the information described in Sec.
50.25(a)(8)) and the procedures that will be used to provide this
information to each subject or the subject's legally authorized
representative at the time the test results are provided to the
subject's health care provider and public health authorities.
(5) The IRB is responsible for ensuring the adequacy of the
information required in section 50.25 (except for the information
described in Sec. 50.25(a)(8)) and for ensuring that procedures are in
place to provide this information to each subject or the subject's
legally authorized representative.
(6) No State or political subdivision of a State may establish or
continue in effect any law, rule, regulation or other requirement that
informed consent be obtained before an investigational in vitro
diagnostic device may be used to identify chemical, biological,
radiological, or nuclear agent in suspected terrorism events and other
potential public health emergencies that is different from, or in
addition to, the requirements of this regulation.
Dated: May 31, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-8790 Filed 6-6-06; 8:45 am]
BILLING CODE 4160-01-S