[Federal Register Volume 75, Number 33 (Friday, February 19, 2010)]
[Proposed Rules]
[Pages 7412-7426]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-3123]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 16, 58, 71, 101, 170, 171, 190, 312, 511, 571, and 812
[Docket No. FDA-2008-N-0115]
RIN 0910-AC59
Reporting Information Regarding Falsification of Data
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
its regulations to require sponsors to report information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies that involve human subjects or animal subjects conducted by or
on behalf of a sponsor or relied on by a sponsor. A sponsor would be
required to report this information to the appropriate FDA center
promptly, but no later than 45 calendar days after the sponsor becomes
aware of the information. This proposal is necessary because ambiguity
in the current reporting scheme has caused confusion among sponsors.
The proposed rule is intended to help ensure the validity of data that
the agency receives in support of applications and petitions for FDA
product approvals and authorization of certain labeling claims and to
protect research subjects.
DATES: Submit written or electronic comments on this proposed rule by
May 20, 2010. See section V of this document for the proposed effective
date of a final rule based on this document. Submit comments regarding
the information collection by March 22, 2010 to OMB (see ADDRESSES).
[[Page 7413]]
ADDRESSES: You may submit comments, identified by Docket No. FDA-2008-
N-0115 and/RIN number 0910-AC59, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described previously, in
the ADDRESSES portion of this document under Electronic Submissions.
Instructions: All submissions received must include the agency name
and Docket No(s). and Regulatory Information Number (RIN) for this
rulemaking. All comments received will be posted without change to
http://www.regulations.gov, including any personal information
provided. For additional information on submitting comments, see the
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this
document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov and insert the
docket number, found in brackets in the heading of this document, into
the ``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Information Collection Provisions: Submit written comments on the
information collection provisions to the Office of Information and
Regulatory Affairs, Office of Management and Budget (OMB). To ensure
that comments on the information collection are received, please submit
written comments to OMB by FAX to 202-395-7285 or by e-mail to [email protected]. Mark your comments to the attention of the FDA
desk officer and reference this rulemaking.
FOR FURTHER INFORMATION CONTACT:
For information regarding human drugs: Leslie K. Ball, Center for
Drug Evaluation and Research, Office of Compliance, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 5342, Silver
Spring, MD 20993-0002, 301-796-3150, FAX: 301-847-8750.
For information regarding biologics: Steve Ripley, Center for
Biologics Evaluation and Research (HFM-17), Food and Drug
Administration, 5515 Security Lane, rm. 5130, Rockville, MD 20852, 301-
827-6210.
For information regarding medical devices and radiological health:
Michael E. Marcarelli, Center for Devices and Radiological Health, Food
and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 3444,
Silver Spring, MD 20993-0002, 301-796-5490.
For information regarding veterinary medicine: Gail L. Schmerfeld,
Center for Veterinary Medicine (HFV-100), Food and Drug Administration,
7500 Standish Pl., Rockville, MD 20855, 240-276-8300.
For information regarding foods: Linda Katz, Center for Food Safety
and Applied Nutrition (HFS-032), Food and Drug Administration, 5100
Paint Branch Pkwy., College Park, MD 20740, 301-436-1910.
For information regarding good laboratory practices for nonclinical
laboratory studies: Karen Stutsman, Office of Regulatory Affairs (HFC-
230), Food and Drug Administration, 15800 Crabbs Branch Way, Rockville,
MD 20855, 240-632-6847.
For information regarding good clinical practice: Kathleen
Pfaender, Office of Good Clinical Practice (HF-34), 5600 Fishers Lane,
rm. 16-85, Rockville, MD 20857, 301-827-3340.
SUPPLEMENTARY INFORMATION:
I. Introduction
FDA is proposing to require that sponsors\1\ report information
indicating that any person has, or may have, engaged in the
falsification of data in the course of reporting study results, or in
the course of proposing, designing, performing, recording, supervising,
or reviewing studies\2\ that involve human subjects (e.g., clinical
investigations) or animal subjects (e.g., nonclinical laboratory
studies and clinical studies in animals) conducted by or on behalf of a
sponsor or relied on by a sponsor. The sponsor would be required to
report this information to the appropriate FDA center promptly, but no
later than 45 calendar days after the sponsor becomes aware of the
information. The proposed requirement for a sponsor to report
information regarding falsification of data would be ongoing and cover
the periods before and after study completion, including after the
review, approval, or authorization of the affected product or labeling.
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\1\ FDA regulations on food additive, color additive, health
claim, and nutrient content claim petitions refer to petitioners,
rather than sponsors. In addition, the FDA regulation for the
submission of new dietary ingredient notifications refers to a
manufacturer or distributor, and the FDA regulation for the
submission of a food contact notification (FCN) refers to a
manufacturer or supplier, rather than sponsor. For the sake of
brevity, FDA is using the term ``sponsor'' in this document to refer
to petitioners submitting food additive, color additive, nutrient
content claim, and health claim petitions; manufacturers or
distributors submitting new dietary ingredient notifications; and
sponsors as defined in Sec. Sec. 58.3(f), 312.3(b), 510.3(k), and
812.3(n) (21 CFR 58.3(f), 312.3(b), 510.3(k), and 812.3(n)). The
term ``sponsor'' as used in this document does not include a Federal
agency that sponsors research or investigations through funding or
contracts or an entity identified as a ``sponsor'' under other
Federal programs (e.g., a recipient of funding from the National
Institutes of Health), except to the extent that any such Federal
agency or entity is a petitioner, manufacturer, distributor, or
sponsor as specified in the preceding sentence.
\2\Henceforth, the term ``studies'' means studies involving
human subjects (e.g., clinical investigations) or animal subjects
(e.g., nonclinical laboratory studies and clinical studies in
animals).
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We are proposing to amend the appropriate regulations that govern
the conduct of FDA-regulated research and the submission of information
in support of applications and petitions for FDA product approvals and
authorization of certain labeling claims. This requirement would be
added to FDA's regulations on:
Good laboratory practice for nonclinical laboratory
studies (21 CFR part 58),
Color additive petitions in part 71 (21 CFR part 71),
Petitions for nutrient content claims and petitions for
health claims in part 101 (21 CFR part 101),
Information in a premarket notification for a food contact
substance (FCN) in part 170 (21 CFR part 170),
Food additive petitions (21 CFR part 171),
Dietary supplements (21 CFR part 190),
Investigational new drug applications (21 CFR part 312),
New animal drugs for investigational use (21 CFR part
511),
Food additive petitions (21 CFR part 571), and
Investigational device exemptions (21 CFR part 812).
[[Page 7414]]
A. Background
Falsification of data can, if not detected, undermine subject
protection and the underlying basis for FDA actions. Each year, FDA
discovers falsification of data at study sites and in application
submissions. Sometimes, falsification at a study site is not an
isolated event and can lead to a finding of falsification of
information at another site, or relating to other drugs being studied
at the same site. It is critical that participants in the product
development process assist FDA in detecting falsification of data.
FDA's proposal to amend the regulations has its origins in events
that occurred in the mid- to late-1990s, when complaints to FDA and
followup through FDA's bioresearch monitoring program revealed some
particularly egregious cases of falsification of data by clinical
investigators. For example, in one case, an investigator falsified data
that extended across studies in 91 applications submitted to FDA by 47
different sponsors.
After discovering this widespread falsification, FDA attempted to
determine why so widespread a practice remained unreported to FDA. In a
series of FDA meetings, as well as congressional briefings, FDA
reviewed the current requirements for sponsor reporting of noncompliant
investigators, reviewed study monitoring procedures, and listened to
the views of an industry trade association. In addition, the Center for
Drug Evaluation and Research (CDER) established an internal working
group to evaluate the effectiveness of the current reporting
requirements for sponsors. The working group identified several areas
of ambiguity in the current regulations related to: (1) The extent to
which possible falsification of data had to be reported to the agency;
(2) the amount and type of information that sponsors must report when a
study and/or an investigator's participation in a study has terminated;
(3) whose falsification of data must be reported; and (4) the timing of
reporting.
B. Why FDA Is Proposing This Rule
We are proposing this rule for two principal reasons. First, it is
important for the agency to have confidence in any data from studies
conducted by, or on behalf of, a sponsor, or relied on by a sponsor for
product approvals or authorization of labeling claims. This proposed
rule is intended to help ensure the integrity of data submitted to FDA
because reliance on falsified data could lead to clinical testing of
unsafe products, approval of ineffective or unsafe products, or
marketing of products with false or misleading claims. Second, it is
important that the rights, safety, and welfare of subjects be
protected. This proposed rule is intended to help protect research
subjects\3\ by making it less likely that persons who falsify data will
continue to conduct studies, come in contact with research subjects, or
jeopardize the rights, safety, and welfare of such subjects through
unsound scientific practices.
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\3\ For the sake of brevity, FDA is using the term ``subjects''
to refer to human and animal subjects.
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Although our own inspections sometimes uncover falsification of
data, sponsors of studies are responsible for ensuring the integrity of
study data and are in a better position to discover possible
falsification of data through their monitoring, auditing, and reviewing
of data. We understand that in the process of reviewing and monitoring
studies, some sponsors have discovered falsification of data and have
been reluctant, or uncertain as to whether it was necessary, to report
the information to us. For example, we are aware that in some cases,
sponsors, believing that an investigator may have falsified data, have
decided to retain the investigator but exclude the investigator's data
without specifying the reason. In other cases, sponsors have terminated
the investigator's participation in the study without notifying us of
the specific reason. We are concerned that when these situations occur,
an investigator who may have falsified data might continue to conduct
studies, thereby jeopardizing the rights, safety, and welfare of the
subjects involved in future research and the integrity of data in other
studies.
Therefore, the agency is proposing this rule to clarify sponsors'
reporting requirements for studies conducted by, or on behalf of, a
sponsor or on which a sponsor relies to support product approvals, new
dietary ingredient notifications, or authorization of labeling claims,
including nutrient content claims and health claims. This proposed rule
makes it clear that sponsors would be required to promptly report
information indicating that any person has, or may have, engaged in the
falsification of data in the course of reporting study results, or in
the course of proposing, designing, performing, recording, supervising,
or reviewing studies conducted by, or on behalf of, a sponsor or relied
on by a sponsor. This proposed rule, when finalized, would require
sponsors to report information to the appropriate FDA center about
possible falsification of data whenever (before, during, or after the
completion of a study) a sponsor becomes aware of the information, but
in no case later than 45 calendar days after the sponsor becomes aware
of that information.
The proposed regulation would allow the agency to more rapidly
identify persons who have falsified data and more effectively address
problems. Such persons may include those who have falsified data
submitted to FDA for product reviews, approvals, and authorizations of
certain labeling claims, in addition to those who have falsified data
in the course of conducting FDA-regulated research. We intend to use
the information collected from sponsors who notify us of possible
falsification of data to identify patterns, potential signals, or other
indications of misconduct, so that we can conduct further
investigations. These investigations, in turn, may form the basis of
administrative or enforcement actions, such as excluding clinical
trials from consideration by FDA, placing a clinical trial on hold, or
initiating disqualification of investigators or criminal proceedings.
Taking effective action in response to falsification could lessen the
magnitude and impact of the falsification in a current study, reduce
the potential for delays or compromise to other studies and
applications (including studies and applications from other sponsors
for whom such a person might also be working), and protect the rights,
safety, and welfare of research subjects.
II. Description of the Proposed Rule
A. What Changes Are We Proposing to Make?
Under proposed Sec. Sec. 58.11(a), 71.1(k), 101.69(p), 101.70(k),
170.101(f), 171.1(o), 190.6(g), 312.56(e), 511.1(c), 571.1(l), and
812.46(d), sponsors would be required to report to the appropriate FDA
center information indicating that any person has, or may have, engaged
in the falsification of data in the course of reporting study results,
or in the course of proposing, designing, performing, recording,
supervising, or reviewing studies conducted by or on behalf of a
sponsor or relied on by a sponsor. For the purposes of this proposed
rule, ``falsification of data'' means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. These reporting requirements would apply to
information related to studies including, but not limited to, clinical
investigations, nonclinical laboratory studies, and clinical studies in
animals.
FDA does not intend to impose any additional monitoring
responsibilities under this proposed rule. This proposal
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does not relieve sponsors of any other applicable statutory or
regulatory requirements.
B. Who Would Be Required to Report Information to FDA?
The proposed rule would require sponsors, as defined earlier in
this preamble, to report certain information related to confirmed or
possible falsification of data.
C. Whose Falsification of Data Would a Sponsor Be Required to Report?
FDA is seeking information on falsification of data by any person
involved in studies conducted by or on behalf of a sponsor or relied on
by a sponsor. In FDA's experience, falsification may be committed by
individuals responsible for conducting studies and/or by their
colleagues or subordinates. FDA believes that all persons involved in
such actions must be identified so that future falsification of data
can be prevented. Therefore, FDA is proposing in this regulation to
require sponsors to inform FDA of any confirmed or possible
falsification of data by any person involved in studies conducted by or
on behalf of a sponsor or relied on by a sponsor.
D. Can FDA Provide Any Examples of Falsification of Data That Would Be
Subject to the Reporting Requirements of This Proposed Rule?
``Falsification of data'' is defined for the purpose of this
proposed rule as creating, altering, recording, or omitting data in
such a way that the data do not represent what actually occurred.
Instances of falsification of data may fall into one or several of
these categories. The following, although not comprehensive, represent
examples of falsification of data that would be reportable under this
proposed rule:
Creating data that were never obtained (e.g., making up
data or results and recording or reporting them; reporting enrollment
in a study of a subject who did not exist; forging the signature on an
informed consent form)
Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal)
Recording or obtaining data from a specimen, sample, or
test whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject)
Omitting data that were obtained and would be appropriate
for recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed)
Although the examples above are each characterized as a particular
type of falsification of data, we recognize that even these examples
can fall into one or more categories. Because instances of
falsification of data might fall into one or more of these categories,
sponsors would not need to specifically characterize the falsification
(e.g., creating, recording, altering, or omitting data) in the reports
they would be required to submit to us.
E. Would Sponsors Be Required to Report Errors Under This Proposed
Rule?
Errors, which can include, as noted in the proposed codified
language, typographical errors and transposed numbers or characters,
should not be reported under this proposed rule. The proposed rule is
designed to address falsification of data rather than unintentional
errors in recording and reporting information for several reasons:
Falsification is more difficult for FDA to detect than
errors during the normal inspectional process, in part because persons
who engage in falsification are more likely to attempt to conceal their
actions.
Persons who engage in falsification of data often repeat
that conduct when they are participating in multiple studies that
affect multiple sponsors, so the impact of the conduct is often greater
than that for errors.
Although significant errors could potentially compromise
the integrity of data submitted to FDA, it is more likely that these
errors will be addressed through FDA inspections, sponsor monitoring
activities, and the agency's application review processes than is the
case with falsification of data.
Requiring sponsors to report every observed error in data
recording and processing could overwhelm the agency with information,
much of which would already be detected through the activities noted
above and would ultimately be of little concern with respect to the
safety or effectiveness of regulated products.
For these reasons, at this time we are proposing to exclude errors
from the proposed reporting requirement to best utilize the agency's
resources.
We also are soliciting comments on whether we should include
additional descriptions of what we consider ``errors'' and, if so, what
would be specific examples of such errors.
F. Would a Sponsor Be Required to Report Possible Falsification?
The proposed codified language includes the phrase ``has, or may
have, engaged in the falsification of data'' to make clear that the
sponsor is required to report not only confirmed, but also possible,
falsification. It is not always possible for an observer to know the
intent of a person who may have falsified data. The proposed rule would
not require a sponsor to determine definitively that data have been
falsified, nor would the proposed rule require that a sponsor determine
the intent of the person who has, or may have, falsified data. Rather,
a sponsor would be required to report information of which it is aware
suggesting that a person has, or may have, engaged in the falsification
of data in connection with studies conducted by, or on behalf of, the
sponsor, or relied on by the sponsor. This reporting obligation would
exist regardless of the amount of evidence, if any, the sponsor has
with regard to the intent of the person who has, or may have, falsified
data.
We purposely are not proposing to specify in the regulations any
particular information threshold that must be met before the reporting
requirements are triggered, such as the exact form, quantity, or
reliability of information about possible falsification that would
require a sponsor to report to FDA. We do not believe that it is
feasible to codify all forms of information on possible falsification
(e.g., discovery of possibly altered document, report by coworker,
complaint by study subject) or specify a quantity of information that
would constitute a minimum threshold for sponsor reporting, and we do
not want to inadvertently exclude information that, upon further
investigation by the agency, could help uncover falsification. However,
we invite comment on whether the regulation should specify some form of
evidentiary standard or minimum threshold, such as what form(s) or
quantity of information is needed to create a requirement to report
and, if so, what the standard should be (see also section IX of this
document).
G. How Will FDA Use This Information?
FDA would determine whether further agency investigation is
warranted based on the information reported under this proposed rule in
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conjunction with other information available to us. These
investigations, in turn, might form the basis of administrative or
enforcement actions, such as excluding clinical trials from
consideration by FDA, placing a clinical trial on hold, or initiating
disqualification of investigators or criminal proceedings.
Although a single sponsor may have only a small amount of
information about a particular person or incident, the reporting that
would be required by this proposed rule, independently or when
aggregated with reports from other sources, may provide sufficient
information from multiple sources about a person or situation to
indicate that FDA should conduct an investigation. FDA would determine
whether further agency investigation is warranted based on the
information reported under this proposed rule in conjunction with other
information available to FDA. Sponsors should therefore not wait to
determine conclusively whether falsification actually occurred, or seek
to determine the circumstances that led to it, before reporting this
information to FDA.
The intent of this proposed requirement is for FDA to obtain
information about possible falsification as soon as possible, with the
full recognition that further investigation may be needed to
substantiate allegations of possible falsification before any
administrative or enforcement actions are taken. The act of being
reported to FDA for possible data falsification would not necessarily
mean that falsification had occurred or that the agency would make such
a determination. The information likely would be assessed in light of
the existing legal and regulatory framework and, as appropriate, would
be considered in the context of administrative or enforcement
proceedings. Persons suspected of data falsification would be entitled
to the legal and procedural rights that would typically apply in any
such administrative or enforcement proceedings.
Early reporting by sponsors could alert FDA to conditions that may
affect data integrity and the rights, safety, and welfare of subjects.
This reporting requirement would have the effect of providing FDA with
an early alert to potentially serious lapses in subject protection or
data integrity. If FDA were made aware of possible falsification of
data sooner, FDA could undertake appropriate action, such as reviewing
other studies conducted by the persons who have, or may have, falsified
data to assess the reliability of the data and/or conducting site
inspections.
H. What Information Should Sponsors Include in the Required Report to
FDA?
The proposed rule would require the sponsor to report to FDA
information it possesses regarding the possible falsification of data.
The information a sponsor should report to FDA includes the following:
The name of the person who has, or may have, falsified
data;
The last known address(es) and phone number(s) of that
person;
The specific identity of the potentially affected study,
including, when applicable, application information such as the
application number, investigational protocol number, study title, study
site(s), and study dates; and
Information suggesting that falsification occurred and
describing the falsification. A sponsor may provide this information by
any means, including telephone, mail, electronic mail, or facsimile.
We are considering whether additional information should be
included in the report to FDA. One such element could be the National
Clinical Trial (NCT) number assigned to a study when an applicable
clinical trial is registered with ClinicalTrials.gov. We also are
considering whether the regulations should specify what information
about possible falsification must be reported to FDA.
Although the proposal would require only sponsors to report
information about possible falsification of data, FDA also encourages
other persons to report such information. FDA reminds sponsor-
investigators that they would be responsible for reporting
falsification of data under this proposed rule because they must adhere
to the requirements applicable to both sponsors and investigators.
I. How Does a Sponsor Become Aware of Data Falsification?
There are many ways a sponsor can become aware of possible
falsification, including, but not limited to, monitoring the conduct of
studies, reviewing and evaluating study data (e.g., noticing unusual
data in case report forms and/or analytical reports), and receiving
complaints from employees or former employees.
J. When Would a Sponsor Be Required to Report Information About
Falsification of Data?
The agency is proposing to require sponsors to report information
regarding falsification of data ``promptly,'' but no later than 45
calendar days after the sponsor becomes aware of the information. It is
important for FDA to receive information about the falsification of
data in a timely manner to ensure protection of the integrity of data
reviewed by the agency and protection of subjects. We believe that 45
calendar days would provide a sponsor a reasonable amount of time to
review the information and report any actual or suspected falsification
to FDA. The proposed requirement for a sponsor to report information
regarding falsification of data would be ongoing and cover the periods
before and after study completion, including after the review,
approval, or authorization of the affected product or labeling.
K. What Are the Consequences of Not Reporting Confirmed or Possible
Falsification?
Failure to report possible falsification of data might constitute a
violation of section 301(e) of the Federal Food, Drug, and Cosmetic Act
(the act) (21 U.S.C. 331(e)) (concerning failure to make a required
report) or 18 U.S.C. 1001 (concerning the submission of a false
statement to the Federal government).
L. Whom Would a Sponsor Inform About Falsification?
As proposed, a sponsor would be required to report information it
discovered regarding falsification of data to the appropriate FDA
center. For investigations involving a combination product, the sponsor
should report information on falsification to the FDA center that has
primary jurisdiction for the premarket review and regulation of the
product.
Current contact information for each center is listed below as
follows:
Center for Biologics Evaluation and Research (CBER): Office of
Compliance and Biologics Quality (HFM-650), Division of Inspections and
Surveillance, Center for Biologics Evaluation and Research, FDA, 1401
Rockville Pike, rm. 200N, Rockville, MD 20852-1448, 301-827-6221, FAX
301-827-6748.
Center for Devices and Radiological Health (CDRH): Office of
Compliance, Division of Bioresearch Monitoring (HFZ-310), Center for
Devices and Radiological Health, FDA, 10903 New Hampshire Ave., Bldg.
66, rm. 3444, Silver Spring, MD 20993-0002, 301-796-5490, FAX 301-847-
8136.
Center for Drug Evaluation and Research (CDER): Division of
Scientific Investigations, Office of Compliance, Center for Drug
Evaluation and Research, FDA, 10903 New Hampshire Ave., Bldg. 51, rm.
5311, Silver Spring, MD 20993-0002, 301-796-3150, FAX 301-847-8748.
[[Page 7417]]
Center for Food Safety and Applied Nutrition (CFSAN): Office of
Compliance, Division of Enforcement (HFS-605), Center for Food Safety
and Applied Nutrition, FDA, 5100 Paint Branch Pkwy., College Park, MD
20740-3835, 301-436-2417, FAX 301-436-2656.
Center for Veterinary Medicine (CVM): Office of Surveillance and
Compliance, Division of Compliance (HFV-230), Center for Veterinary
Medicine, FDA, 7500 Standish Pl., Rockville, MD 20850, 240-276-9200,
FAX 240-276-9241.
Office of Regulatory Affairs (ORA): Office of Enforcement (HFC-
230), FDA, 15800 Crabbs Branch Way, Rockville, MD 20855, 240-632-6853.
M. What Is the Proposed Definition of ``Data'' for the Purposes of This
Proposal?
In this proposal, the term ``data'' includes, but is not limited
to, individual facts, tests, specimens, samples, results, statistics,
items of information, or statements made by individuals. This proposed
rule would apply to data from studies conducted by or on behalf of a
sponsor or relied on by a sponsor. Thus, it would apply not only to
data from studies conducted by a sponsor, but also to data from studies
not sponsored or conducted by a sponsor but cited in a petition, new
dietary ingredient notification, or application to FDA in support of a
claim, product marketing, or other regulatory action such as
reclassification of a device.
N. Why Does FDA Want to Issue This Proposal Given Existing Regulations
on Research Misconduct?
The Public Health Service (PHS) regulations at 42 CFR part 93 and
the National Science Foundation (NSF) regulations at 45 CFR part 689
address ``research misconduct.'' The PHS research misconduct
regulations generally apply to PHS-conducted or PHS-supported
biomedical and behavioral research, research training, research-related
activities, and applications and proposals for such PHS-supported
research, research training, and related activities. The NSF
regulations on research misconduct address research proposals submitted
to NSF and funded by NSF. As a result, neither of these regulations
encompasses sufficiently the scope of research subject to evaluation by
FDA.\4\ FDA's proposed rule is intended to cover all studies that are
subject to FDA evaluation, regardless of the source of funding.
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\4\ References made in this proposed rule to ``research'' and
``studies'' that are ``subject to evaluation by FDA'' include
research and studies that are otherwise within the scope of the
codified provisions in this proposed rule.
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Furthermore, FDA is not adopting any definition of ``research
misconduct'' for the purpose of this proposal for two additional
reasons. First, FDA's proposed definition of ``falsification of data``
describes the kinds of falsification of data that the agency has
actually encountered that can affect both application reviews and the
safety of subjects. Second, the PHS and NSF research misconduct
regulations include the category ``plagiarism'' in the definitions of
``research misconduct.'' Although plagiarism is an important issue in
the context of Federal research grants and contracts, it is an area
generally outside the scope of FDA compliance oversight. Accordingly,
FDA is proposing to not include plagiarism in the category of activity
that would trigger reporting under the proposed rule.
O. Why Is FDA Proposing to Change the Section Heading of Sec. 312.56?
FDA is proposing to change the section heading of Sec. 312.56 from
``Review of ongoing investigations'' to ``Review of ongoing
investigations; reporting falsification of data'' to reflect the
addition of this proposed reporting requirement to this section.
P. Why Is FDA Proposing to Renumber Sec. 58.217 to Sec. 58.12?
FDA is proposing to renumber Sec. 58.217 to Sec. 58.12 to place
sponsor responsibilities under the regulations in consecutive sections.
The proposed revisions to the language in current Sec. 58.217 include
changing the first sentence to read ``subpart K of this part'' instead
of ``this subpart'' and several minor plain language edits.
Q. Why Is FDA Not Proposing to Amend Parts 314, 514, 601, and 814?
We recognize that the applicant (under 21 CFR parts 314, 514, 601,
807, and 814) is not always the sponsor for a given study and that
arrangements between sponsors and applicants can sometimes be complex.
We currently believe that sponsors are in the best position to detect
and report falsification of data as described in this proposal.
However, this proposal does not relieve applicants of any
responsibilities under applicable statutes and regulations (e.g., parts
314, 514, 601, 807, and 814). It may be appropriate to extend the
reporting requirements described in this proposed rule to nonsponsor
applicants if we have reason to believe that they are also in a
position to discover falsification of data described in this proposed
rule and that existing statutes and regulations are not adequate to
capture this information. Therefore, we request comment on whether we
should require nonsponsor applicants to comply with the requirements in
the proposed rule and whether such applicants are in a position to
discover falsification of data.
III. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
IV. Legal Authority
FDA is proposing this rule under the authority granted to it by the
act (21 U.S.C. 301 et seq.) and the Public Health Service Act (PHS Act)
(42 U.S.C. 201 et seq.). By delegation from the Secretary of the
Department of Health and Human Services (the Secretary), FDA is
authorized to issue regulations for the efficient enforcement of the
act (21 U.S.C. 371). Any final rule upon which this proposal is based
would help with the efficient enforcement of provisions relating to the
following: (1) Investigational use of human drugs, animal drugs,
biologics, and devices; (2) investigational and approved use of food
additives and color additives; (3) safety and, as appropriate,
effectiveness of human and animal drugs, biological products, and
medical devices; (4) accuracy of a health claim or nutrient content
claim in food labeling; and (5) establishing that a new dietary
ingredient will reasonably be expected to be safe.
FDA may require the establishment and maintenance of such records,
and the making of such reports to FDA, of data obtained as a result of
the investigational use of an animal drug (21 U.S.C. 360b(j)), a
biologic (42 U.S.C. 262(a)(3)), a device (21 U.S.C. 360j(g)(2)(B)(ii)),
a human drug (21 U.S.C. 355(i)), a food additive (21 U.S.C. 348(b),
(j), and (h)), or a color additive (21 U.S.C. 379e(b)). FDA may require
the submission of balanced information, which is necessary for FDA to
evaluate: The safety of a food additive (21 U.S.C. 348), the safety and
suitability of a color additive (21 U.S.C. 379e), the accuracy of a
health claim or nutrient content claim in food labeling (21 U.S.C.
343(r)(2)(A), (r)(3)(B)), and the basis on which a manufacturer or
distributor concluded that a new dietary ingredient will reasonably be
expected to be safe
[[Page 7418]]
(21 U.S.C. 350b(a)(2)). FDA may also require the establishment and
maintenance of such records, and the making of such reports to FDA, as
are necessary to determine whether there are, or may be, grounds to
withdraw the approval or authorization of an animal drug (21 U.S.C.
360b(l)), a biologic (42 U.S.C. 262(a)(2)(A)), a device (21 U.S.C.
360i), a human drug (21 U.S.C. 355(k)), a food additive (21 U.S.C.
348), a color additive (21 U.S.C. 379e), a health claim (21 U.S.C.
343(r)(2)(A)), or a nutrient content claim (21 U.S.C. 343(r)(2)(B)), or
when reasonably necessary to determine that a dietary supplement
containing a new dietary ingredient may no longer meet the provisions
in 21 U.S.C. 350b(a)(2).
Moreover, other provisions, such as 21 U.S.C. 355(i), 42 U.S.C.
262, and 21 U.S.C. 360b(j) and 360j(g)(2), confer broad authority upon
the Secretary (and, by delegation, to FDA) to issue regulations
governing the investigational use of new drugs, biologics, new animal
drugs, and devices to protect the rights, safety, and welfare of
subjects and otherwise protect the public health. Other provisions,
such as 21 U.S.C. 355(b) to (d), 360b(b) to (d), 360e(2)(A), and
360e(c)(1), give the agency the authority to obtain the information we
need to adequately assess the safety and effectiveness of drugs and
devices. In determining whether a drug or device is ``safe for use''
under the conditions proposed, the agency may consider not only
information such as data from studies, but also ``any other
information'' or ``new information'' before the agency relevant to the
approval decisions under 21 U.S.C. 355(d), 360b(d), and 360e(d)(2). The
language in 21 U.S.C. 355(d), 360b(d), and 360e(c)(1) is intended to
help ensure that consumers are not exposed to products for which safety
and effectiveness have not been demonstrated.
Similarly, 21 U.S.C. 360e gives the agency the authority to obtain
the information we need to determine whether a premarket approval
application provides reasonable assurances of the safety and
effectiveness of a device. Under 21 U.S.C. 360c(i), persons submitting
premarket notifications are required to submit a summary of any
information respecting safety and effectiveness or state that such
information will be made available upon request.
In addition, under 21 U.S.C. 355(e), 360b(e)(1), and 360e(e)(1),
approval of an application is to be withdrawn if, inter alia, new
information shows that the drug or device is unsafe or has not been
shown to be either safe or effective under the conditions of use.
As discussed previously, the proposal, when final, would help
efficiently enforce provisions relating to: (1) The safety and, as
appropriate, effectiveness of human and animal drugs, biological
products, and medical devices; (2) the safety of food additives and new
dietary ingredients; (3) the safety and suitability of color additives;
and (4) the accuracy of nutrient content claims and health claims. FDA
believes the proposal would help prevent the use of falsified data in
evaluating the safety and, as appropriate, suitability, accuracy, or
effectiveness of such products. The proposed changes would also help to
protect research subjects.
Provisions for misbranding (21 U.S.C. 352 and 343) and adulteration
(21 U.S.C. 351 and 342) also provide authority for issuance of these
regulations.
V. Proposed Implementation Plan
FDA proposes that any final rule that may issue based on this
proposal become effective 90 days after the date of publication in the
Federal Register.
VI. Analysis of Impacts
FDA has examined the impacts of the proposed 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 proposed rule is not an economically 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 the
rule on small entities. Because most firms would not generally submit
more than one report of potential data falsification per year at the
estimated cost of only $210 per report, the agency does not believe
that this proposed rule would 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 $133 million, using the most current (2008) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
proposed rule to result in any 1-year expenditure that would meet or
exceed this amount.
The proposed rule would amend FDA's regulations to require sponsors
to report information indicating that any person has, or may have,
falsified data in the course of reporting study results, or in the
course of proposing, designing, performing, recording, supervising, or
reviewing studies conducted by or on behalf of a sponsor or relied on
by a sponsor. For the purpose of this proposal, ``falsification of
data'' means creating, altering, recording, or omitting data in such a
way that the data do not represent what actually occurred. Sponsors
would be required to report this information to the appropriate FDA
center promptly, but no later than 45 calendar days after the sponsor
becomes aware of the information.
A. Benefits
The benefits of the changes being proposed would be the decreased
likelihood that FDA would rely on falsified data for product reviews
and approvals, or for authorization of certain labeling claims. The
proposed changes would also decrease the likelihood of harm to research
subjects by making it less likely that clinical studies would begin or
continue if falsified data from nonclinical laboratory studies were
reported. The proposed changes would also prevent researchers who
falsify data from continuing studies, coming in contact with research
subjects, or jeopardizing the safety of such subjects through unsound
scientific practices.
B. Costs
Regulatory costs will reflect the added paperwork cost of
submitting the information reports. Given the great flexibility
provided in the manner in which the reports can be made, FDA believes
that they will be simple to complete. Therefore, FDA estimates that it
will take about 5 hours to prepare and report this information to the
agency. The agency is uncertain of the average number of these reports
to expect annually. As explained in section VII of this document, the
agency estimates that it may receive 73 reports per year in compliance
with this rule (see Table 1.--Estimated Annual Reporting
[[Page 7419]]
Burden). FDA is basing this estimate on several types of information,
including reports received from sponsors of errors and reports of
suspensions and terminations of clinical investigators. Because most
errors do not involve falsification and because investigators may be
suspended or terminated for reasons other than for falsifying data,
this estimate of 73 reports is likely to be greater than the number the
agency would actually receive. At a benefit-adjusted hourly wage rate
of about $42 for a regulatory affairs official, these assumptions imply
a total annual cost of about $15,330 per year.\5\ As mentioned
previously, the agency expects the total number of reports of falsified
data, and therefore the total cost, to be lower. Although a small
number of firms may submit more than one report in a year, most firms
would not generally submit more than one report per year. At an
estimated cost of only about $210 per report, the agency concludes that
the proposed rule would not have a significant economic impact on a
substantial number of small entities. The Unfunded Mandates Reform Act
of 1995 does not require FDA to prepare a statement of costs and
benefits for the proposed rule, because the proposed rule is not
expected to result in any 1-year expenditure that would meet or exceed
$100 million adjusted for inflation. The current inflation-adjusted
statutory threshold is $133 million.
---------------------------------------------------------------------------
\5\ 2004 National Industry-Specific Occupational Employment and
Wage Estimates, US Department of Labor, Bureau of Labor Statistics
(www.bls.gov/oes/current/naics4_325400.htm); compliance officer
wage rate for pharmaceutical and medicine manufacturing (NAICS
325400) plus a 30-percent increase for benefits.
---------------------------------------------------------------------------
VII. Paperwork Reduction Act of 1995
This proposed 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 (44 U.S.C. 3501-3520) (the
PRA). Collections of information include any request or requirement
that persons obtain, maintain, retain, or report information to the
agency, or disclose information to a third party or to the public (44
U.S.C. 3502(3) and 5 CFR 1320.3(c)). A description of the information
collection requirements included in this proposed rule is given below
with an estimate of the annual reporting burden. Included in this
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: (1) Whether the proposed collection of
information is necessary for the proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Title: Reporting Information Regarding Falsification of Data.
Description: FDA is proposing to amend its regulations on review of
studies to require sponsors to report information indicating that any
person has, or may have, engaged in the falsification of data in the
course of reporting study results, or in the course of proposing,
designing, performing, recording, supervising, or reviewing studies
conducted by or on behalf of a sponsor or relied on by a sponsor. The
sponsor would be required to report this information to the appropriate
FDA center promptly, but no later than 45 calendar days after the
sponsor becomes aware of the information. For the purpose of this
proposal, ``falsification of data'' means creating, altering,
recording, or omitting data in such a way that the data do not
represent what actually occurred.
FDA believes that this proposal is necessary because ambiguity in
the current regulations has caused considerable confusion among
sponsors. FDA intends to make it absolutely clear that sponsors would
be required to report information pertaining to the possible
falsification of data as described in this proposal. This proposal is
intended to help ensure the integrity of data received by FDA in
support of applications and petitions for product approval and
authorization of certain labeling claims and to help protect research
subjects. In addition, this proposal would protect research subjects by
making it less likely that falsified nonclinical laboratory studies
would be relied on by the agency and that researchers who falsify data
could continue to conduct studies, come in contact with research
subjects, and/or jeopardize the rights, safety, and welfare of such
subjects through unsound scientific practices.
Based on data concerning the number of reports of falsification
received annually by FDA, FDA estimates that it will receive
approximately 73 reports of falsification of data per year. FDA bases
this estimate on the fact that CDER receives approximately 20 reports a
year from sponsors, CBER receives approximately 30 per year, and CDRH
receives approximately 15. There are approximately three incidents a
year concerning nonclinical laboratory studies. CFSAN receives
approximately three reports a year concerning food additive petitions
and color additive petitions. CFSAN has received no reports concerning
nutrient content claims, health claims, or new dietary ingredients. CVM
receives approximately two reports a year.
FDA estimates that it will take approximately 5 hours to prepare
and submit to FDA each report. FDA bases this estimate on the time it
would take a sponsor to gather the information to report to FDA,
contact FDA to report the information, and meet with FDA to present the
report, if necessary.
The reporting burden posed by the proposed rule is considerably
less than the burden posed by the PHS research misconduct regulations,
primarily because the proposed rule would require fewer specific
actions by sponsors. The PRA section of the final rule on the PHS
research misconduct regulations (70 FR 28370, 28382 to 28384; May 17,
2005) describes the extensive efforts that a research institution must
undertake to investigate and document research misconduct, including
promptly taking custody of all records and evidence, performing an
inventory of these items, and sequestering them, as well as taking
custody of additional records and evidence discovered during the course
of a research misconduct proceeding. FDA's proposed rule on
falsification would not require extensive investigation, documentation,
and recordkeeping, but rather would simply require reporting of known
or potential data falsification when a sponsor becomes aware of
information indicating that such activity may have occurred. This would
impose a substantially lesser burden than that created by the PHS rule.
Description of Respondents: Persons and businesses, including small
businesses and manufacturers.
[[Page 7420]]
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
--------------------------------------------------------------------------------------------------------------------------------------------------------
58.11(a) 3 1 3 5 15
--------------------------------------------------------------------------------------------------------------------------------------------------------
71.1(k) 1 1 1 5 5
--------------------------------------------------------------------------------------------------------------------------------------------------------
101.69(p) 0 0 0 0 0
--------------------------------------------------------------------------------------------------------------------------------------------------------
101.70(k) 0 0 0 0 0
--------------------------------------------------------------------------------------------------------------------------------------------------------
170.101(f) 1 1 1 5 5
--------------------------------------------------------------------------------------------------------------------------------------------------------
171.1(o) 1 1 1 5 5
--------------------------------------------------------------------------------------------------------------------------------------------------------
190.6(g) 0 0 0 0 0
--------------------------------------------------------------------------------------------------------------------------------------------------------
312.56(e) 50 1 50 5 250
--------------------------------------------------------------------------------------------------------------------------------------------------------
511.1(c)(1) 2 1 2 5 10
--------------------------------------------------------------------------------------------------------------------------------------------------------
571.1(l) 0 0 0 0 0
--------------------------------------------------------------------------------------------------------------------------------------------------------
812.46(d) 15 1 15 5 75
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total 73 7 73 35 365
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3507(d)), the agency has submitted the information collection
provisions of this proposed rule to OMB for review. Interested persons
are requested to send comments regarding this information collection to
the Office of Information and Regulatory Affairs, OMB (see ADDRESSES).
Before this proposed rule becomes final, FDA will publish a notice
in the Federal Register announcing OMB's decision to approve, modify,
or disapprove the information collection provisions in the final rule.
An agency may not conduct or sponsor, and a person is not required to
respond to, a collection of information unless the information
collection displays a current OMB control number.
VIII. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
the agency has concluded that the proposed rule does not contain
policies that have federalism implications as defined in the Executive
order and, consequently, a federalism summary impact statement is not
required.
IX. Request for Comments
In addition to requesting general comments on the proposed rule,
FDA has also identified several specific issues on which it invites
public comment. The public comments will help FDA decide whether
additional revisions to the proposed regulations are needed. The issues
are as follows:
(1) We welcome comments concerning the definition of
``falsification of data.''
(2) The proposed rule states that the information should be
reported to FDA ``promptly,'' but no later than 45 calendar days after
the sponsor becomes aware of the information. We believe that 45
calendar days would provide a sponsor a reasonable amount of time to
review the information to determine if it must be reported to FDA.
However, we welcome comments on whether this timeframe is appropriate.
(3) Although we have not proposed to amend regulations related to
marketing applications (i.e., parts 314, 514, 807, and 814), we invite
comments as to whether we should amend these regulations to require
applicants to report possible falsification of data.
(4) We invite comments on whether the proposed rule should specify
an evidentiary standard or threshold, such as a certain form or
quantity of information that a sponsor must be aware of before the
sponsor would be required to report possible falsification of data.
(5) We invite comments on whether we should include additional
descriptions of what we consider ``errors'' (beyond the listing of
examples such as typographical errors and transposed numbers or
characters) that sponsors would not be required to report.
(6) We invite comments on the information that should be provided
to FDA when a sponsor reports possible falsification of data, as well
as on whether the regulations should specify what information must be
reported.
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments on this proposal. 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
21 CFR Part 16
Administrative practice and procedure.
21 CFR Part 58
Laboratories, Reporting and recordkeeping requirements.
21 CFR Part 71
Administrative practice and procedure, Color additives,
Confidential business information, Cosmetics, Drugs,
[[Page 7421]]
Reporting and recordkeeping requirements.
21 CFR Part 101
Food labeling, Nutrition, Reporting and recordkeeping requirements.
21 CFR Part 170
Administrative practice and procedure, Food additives, Reporting
and recordkeeping requirements.
21 CFR Part 171
Administrative practice and procedure, Food additives.
21 CFR Part 190
Dietary foods, Foods, Food additives, Reporting and recordkeeping
requirements.
21 CFR Part 312
Drugs, Exports, Imports, Investigations, Labeling, Medical
research, Reporting and recordkeeping requirements, Safety.
21 CFR Part 511
Animal drugs, Medical research, Reporting and recordkeeping
requirements.
21 CFR Part 571
Administrative practice and procedure, Animal feeds, Animal foods,
Food additives.
21 CFR Part 812
Health records, Medical devices, Medical research, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, it is proposed that 21 CFR parts 16,
58, 71, 101, 170, 171, 190, 312, 511, 571, and 812 be amended as
follows:
PART 16--REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION
1. The authority citation for 21 CFR part 16 continues to read as
follows:
Authority: 15 U.S.C. 1451-1461; 21 U.S.C. 141-149, 321-394,
467f, 679, 821, 1034; 28 U.S.C. 2112; 42 U.S.C. 201-262, 263b, 364.
Sec. 16.1 [Amended]
2. Section 16.1 is amended in paragraph (b)(2) by removing
``511.1(c)(1)`` and adding in its place ``511.1(d)(1)'' and by removing
the phrase ``511.1(c)(4) and (d)'' and adding in its place the phrase
``511.1(d)(4) and (e)''.
PART 58--GOOD LABORATORY PRACTICE FOR NONCLINICAL LABORATORY
STUDIES
3. The authority citation for 21 CFR part 58 continues to read as
follows:
Authority: 21 U.S.C. 342, 346, 346a, 348, 351, 352, 353, 355,
360, 360b-360f, 360h-360j, 371, 379e, 381; 42 U.S.C. 216, 262, 263b-
263n.
4. Section 58.11 is added to subpart A to read as follows:
Sec. 58.11 Reporting falsification of data.
(a) When a sponsor becomes aware of information indicating that any
person has, or may have, engaged in the falsification of data in the
course of reporting study results, or in the course of proposing,
designing, performing, recording, supervising, or reviewing studies
conducted by or on behalf of a sponsor or relied on by a sponsor
involving studies subject to this part, the sponsor must report this
information to FDA. A sponsor must report this information regardless
of whether the sponsor has evidence as to the intent of the person who
has, or may have, falsified data. The sponsor must report this
information to FDA promptly, but no later than 45 calendar days after
the sponsor becomes aware of the information. For the purpose of this
section only, the following definitions apply:
(1) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(i) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(ii) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(iii) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(iv) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(2) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(b) Sponsors should not report errors (e.g., typographical errors,
transposed numbers or characters) to FDA under this section.
5. Section 58.217 is transferred to subpart A and redesignated as
Sec. 58.12 and newly redesignated Sec. 58.12 is revised to read as
follows:
Sec. 58.12 Suspension or termination of a testing facility by a
sponsor.
Termination of a testing facility by a sponsor is independent of,
and neither in lieu of nor a precondition to, proceedings or actions
authorized by subpart K of this part. If a sponsor terminates or
suspends a testing facility from further participation in a nonclinical
laboratory study that is being conducted as part of any application for
a research or marketing permit that has been submitted to any Center of
the Food and Drug Administration (whether approved or not), the sponsor
must notify that center in writing within 15 working days of the
action; the notice must include a statement of the reasons for such
action. Suspension or termination of a testing facility by a sponsor
does not relieve it of any obligation under any other applicable
regulation to submit the results of the study to the Food and Drug
Administration.
PART 71--COLOR ADDITIVE PETITIONS
6. The authority citation for 21 CFR part 71 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 351, 355, 360, 360b-360f,
360h-360j, 361, 371, 379e, 381; 42 U.S.C. 216, 262.
7. Section 71.1 is amended by adding paragraph (k) to read as
follows:
Sec. 71.1 Petitions.
* * * * *
(k)(1) When a petitioner becomes aware of information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies conducted by or on behalf of a petitioner, relied on by a
petitioner, or otherwise cited in a petition under this
[[Page 7422]]
part, the petitioner must report this information to the Center for
Food Safety and Applied Nutrition (Center). A petitioner must report
this information regardless of whether the petitioner has evidence as
to the intent of the person who has, or may have, falsified data. The
petitioner must report this information to the Center promptly, but no
later than 45 calendar days after the petitioner becomes aware of the
information. For the purpose of this section only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Petitioners should not report errors (e.g., typographical
errors, transposed numbers or characters) to FDA under paragraph (k) of
this section.
PART 101--FOOD LABELING
8. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342,
343, 348, 371; 42 U.S.C. 243, 264, 271.
9. Section 101.69 is amended by adding paragraph (p) to read as
follows:
Sec. 101.69 Petitions for nutrient content claims.
* * * * *
(p)(1) When a petitioner becomes aware of information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies conducted by or on behalf of a petitioner, relied on by a
petitioner, or otherwise cited in a petition under this part, the
petitioner must report this information to the Center for Food Safety
and Applied Nutrition (Center). A petitioner must report this
information regardless of whether the petitioner has evidence as to the
intent of the person who has, or may have, falsified data. The
petitioner must report this information to the Center promptly, but no
later than 45 calendar days after the petitioner becomes aware of the
information. For the purpose of this section only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Petitioners should not report errors (e.g., typographical
errors, transposed numbers or characters) to FDA under paragraph (p) of
this section.
10. Section 101.70 is amended by adding paragraph (k) to read as
follows:
Sec. 101.70 Petitions for health claims.
* * * * *
(k)(1) When a petitioner becomes aware of information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies conducted by or on behalf of a petitioner, relied on by a
petitioner, or otherwise cited in a petition under this part, the
petitioner must report this information to the Center for Food Safety
and Applied Nutrition (Center). A petitioner must report this
information regardless of whether the petitioner has evidence as to the
intent of the person who has, or may have, falsified data. The
petitioner must report this information to the Center promptly, but no
later than 45 calendar days after the petitioner becomes aware of the
information. For the purpose of this section only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject
[[Page 7423]]
when it came from a source other than the subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Petitioners should not report errors (e.g., typographical
errors, transposed numbers or characters) to FDA under paragraph (k) of
this section.
PART 170--FOOD ADDITIVES
11. The authority citation for 21 CFR part 170 continues to read as
follows:
Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.
12. Section 170.101 is amended by adding paragraph (f) to read as
follows:
Sec. 170.101 Information in a premarket notification for a food
contact substance (FCN).
* * * * *
(f)(1) When a manufacturer or supplier who submits a FCN becomes
aware of information indicating that any person has, or may have,
engaged in the falsification of data in the course of reporting study
results, or in the course of proposing, designing, performing,
recording, supervising, or reviewing studies conducted by or on behalf
of a manufacturer or supplier, relied on by a manufacturer or supplier,
or otherwise cited in the notification under this part, the
manufacturer or supplier must report this information to the Center for
Food Safety and Applied Nutrition (Center). A manufacturer or supplier
must report this information regardless of whether the manufacturer or
supplier has evidence as to the intent of the person who has, or may
have, falsified data. The manufacturer or supplier must report this
information to the Center promptly, but no later than 45 calendar days
after the manufacturer or supplier becomes aware of the information.
For the purpose of this section only, the following definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Manufacturers or suppliers should not report errors (e.g.,
typographical errors, transposed numbers or characters) to FDA under
paragraph (f) of this section.
PART 171--FOOD ADDITIVE PETITIONS
13. The authority citation for 21 CFR part 171 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 371.
14. Section 171.1 is amended by adding paragraph (o) to read as
follows:
Sec. 171.1 Petitions.
* * * * *
(o)(1) When a petitioner becomes aware of information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies conducted by or on behalf of a petitioner, relied on by a
petitioner, or otherwise cited in the petition under this part, the
petitioner must report this information to the Center for Food Safety
and Applied Nutrition (Center). A petitioner must report this
information regardless of whether the petitioner has evidence as to the
intent of the person who has, or may have, falsified data. The
petitioner must report this information to the Center promptly, but no
later than 45 calendar days after the petitioner becomes aware of the
information. For the purpose of this section only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Petitioners should not report errors (e.g., typographical
errors, transposed numbers or characters) to FDA under paragraph (o) of
this section.
PART 190--DIETARY SUPPLEMENTS
15. The authority citation for 21 CFR part 190 is revised to read
as follows:
Authority: 21 U.S.C. 321(ff), 331, 342, 350(b), 371.
16. Section 190.6 is amended by adding paragraph (g) to read as
follows:
[[Page 7424]]
Sec. 190.6 Requirement for premarket notification.
* * * * *
(g)(1) When a manufacturer or distributor who submits a
notification becomes aware of information indicating that any person
has, or may have, engaged in the falsification of data in the course of
reporting study results, or in the course of proposing, designing,
performing, recording, supervising, or reviewing studies conducted by
or on behalf of a manufacturer or distributor, relied on by a
manufacturer or distributor, or otherwise cited in the petition under
this part, the manufacturer or distributor must report this information
to the Center for Food Safety and Applied Nutrition (Center). A
manufacturer or distributor must report this information regardless of
whether the manufacturer or distributor has evidence as to the intent
of the person who has, or may have, falsified data. The manufacturer or
distributor must report this information to the Center promptly, but no
later than 45 calendar days after the manufacturer or distributor
becomes aware of the information. For the purpose of this section only,
the following definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Manufacturers or distributors should not report errors (e.g.,
typographical errors, transposed numbers or characters) to FDA under
paragraph (g) of this section.
PART 312--INVESTIGATIONAL NEW DRUG APPLICATION
17. The authority citation for 21 CFR part 312 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 371,
381, 382, 383, 393; 42 U.S.C. 262.
18. Section 312.56 is amended by revising the section heading and
by adding new paragraph (e) to read as follows:
Sec. 312.56 Review of ongoing investigations; reporting
falsification of data.
* * * * *
(e)(1) When a sponsor becomes aware of information indicating that
any person has, or may have, engaged in the falsification of data in
the course of reporting study results, or in the course of proposing,
designing, performing, recording, supervising, or reviewing studies
conducted by or on behalf of a sponsor or relied on by a sponsor
involving studies subject to this part, the sponsor must report this
information to the Center for Drug Evaluation and Research (Center). A
sponsor must report this information regardless of whether the sponsor
has evidence as to the intent of the person who has, or may have,
falsified data. The sponsor must report this information to the Center
promptly, but no later than 45 calendar days after the sponsor becomes
aware of the information. For the purpose of this section only, the
following definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Sponsors should not report errors (e.g., typographical errors,
transposed numbers or characters) to FDA under paragraph (e) of this
section.
PART 511--NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE
19. The authority citation for 21 CFR part 511 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 353, 360b, 371.
20. Section 511.1 is amended by redesignating paragraphs (c), (d),
(e), (f), and (g) as paragraphs (d), (e), (f), (g), and (h),
respectively, and by adding new paragraph (c) to read as follows:
Sec. 511.1 New animal drugs for investigational use exempt from
section 512(a) of the act.
* * * * *
(c) Reporting falsification of data. (1) When a sponsor becomes
aware of information indicating that any person has, or may have,
engaged in the falsification of data in the course of reporting study
results, or in the course of proposing, designing, performing,
recording, supervising, or reviewing studies conducted by or on behalf
of a sponsor or relied on by a sponsor, the sponsor must report this
information to the Center for Veterinary Medicine (Center). A sponsor
must report this information regardless of whether the sponsor has
evidence as to the intent of the person who has, or may have, falsified
data. The sponsor must report this information to the Center promptly,
but no later than 45 calendar days after the sponsor becomes aware of
the
[[Page 7425]]
information. For the purpose of this paragraph only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Sponsors should not report errors (e.g., typographical errors,
transposed numbers or characters) to FDA under paragraph (c) of this
section.
* * * * *
PART 571--FOOD ADDITIVE PETITIONS
21. The authority citation for 21 CFR part 571 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 371; 42 U.S.C. 241.
22. Section 571.1 is amended by adding paragraph (l) to read as
follows:
Sec. 571.1 Petitions.
* * * * *
(l)(1) When a petitioner becomes aware of information indicating
that any person has, or may have, engaged in the falsification of data
in the course of reporting study results, or in the course of
proposing, designing, performing, recording, supervising, or reviewing
studies conducted by or on behalf of the petitioner, relied on by the
petitioner, or otherwise cited in the petition under this part, the
petitioner must report this information to the Center for Food Safety
and Applied Nutrition (Center). A petitioner must report this
information regardless of whether the petitioner has evidence as to the
intent of the person who has, or may have, falsified data. The
petitioner must report this information to the Center promptly, but no
later than 45 calendar days after the petitioner becomes aware of the
information. For the purpose of this section only, the following
definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting data in such a way that the data do not represent what
actually occurred. Examples of falsification of data include, but are
not limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Petitioners should not report errors (e.g., typographical
errors, transposed numbers or characters) to FDA under paragraph (l) of
this section.
PART 812--INVESTIGATIONAL DEVICE EXEMPTIONS
23. The authority citation for 21 CFR part 812 continues to read as
follows:
Authority: 21 U.S.C. 331, 351, 352, 353, 355, 360, 360c-360f,
360h-360j, 371, 372, 374, 379e, 381, 382, 383; 42 U.S.C. 216, 241,
262, 263b-263n.
24. Section 812.2 is amended by revising paragraph (c) introductory
text to read as follows:
Sec. 812.2 Applicability.
* * * * *
(c) Exempted investigations. This part, with the exception of
Sec. Sec. 812.46(d) and 812.119, does not apply to investigations of
the following categories of devices:
* * * * *
25. Section 812.46 is amended by adding paragraph (d) to read as
follows:
Sec. 812.46 Monitoring investigations.
* * * * *
(d) Falsification. (1) When a sponsor becomes aware of information
indicating that any person has, or may have, engaged in the
falsification of data in the course of reporting study results, or in
the course of proposing, designing, performing, recording, supervising,
or reviewing studies conducted by or on behalf of a sponsor or relied
on by a sponsor involving studies subject to this part, the sponsor
must report this information to FDA. A sponsor must report this
information regardless of whether the sponsor has evidence as to the
intent of the person who has, or may have, falsified data. The sponsor
must report this information to FDA promptly, but no later than 45
calendar days after the sponsor becomes aware of the information. Such
reports should be submitted to the Center with jurisdiction over the
product or clinical trial. For studies involving devices regulated by
the Center for Devices and Radiological Health (CDRH), reports should
be submitted to the Division of Bioresearch Monitoring (HFZ-310),
Office of Compliance, Center for Devices and Radiological Health, Food
and Drug Administration. For studies involving products regulated by
the Center for Biologics Evaluation and Research (CBER), reports should
be submitted to the Division of Inspections and Surveillance (HFM-650),
Office of Compliance and Biologics Quality, Center for Biologics
Evaluation and Research, Food and Drug Administration. For the purpose
of this section only, the following definitions apply:
(i) Falsification of data means creating, altering, recording, or
omitting
[[Page 7426]]
data in such a way that the data do not represent what actually
occurred. Examples of falsification of data include, but are not
limited to, the following:
(A) Creating data that were never obtained (e.g., making up data or
results and recording or reporting them; reporting enrollment in a
study of a subject who did not exist; forging the signature on an
informed consent form);
(B) Altering data by replacing original data with something
different that does not accurately reflect study conduct or results
(e.g., changing a laboratory measurement to a less extreme deviation
from normal);
(C) Recording or obtaining data from a specimen, sample, or test
whose origin is not accurately described or in a way that does not
accurately reflect the data (e.g., changing the date of a specimen,
sample, or test; adding a substance not called for in the study to a
specimen or sample; identifying a specimen, sample, or test as coming
from a specific subject when it came from a source other than the
subject);
(D) Omitting data that were obtained and would be appropriate for
recording based on study design and conduct (e.g., not recording
exclusionary medical history or prohibited concomitant medications or
treatments; omitting data so that a statistical analysis yields a
result that would not have been obtained had all data been analyzed).
(ii) The term data includes, but is not limited to, individual
facts, tests, specimens, samples, results, statistics, items of
information, or statements made by individuals.
(2) Sponsors should not report errors (e.g., typographical errors,
transposed numbers or characters) to FDA under paragraph (d) of this
section.
Dated: February 12, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-3123 Filed 2-18-10; 8:45 am]
BILLING CODE 4160-01-S