I 
110TH CONGRESS 
1ST SESSION H. R. 1561 
To amend the Public Health Service Act and the Federal Food, Drug, 
and Cosmetic Act to improve drug safety and oversight, and for other 
purposes. 
IN THE HOUSE OF REPRESENTATIVES 
MARCH 19, 2007 
Mr. WAXMAN (for himself and Mr. MARKEY) introduced the following bill; 
which was referred to the Committee on Energy and Commerce 
A BILL 
To amend the Public Health Service Act and the Federal 
Food, Drug, and Cosmetic Act to improve drug safety 
and oversight, and for other purposes. 
Be it enacted by the Senate and House of Representa-
tives of the United States of America in Congress assembled, 
SECTION 1. SHORT TITLE. 
This Act may be cited as the ‘‘Enhancing Drug Safe-
ty and Innovation Act of 2007’’. 
SEC. 2. TABLE OF CONTENTS. 
The table of contents for this Act is as follows: 
Sec. 1. Short title. 
Sec. 2. Table of contents. 
TITLE I—RISK EVALUATION AND MITIGATION STRATEGIES 
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Sec. 101. Risk evaluation and mitigation strategies. 
Sec. 102. Enforcement. 
Sec. 103. Regulation of biological products. 
Sec. 104. No effect on withdrawal or suspension of approval. 
Sec. 105. Drugs subject to an abbreviated new drug application. 
Sec. 106. Conforming amendments. 
Sec. 107. Resources. 
Sec. 108. Drug labeling. 
Sec. 109. Factory inspections. 
Sec. 110. Study on integration of expertise of Office of Surveillance and Epide-
miology. 
Sec. 111. Benefit-risk assessments. 
Sec. 112. Effective date and applicability. 
Sec. 113. Rule of construction regarding pediatric studies. 
Sec. 114. Authorization of appropriations. 
TITLE II—REAGAN-UDALL INSTITUTE FOR APPLIED BIOMEDICAL 
RESEARCH 
Sec. 201. The Reagan-Udall Institute for Applied Biomedical Research. 
TITLE III—CLINICAL TRIALS 
Sec. 301. Clinical trial registry database and clinical trial results database. 
TITLE IV—CONFLICTS OF INTEREST 
Sec. 401. Conflicts of interest. 
TITLE I—RISK EVALUATION AND 
MITIGATION STRATEGIES 
SEC. 101. RISK EVALUATION AND MITIGATION STRATEGIES. 
Section 505 of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 355) is amended by adding at the end the 
following: 
‘‘(o) RISK EVALUATION AND MITIGATION STRAT-
EGY.— 
‘‘(1) IN GENERAL.—In the case of any drug 
subject to subsection (b) or to section 351 of the 
Public Health Service Act for which a risk evalua-
tion and mitigation strategy is approved as provided 
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for in this subsection, the applicant shall comply 
with the requirements of such strategy. 
‘‘(2) DEFINITIONS.—In this subsection: 
‘‘(A) ADVERSE DRUG EXPERIENCE.—The 
term ‘adverse drug experience’ means any ad-
verse event associated with the use of a drug in 
humans, whether or not considered drug re-
lated, including— 
‘‘(i) an adverse event occurring in the 
course of the use of the drug in profes-
sional practice; 
‘‘(ii) an adverse event occurring from 
an overdose of the drug, whether acci-
dental or intentional; 
‘‘(iii) an adverse event occurring from 
abuse of the drug; 
‘‘(iv) an adverse event occurring from 
withdrawal of the drug; and 
‘‘(v) any failure of expected pharma-
cological action of the drug. 
‘‘(B) SERIOUS
ADVERSE
DRUG
EXPERI-
ENCE.—The term ‘serious adverse drug experi-
ence’ is an adverse event that— 
‘‘(i) results in— 
‘‘(I) death; 
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‘‘(II) an adverse drug experience 
that places the patient at immediate 
risk of death from the adverse drug 
experience as it occurred (not includ-
ing an adverse drug experience that 
might have caused death had it oc-
curred in a more severe form); 
‘‘(III) inpatient hospitalization or 
prolongation of existing hospitaliza-
tion; 
‘‘(IV) a persistent or significant 
incapacity or substantial disruption of 
the ability to conduct normal life 
functions; or 
‘‘(V) a congenital anomaly or 
birth defect; or 
‘‘(ii) based on appropriate medical 
judgment, may jeopardize the patient and 
may require a medical or surgical interven-
tion to prevent an outcome described under 
clause (i). 
‘‘(C) SERIOUS
RISK.—The term ‘serious 
risk’ means a risk of a serious adverse drug ex-
perience. 
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‘‘(D) UNEXPECTED
SERIOUS
RISK.—The 
term ‘unexpected serious risk’ means a serious 
adverse drug experience that is not listed in the 
labeling of a drug, or that may be sympto-
matically and pathophysiologically related to an 
adverse drug experience identified in the label-
ing, but differs from such adverse drug experi-
ence because of greater severity, specificity, or 
prevalence. 
‘‘(E) SIGNAL OF A SERIOUS RISK.—The 
term ‘signal of a serious risk’ means informa-
tion related to a serious adverse drug experi-
ence associated with use of a drug and derived 
from— 
‘‘(i) a clinical trial; 
‘‘(ii) adverse event reports; 
‘‘(iii) a post-approval study, including 
a study under paragraph (4)(D); or 
‘‘(iv) peer-reviewed biomedical lit-
erature. 
‘‘(F) NEW
SAFETY
INFORMATION.—The 
term ‘new safety information’ with respect to a 
drug means information about— 
‘‘(i) a serious risk or an unexpected 
serious risk associated with use of the drug 
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that the Secretary has become aware of 
since the last assessment of the approved 
risk evaluation and mitigation strategy for 
the drug; or 
‘‘(ii) the effectiveness of the approved 
risk evaluation and mitigation strategy for 
the drug obtained since the last assessment 
of such strategy. 
‘‘(3) REQUIRED ELEMENTS OF A RISK EVALUA-
TION AND MITIGATION STRATEGY.—The risk evalua-
tion and mitigation strategy for a drug shall re-
quire— 
‘‘(A)(i) labeling for the drug for use by 
health care providers as approved under sub-
section (c); and 
‘‘(ii) for the first 2 years (or for such pe-
riod as the Secretary determines on a case-by- 
case basis to be appropriate) after the drug or 
a new indication for the drug is approved, inclu-
sion in the labeling and any direct-to-consumer 
advertisements of a unique symbol indicating 
the newly approved status of the drug or indica-
tion; 
‘‘(B)(i) submission of reports for the drug 
as required under subsection (k); and 
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‘‘(ii) for a drug that is a vaccine— 
‘‘(I) analysis of reports to the Vaccine 
Adverse 
Event 
Reporting 
Systems 
(VAERS); or 
‘‘(II) surveillance using the Vaccine 
Safety Datalink (VSD) or successor data-
bases; 
‘‘(C) a pharmacovigilance statement— 
‘‘(i) as to whether the reports under 
subparagraph (B)(i) or, for a vaccine, the 
analysis and surveillance under subpara-
graph (B)(ii), and the periodic assessment 
under subparagraph (E), are sufficient to 
assess the serious risks and to identify un-
expected serious risks of the drug; and 
‘‘(ii) if such reports, such analysis and 
surveillance, and such periodic assessment 
are not sufficient to assess the serious 
risks and to identify unexpected serious 
risks of the drug, that describes what 
study or studies of the drug are required 
under paragraph (4)(D) or what clinical 
trial or trials of the drug are required 
under paragraph (4)(E); 
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‘‘(D) 
a 
justification 
for 
the 
pharmacovigilance statement in subparagraph 
(C) that takes into consideration— 
‘‘(i) the estimated size of the treat-
ment population for the drug; 
‘‘(ii) the seriousness of the disease or 
condition that the drug is used to treat or 
prevent; 
‘‘(iii) the expected or actual duration 
of treatment with the drug; 
‘‘(iv) the availability and safety of a 
drug or other treatment, if any, for such 
disease or condition to which the safety of 
the drug may be compared; and 
‘‘(v) the seriousness of the risk at 
issue and its background incidence in the 
population; and 
‘‘(E) a timetable for submission of assess-
ments of the strategy, that— 
‘‘(i) shall be no less frequently than 
once annually for the first 3 years after 
the drug is initially approved under sub-
section (c) or licensed under section 351 of 
the Public Health Service Act; 
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‘‘(ii) shall include an assessment in 
the seventh year after the drug is so ap-
proved; and 
‘‘(iii) subject to clause (ii), for subse-
quent years— 
‘‘(I) shall be at a frequency speci-
fied in the strategy; 
‘‘(II) may be increased or re-
duced in frequency as necessary as 
provided 
for 
in 
paragraph 
(6)(B)(iv)(VI); and 
‘‘(III) may be eliminated after 
the 3-year period described in clause 
(i) if the Secretary determines that se-
rious risks of the drug have been ade-
quately identified and assessed and 
are being adequately managed. 
‘‘(4) ADDITIONAL POTENTIAL ELEMENTS OF A 
RISK EVALUATION AND MITIGATION STRATEGY.— 
‘‘(A) IN GENERAL.—The Secretary may re-
quire that the risk evaluation and mitigation 
strategy for a drug include 1 or more of the ad-
ditional elements described in this paragraph, 
so long as the Secretary makes the determina-
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tion required with respect to each additional in-
cluded element. 
‘‘(B) MEDGUIDE; PATIENT
PACKAGE
IN-
SERT.—The risk evaluation and mitigation 
strategy for a drug may require that the appli-
cant develop for distribution to each patient 
when the drug is dispensed— 
‘‘(i) a Medication Guide, as provided 
for under part 208 of title 21, Code of 
Federal Regulations (or any successor reg-
ulations); or 
‘‘(ii) a patient package insert, if the 
Secretary determines that such insert may 
help mitigate a serious risk of the drug. 
‘‘(C) COMMUNICATION
PLAN.—The risk 
evaluation and mitigation strategy for a drug 
may require that the applicant conduct a com-
munication plan to health care providers, if, 
with respect to such drug, the Secretary deter-
mines that such plan may support implementa-
tion of an element of the strategy. Such plan 
may include— 
‘‘(i) sending letters to health care pro-
viders; 
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‘‘(ii) disseminating information about 
the elements of the risk evaluation and 
mitigation strategy to encourage implemen-
tation by health care providers of compo-
nents that apply to such health care pro-
viders, or to explain certain safety proto-
cols (such as medical monitoring by peri-
odic laboratory tests); or 
‘‘(iii) disseminating information to 
health care providers through professional 
societies about any serious risks of the 
drug and any protocol to assure safe use. 
‘‘(D) POST-APPROVAL STUDIES.—The risk 
evaluation and mitigation strategy for a drug 
may require that the applicant conduct, or pro-
vide that the Secretary will conduct, an appro-
priate post-approval study, such as a prospec-
tive or retrospective observational study (includ-
ing through the systematic use of established 
health care networks and databases), of the 
drug (with a target schedule for completing the 
study and reporting the results to the Sec-
retary), if the Secretary determines the reports, 
analysis and surveillance, and periodic assess-
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ments referred to in paragraph (3)(C) are not 
sufficient to— 
‘‘(i) assess evidence of a serious risk 
related to the safety or effectiveness of the 
drug; or 
‘‘(ii) identify unexpected serious risks 
in domestic populations who use the drug, 
including populations not included in stud-
ies used to approve the drug (such as older 
people, people with comorbidities, pregnant 
women, or children). 
‘‘(E) POST-APPROVAL CLINICAL TRIALS.— 
The risk evaluation and mitigation strategy for 
a drug may require that the applicant for a 
drug for which there is no effective approved 
application under subsection (j) of this section 
as of the date that the requirement is first im-
posed conduct an appropriate post-approval 
clinical trial of the drug (with a target schedule 
for completing the clinical trial and reporting 
the results to the Secretary) to be included in 
the clinical trial registry database and clinical 
trial results database provided for under section 
402(i) of the Public Health Service Act, if the 
Secretary determines that a study or studies 
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under subparagraph (D) will likely be inad-
equate to assess evidence of a serious risk re-
lated to the safety or effectiveness of the drug. 
‘‘(F) PRECLEARANCE.— 
‘‘(i) IN GENERAL.—The risk evalua-
tion and mitigation strategy for a drug 
may require that the applicant submit to 
the Secretary advertisements of the drug 
for preclearance, if the Secretary deter-
mines that such preclearance is necessary 
to ensure compliance with section 502(n) 
with respect to the disclosure of informa-
tion about a serious risk listed in the label-
ing of the drug. The advertisements re-
quired to be submitted under the preceding 
sentence shall be reviewed and cleared by 
the Secretary within 45 days of submis-
sion. 
‘‘(ii) SPECIFICATION
OF
ADVERTISE-
MENTS.—The Secretary may specify the 
advertisements required to be submitted 
under clause (i). 
‘‘(G) SPECIFIC DISCLOSURES.— 
‘‘(i) IN GENERAL.—The risk evalua-
tion and mitigation strategy for a drug 
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may require that the applicant include in 
advertisements of the drug a specific dis-
closure— 
‘‘(I) of the date the drug was ap-
proved and that the existing informa-
tion may not have identified or al-
lowed for full assessment of all serious 
risks of using the drug, if the Sec-
retary determines that such disclosure 
is necessary to protect public health 
and safety; or 
‘‘(II) about a serious adverse 
event listed in the labeling of the drug 
or a protocol to ensure safe use de-
scribed in the labeling of the drug, if 
the Secretary determines that such 
advertisements lacking such disclosure 
would be false or misleading. 
‘‘(ii) SPECIFICATION
OF
ADVERTISE-
MENTS.—The Secretary may specify the 
advertisements required to include a spe-
cific disclosure under clause (i). 
‘‘(H) 
TEMPORARY
MORATORIUM.—The 
risk evaluation and mitigation strategy for a 
drug may require that for a fixed period after 
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initial approval, not to exceed 3 years, the ap-
plicant not issue or cause to be issued direct- 
to-consumer advertisements of the drug, if the 
Secretary determines that disclosure under sub-
paragraph (G) is inadequate to protect public 
health and safety, and that such prohibition is 
necessary to protect public health and safety 
while additional information about serious risks 
of the drug is collected, considering— 
‘‘(i) the number of patients who may 
be treated with the drug; 
‘‘(ii) the seriousness of the condition 
for which the drug will be used; 
‘‘(iii) the serious adverse events listed 
in the labeling of the drug; 
‘‘(iv) the extent to which patients have 
access to other approved drugs in the 
pharmacological class of the drug and with 
the same intended use as the drug; and 
‘‘(v) the extent to which clinical trials 
used to approve the drug may not have 
identified serious risks that might occur 
among patients expected to be treated with 
the drug. 
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‘‘(5) RESTRICTIONS
ON
DISTRIBUTION
OR 
USE.— 
‘‘(A) IN GENERAL.—If the Secretary deter-
mines that a drug shown to be effective can be 
safely used only if distribution or use of such 
drug is restricted, the Secretary may require as 
elements of the risk evaluation and mitigation 
strategy such restrictions on distribution or use 
as are needed to ensure safe use of the drug. 
‘‘(B) LIMITS ON RESTRICTIONS.—Such re-
strictions under subparagraph (A) shall— 
‘‘(i) be commensurate with the spe-
cific risk presented by the drug; 
‘‘(ii) not be unduly burdensome on pa-
tient access to the drug, particularly for 
patients with serious or life-threatening 
diseases or conditions; and 
‘‘(iii) to the extent practicable, con-
form with restrictions on distribution or 
use for other drugs with similar risks, so 
as to minimize the burden on the health 
care delivery system. 
‘‘(C) ELEMENTS.—The restrictions on dis-
tribution or use described in subparagraph (A) 
shall include 1 or more goals to evaluate or 
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mitigate a serious risk listed in the labeling of 
the drug and may require that— 
‘‘(i) health care providers that pre-
scribe the drug have special training or ex-
perience, or are specially certified; 
‘‘(ii) pharmacies, practitioners, or 
health care settings that dispense the drug 
are specially certified; 
‘‘(iii) the drug be dispensed to pa-
tients only in certain health care settings, 
such as hospitals; 
‘‘(iv) the drug be dispensed to pa-
tients with evidence or other documenta-
tion of safe-use conditions, such as labora-
tory test results; 
‘‘(v) each patient using the drug be 
subject to certain monitoring; or 
‘‘(vi) each patient using the drug be 
enrolled in a registry. 
‘‘(D) IMPLEMENTATION SYSTEM.—The re-
strictions on distribution or use described in 
subparagraph (A) may require a system 
through which the applicant is able to— 
‘‘(i) monitor and evaluate implementa-
tion of the restrictions by health care pro-
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viders, pharmacists, patients, and other 
parties in the health care system who are 
responsible for implementing the restric-
tions; 
‘‘(ii) work to improve implementation 
of the restrictions by health care providers, 
pharmacists, patients, and other parties in 
the health care system who are responsible 
for implementing the restrictions; and 
‘‘(iii) stop distribution of the drug to 
those health care providers, pharmacists, 
and other parties in the health care sys-
tem— 
‘‘(I) who are responsible for im-
plementing the restrictions; and 
‘‘(II) whom the applicant knows 
have failed to meet their responsibil-
ities for implementing the restrictions, 
after the applicant has informed such 
party of such failure and such party 
has not remedied such failure. 
‘‘(E) PATENTS.—The Secretary shall not 
approve a risk evaluation and mitigation strat-
egy for a drug, or any modification to the strat-
egy, under paragraph (6) if— 
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‘‘(i) the strategy includes a restriction 
on distribution or use described in sub-
paragraph (A) that is protected by a pat-
ent; 
‘‘(ii) such patent was issued after the 
date of the enactment of this subsection; 
and 
‘‘(iii) such patent would prohibit or 
impair the application of such restriction 
under section 505(j)(2)(E)(i)(VII) to a 
drug that is the subject of an abbreviated 
new drug application. 
‘‘(6) SUBMISSION AND REVIEW OF RISK EVAL-
UATION AND MITIGATION STRATEGY.— 
‘‘(A) PROPOSED
RISK
EVALUATION
AND 
MITIGATION STRATEGY.— 
‘‘(i) INITIAL
APPROVAL.—An appli-
cant shall include a proposed risk evalua-
tion and mitigation strategy in an applica-
tion under subsection (b) or section 351 of 
the Public Health Service Act for initial 
approval of the drug. 
‘‘(ii) APPROVAL
OF
NEW
INDICA-
TION.—If no risk evaluation and mitiga-
tion strategy for the drug is in effect under 
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