Drug Safety: A Side-by-Side Comparison of Bills in the 110th Congress

Drug Safety:
A Side-by-Side Comparison of
Bills in the 110th Congress
March 13, 2007
Susan Thaul
Specialist in the Regulation of Prescription Drugs and Biologics
Domestic Social Policy Division

Drug Safety: A Side-by-Side Comparison
of Bills in the 110th Congress
Summary
Members of Congress and the public are increasingly concerned about the
ability of the Food and Drug Administration (FDA) to ensure that the drugs sold in
the United States are safe and effective. In November 2004, FDA asked the Institute
of Medicine (IOM) to assess the current system for evaluating and ensuring drug
safety and to make recommendations to improve risk assessment, surveillance, and
the safe use of drugs. IOM released The Future of Drug Safety: Promoting and
Protecting the Health of the Public in September 2006, and FDA issued its response
in January 2007. The following drug safety bills have been introduced in the 110th
Congress: S. 468 / H.R. 788, S. 484, and H.R. 1165.
Although the legislation and the IOM report address many of the same drug
safety issues, the bills differ in their treatment of FDA authority to require action and
to enforce compliance, comparative effectiveness studies, and how to fund any
additional agency activities. For example, S. 468 / H.R. 788 would strengthen FDA’s
post-approval drug safety activities by creating a new Center for Postmarket
Evaluation and Research for Drugs and Biologics. The other bills would leave these
activities where they currently reside in the Center for Drug Evaluation and Research.
All the bills would allow the FDA to penalize (through civil fines, injunctions, or
withdrawal of marketing approval or licensure) drug manufacturers who did not
conduct required postmarket studies or who failed to report study results.
The IOM committee recommended that Congress provide substantially
increased resources to FDA to bolster its drug safety activities. S. 468 / H.R. 788
would authorize appropriations to carry out the bill’s provisions, S. 484 would rely
on user fees, expanding FDA’s existing authority to use such fees, and H.R. 1165
does not address funding.

Contents
Background ..................................................1
Report Highlights..............................................2
FDA organization..........................................2
FDA authority to require action and to enforce compliance.........2
Comparative-effectiveness studies.............................3
FDA funding.............................................3
Comparison of Drug Safety Provisions.............................4
Organizational culture......................................4
Science and expertise.......................................7
Regulation ..............................................17
Communication ..........................................24
Resources ...............................................26
List of Tables
Table 1. Comparison of Drug Safety Provisions in S. 468 / H.R. 788,
S. 484, and H.R. 1165 in Relation to Recommendations
in the Institute of Medicine September 2006 Report and
the Food and Drug Administration’s January 2007 Response............4

Drug Safety:
A Side-by-Side Comparison
of Bills in the 110th Congress
Background
Members of Congress and the public are increasingly concerned about the
ability of the Food and Drug Administration (FDA) to ensure that the drugs sold in
the United States are safe and effective. Legislators, industry, the public, and FDA
scientists have raised questions about FDA’s collection and release of safety data,
and whether the agency has the authority and resources to ensure adequate research
over the marketing life of the pharmaceutical products it regulates.
In 2004, the regulatory, medical, and industry debate became very public with
reports of cardiovascular hazards posed by the pain medicine Vioxx (one of several
COX-2 nonsteroidal antiflammatory drugs then on the market), and of children facing
increased risk of suicidal thoughts and actions when taking certain antidepressants
(such as the selective serotonin reuptake inhibitors Paxil and Zoloft). Not only was
Congress asking whether the manufacturers knew of these risks while continuing to
market the drug, but also whether FDA should have known of the risks and done
more to protect the public.
At the height of public and Congressional attention, FDA asked the Institute of
Medicine (IOM) to “conduct an independent assessment of the current system for
evaluating and ensuring drug safety postmarketing and make recommendations to
improve risk assessment, surveillance, and the safe use of drugs.” IOM released its¹
report in September 2006. FDA issued its response in January 2007 and noted
relevant activities the agency has begun and others it has planned.² Among the
planned activities are those in its proposal for a reauthorization of the prescription
drug user fee program (PDUFA IV).³

¹ Institute of Medicine (IOM), The Future of Drug Safety: Promoting and Protecting the
Health of the Public, Alina Baciu, Kathleen Stratton, Sheila P. Burke, Editors, Committee
on the Assessment of the US Drug Safety System, Board on Population Health and Public
Health Practice (Washington, DC: National Academies Press, 2006).
² Food and Drug Administration (FDA), “The Future of Drug Safety — Promoting and
Protecting the Health of the Public: FDA’s Response to the Institute of Medicine’s 2006
Report,” January 2007.
³ Congress first gave FDA authority to collect these fees with the Prescription Drug User
Fee Act of 1992; reauthorized twice, the current authority expires Oct. 1, 2007. See CRS
Report RL33914, The Prescription Drug User Fee Act (PDUFA): Background and Issues
for PDUFA IV Reauthorization, by Susan Thaul.

In the meantime, several Members of Congress have introduced bills to address
drug safety and FDA’s role in protecting the public’s health.
Report Highlights
This report provides a side-by-side comparison of:
^!Institute of Medicine: recommendations in its September 2006
report, The Future of Drug Safety: Promoting and Protecting the
Health of the Public;
^!Food and Drug Administration: announced actions and plans to
address problems identified in the IOM report;
^!S. 468 / H.R. 788 (the Food and Drug Administration Safety Act of

2007), introduced on January 31, 2007, by Senators Grassley, Dodd,

Mikulski, and Bingaman, and Representatives Tierney and Ramstad;
^!S. 484 (the Enhancing Drug Safety and Innovation Act of 2007),
introduced on February 1, 2007, by Senators Enzi and Kennedy;⁴ and
^!H.R. 1165 (the Swift Approval, Full Evaluation (SAFE) Drug Act),
introduced on February 16, 2007, by Representative Markey.
The bills and the IOM report address many of the same issues, often with similar
approaches though at times with major differences. The IOM report addressed only
drugs, not biological products (e.g., vaccines), in keeping with the charge FDA gave
it. FDA’s response to the IOM recommendations, therefore, relates to drugs, but also
states that the approach to drug safety is relevant to all medical products. All the bills
would amend the Federal Food, Drug, and Cosmetic Act (regarding the regulation of
drugs); S. 484 would also amend the Public Health Service Act (regarding the
regulation of biologics). Highlighted below are a few of the more significant items
regarding drug safety.
FDA organization. S. 468/H.R. 788 would remove the post-approval drug
safety activities from FDA’s Center for Drug Evaluation and Research (CDER) and
create a new Center for Postmarket Evaluation and Research for Drugs and Biologics
(the Center). The IOM report does not suggest that approach to strengthen FDA’s
postmarket activities, nor do the other pending bills.
FDA authority to require action and to enforce compliance. The bills
and the IOM recommendations aim to strengthen FDA’s ability to make sure drug
manufacturers (application sponsors) appropriately design and conduct postmarket
studies and disclose the results to the public. S. 468/H.R. 788 lays out requirements
that the new Center for Postmarket Evaluation and Research for Drugs and Biologics
would administer; S. 484 would achieve this with a process it calls a Risk Evaluation
and Mitigation Strategy (REMS); and H.R. 1165 would allow the Secretary to require
certain studies. The IOM recommended and all the bills would allow the Secretary
to penalize (through civil fines, injunctions, or withdrawal of marketing approval or

⁴ This report covers Title I (Risk Evaluation and Mitigation Strategies) of S. 484; it does not
cover Title II (Reagan-Udall Institute for Applied Biomedical Research), Title III (Clinical
Trials), or Title IV (Conflicts of Interest).

licensure) sponsors who do not conduct required studies or complete them on time,
or who fail to report study results.
Comparative-effectiveness studies. The IOM report and the bills address
the need for FDA authority to require pre- and postmarket studies. S. 468 alone
would give FDA the authority to require that those studies compare a drug’s safety
and effectiveness with that of other drugs.
FDA funding. All three bills would require a variety of drug safety activities.
They differ in how to fund them. S. 468 / H.R. 788 would authorize appropriations
to carry out the bill’s provisions; S. 484 would rely on user fees, expanding FDA’s
existing authority to use such fees; and H.R. 1165 does not address funding. The
IOM committee not only recommended that Congress provide “substantially
increased resources” to FDA, but noted that all its other recommendations could not
be implemented without those resources.
Table 1, beginning on page 4, addresses the range of FDA drug safety activities
that the IOM recommended, along with FDA’s response, and activities that the bills
would authorize or require. The table structure follows the 25 IOM
recommendations within the five categories of organizational culture, science and
expertise, regulation, communication, and resources.⁵

⁵ CRS Report RL32797, Drug Safety and Effectiveness: Issues and Action Options After
FDA Approval, by Susan Thaul, addresses many of the topics covered in the IOM report and
the Senate bills. The IOM report also addressed clinical trial registration and results
database requirements; a separate CRS Report RL32832, Clinical Trials Reporting and
Publication, by Erin D. Williams, describes and discusses those recommendations.

CRS-4
Table 1. Comparison of Drug Safety Provisions in S. 468 / H.R. 788, S. 484, and H.R. 1165
in Relation to Recommendations in the Institute of Medicine September 2006 Report
and the Food and Drug Administration’s January 2007 Response
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^va^tⁱ^v^e^d^r^{ugs a}ⁿ^d^eⁿ^surⁱ^{ng d}^r^{ug sa}^fe^t^y^activ^{ities, in}^clu^dⁱⁿ^g^w^o^r^k^au^t^h^ori^{ze appropri}^a^tⁱ^oⁿ^s^f^o^r^d^r^{ug use}^r^fe^e^s^m^a^y^b^e^use^d
^er^th^{e p}^r^o^d^u^ct’^s^lif^ecy^{cle, th}^{e co}^m^m^ittee^to^w^a^r^d^id^en^tif^yⁱⁿ^g^an^d^saf^e^ty^activ^{ities [}^s^{ee b}^e^lo^w^]^.^{to in}^clu^d^{e th}^{e rev}ⁱ^ew^an^d
^m^m^eⁿ^d^{s th}^{at Co}ⁿ^g^r^{ess sh}^o^u^ldⁱⁿ^tr^o^d^u^ce^a^sse^ssi^{ng r}ⁱ^{sk m}^a^na^ge^m^e^nt^im^p^l^em^en^tatioⁿ^o^f^th^{e Risk}
^eci^fi^{c s}^a^fety-rel^ated^p^erform^aⁿ^{ce goal}^sⁱⁿ^an^{d com}^m^uⁿⁱ^cation^tools^;^Ev^alu^a^tioⁿ^an^d^Mitig^atioⁿ
^{cription Drug Us}^{er Fee Act I}^Vⁱⁿ^ex^pl^oratⁱ^oⁿ^of^ben^e^fⁱ^t^s^of^Str^a^tegy⁽^R^E^M^{S [}^s^ee
^adv^e^rs^{e ev}^en^{t reportin}^g^;^below^{]) an}^{d th}^{e rev}ⁱ^ew^of
^acq^uⁱ^sitioⁿ^an^d^u^s^{e o}^f^saf^e^tyⁱⁿ^f^o^r^m^atioⁿⁱⁿ^clu^dⁱⁿ^g
^dat^a^bas^e^s^;^dev^e^l^{op g}^uⁱ^dan^c^e^adv^e^rs^{e ev}^en^{t reports}^.
^on^ph^arm^acoepidem^iologⁱ^c
^stu^d^{ies an}^d^oⁿ^clin^ical
^h^e^patoxⁱ^city^an^{d en}^rich^ed
ⁱ^{ki/CRS-RL33925}^tr^{ial d}^e^sigⁿ^s^{; an}^d^im^p^r^o^v^e
^g/w^com^m^uⁿⁱ^cation^betw^een
^s^.or^{OSE an}^d^OND.
^le^akⁱ^eⁿ^{ce an}^{d exper}^tⁱ^s^e
^://wiki^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at in}^B^e^ga^{n up}^gr^a^dⁱ^{ng t}^h^e^W^e^b^-^W^o^u^l^dⁿ^o^{t r}^e^q^u^ir^{e sy}^stem^atic^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^h^ttp^d^e^r^to^im^p^r^o^v^{e th}^{e g}^eⁿ^e^r^a^tioⁿ^o^fⁿ^e^w^saf^e^ty^acces^sⁱ^{ble A}^d^v^e^rs^{e Ev}^en^ts^an^d^scien^tif^{ic r}^e^vⁱ^ew^{, b}^u^t
^l^s^aⁿ^d^hy^p^o^t^he^se^s,^CD^E^R⁽^a⁾^c^o^nd^uc^t^a^Rep^o^r^{ting Sy}^stem⁽^A^E^R^S)^I^I^w^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^{e n}^e^w
^stem^{atic, scien}^tif^ic^review^{of the AE}^RS^to^ad^d^sigⁿ^a^{l d}^e^tectioⁿ^an^d^C^eⁿ^t^{er D}ⁱ^rect^{or i}^m^prov^e
^Advers^{e E}^v^{ent Reporting Sys}^t^em^]^trackⁱⁿ^g^tools^.^Im^plem^en^tin^g^p^o^s^tm^ar^k^e^{t su}^r^v^eillan^c^e
^st^e^m^{, (}^b⁾^id^en^tif^y^an^d^im^plem^{ent changes}^electronⁱ^{c s}^y^s^t^em^acros^s^p^r^o^g^r^a^m^s^an^d^activ^ities.
^e^y^f^actors^th^{at cou}^l^{d lead to a m}^o^re^C^D^ER^of^fⁱ^ces^{to track}
ⁱ^cien^{t s}^y^s^t^em^{, an}^{d (c) s}^y^s^t^em^atically^p^o^s^tm^ar^k^e^{t saf}^e^ty^issu^es.
^plem^ent^st^a^t^istⁱ^ca^l-^surv^eilla^{nce m}^e^t^h^o^d^s
^{a reg}^u^l^{ar an}^{d rou}^tin^{e bas}ⁱ^s^f^o^{r th}^e^If^PD^U^F^A^IV^propos^alⁱ^s
^tom^a^ted^ge^ne^r^a^tⁱ^o^{n o}^f^ne^w^sa^fe^t^y^si^gna^l^s^.^{accepted, w}^o^u^l^{d s}^eek^ou^ts^ide
^res^earch^org^aⁿⁱ^zation^s^to
^st^ud^y^ho^w^t^o^m^a^xi^mⁱ^z^e
^p^u^b^{lic h}^ealth^b^eⁿ^e^f^{its o}^f^th^e
^co^llectioⁿ^an^d^r^e^p^o^r^tin^g^o^f
^adv^e^rs^{e ev}^en^ts^ov^{er a}
^produ^ct’^s^lif^ecy^cle.

CRS-8
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at in}^W^o^ul^d^use^P^D^U^F^A^I^V^fund^s^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^{e n}^e^w^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^d^e^r^to^f^{acilitate th}^{e f}^o^r^m^u^l^atioⁿ^an^d^testin^g^t^o^acquⁱ^{re dat}^a^bas^e^s^an^{d h}ⁱ^re^C^eⁿ^t^{er Director con}^d^u^c^t
^dru^g^s^a^f^e^t^y^h^y^pot^h^e^s^e^s^,^C^D^ER^{(a) i}ⁿ^creas^e^s^t^af^f^{to u}^s^{e th}^em^{; con}^d^u^c^t^p^o^s^tm^ar^k^e^tin^g^su^r^v^eillan^ce,
^tram^u^r^{al an}^{d ex}^tram^u^r^{al prog}^ram^s^th^at^tar^g^eted^p^o^s^tm^ar^k^e^tin^g^u^sⁱⁿ^g^ris^k^-^b^en^ef^{it an}^aly^s^es^,
^{nd st}^udy^da^t^a^f^r^o^m^la^rg^e^su^r^v^eillan^{ce, stu}^d^y^d^r^u^g^-^adv^e^rs^{e ev}^en^{t reports}^{, an}^d
^t^o^m^a^t^e^{d hea}^l^t^h^ca^{re da}^t^a^ba^ses^{, an}^{d (b)}^clas^s^ef^f^ects^,^an^{d detect}^clin^{ical an}^{d obs}^erv^a^tion^a^l
^d^{e in}^th^es^{e prog}^ram^s^st^{udies o}ⁿ^drug^si^gna^l^s^.^stu^d^{ies. W}^o^u^l^d^r^e^q^u^ir^{e th}^e
^iliza^t^ioⁿ^pat^t^e^rn^s^an^d^ba^ck^g^r^o^undⁿ^e^w^C^eⁿ^t^{er to con}^t^{ract w}^ith
^f^o^{r adv}^e^rs^{e ev}^en^ts^ofⁱⁿ^teres^t^,^S^pon^s^o^riⁿ^g^pu^blⁱ^c^m^eetⁱⁿ^g^d^o^m^{estic an}^dⁱⁿ^terⁿ^atioⁿ^a^l
^{d (c) dev}^e^l^{op an}^{d i}^m^pl^em^en^t^acti^ve^{to ex}^{plore opportu}ⁿ^ities^f^o^r^patⁱ^eⁿ^t^dat^a^bas^e^s^{(or requ}ⁱ^r^e
^eilla^nce^of^s^p^ecifⁱ^{c dru}^g^s^an^{d dis}^eas^es^as^lⁱⁿ^kⁱⁿ^g^pri^v^at^e-^an^{d pu}^blⁱ^c^-^t^h^{e dru}^g^s^pon^s^o^{r t}^o^{do s}^o^{) t}^o
^{a v}^a^riety^of^s^e^ttin^g^s^.^secto^r^“^p^o^s^tm^ar^k^e^tin^g^saf^e^ty^con^d^u^c^{t epidem}^iologⁱ^{c an}^d
^m^oⁿ^itorin^g^s^y^s^t^em^s^{to create}^o^t^he^r^o^b^s^e^r^va^tⁱ^o^na^l^st^udⁱ^e^s.
ⁱ^{ki/CRS-RL33925}^{a v}ⁱ^r^t^u^a^{l in}^teg^r^ated^,
^g/wⁱⁿ^ter^o^p^e^r^a^b^l^{e Natio}ⁿ^w^id^e
^s^.or^m^e^di^cal^produ^ct^s^a^f^e^t^y^ne^t^w^o^r^k.^”
^le^ak
^://wiki^W^o^ul^d^use^P^D^U^F^A^I^V^fund^s^t^o^dev^e^l^{op g}^uⁱ^dan^{ce on}
^h^ttp^c^o^nd^uc^tⁱⁿ^g
^ph^arm^acoepidem^iologⁱ^c
^st^udⁱ^e^{s usi}^{ng l}^a^r^g^e^he^a^l^t^h^c^a^r^e
^d^a^{ta sets; w}^o^u^l^d^h^o^ld^p^u^b^lic
^w^o^r^k^sh^o^p^to^id^en^tif^y^b^e^st
^practices^an^{d is}^s^u^{e g}^uⁱ^dan^c^e
^on^s^u^ch^practices^.
^Wou^l^{d dev}^e^l^{op g}^uⁱ^dan^{ce on}
^clin^{ical h}^e^p^a^to^xⁱ^city^an^d
^en^rⁱ^ch^ed^tr^{ial d}^e^sigⁿ^s^to
^s^u^pport^t^h^{e prev}^en^tⁱ^oⁿ^of
^s^a^f^e^t^y^probl^em^s^du^riⁿ^g^dru^g
^dev^e^l^opm^en^t^.

CRS-9
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^Cu^r^r^en^{t d}^a^ta-^s^h^a^rⁱⁿ^g
^activ^{ities in}^clu^d^{e ag}^r^eem^en^ts
^w^ith^th^{e A}^g^en^cy^f^o^r
^Health^{care R}^e^s^earch^an^d
^Qu^ality^an^d^th^{e Veter}^aⁿ^s
^Health^A^d^mⁱⁿⁱ^str^a^tioⁿ^,^an^d
^activ^{e m}^oⁿ^ito^rⁱⁿ^g^an^d
^an^aly^s^is^ofⁱⁿ^f^l^u^eⁿ^{za v}^accin^e
^sa^fe^ty^.
^D^e^ve^l^o^pⁱ^{ng (}^t^hr^o^{ugh t}^h^e
^cr^{itical p}^a^thⁱⁿ^itiativ^es)
^techⁿⁱ^qu^es^f^o^{r predictiv}^e
ⁱ^{ki/CRS-RL33925}^to^xⁱ^co^lo^g^y^{, id}^en^tif^yⁱⁿ^g
^g/w^dru^g^s^’^cardiov^as^cu^{lar ris}^k^,
^s^.or^prev^en^tin^g^dru^g^-ⁱⁿ^du^ced^liv^erⁱⁿ^j^u^r^y^{, u}^sⁱⁿ^gⁱⁿ^teg^r^ated
^le^akⁱⁿ^fo^r^m^a^tⁱ^o^n,^usi^{ng ne}^w^t^o^o^l^s
^://wiki^t^o^en^h^aⁿ^{ce bl}^{ood s}^a^f^e^t^y^{, an}^d^e^nha^ncⁱ^{ng t}^h^e^sa^fe^t^y^o^f^ge^ne
^h^ttp^th^erapy^.
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at th}^e^Sigⁿ^e^{d ag}^reem^en^{t w}^ith^th^e^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^of^{HHS, w}^o^rkⁱⁿ^g^w^ith^th^e^Veter^aⁿ^s^Health
^of^Veteran^s^A^f^f^a^irs^an^{d Def}^eⁿ^s^e,^A^d^mⁱⁿⁱ^str^a^tioⁿ^to^sh^ar^e
^e^l^{op a}^{public-private partners}^hip^w^ithⁱⁿ^f^o^r^m^atioⁿ^an^d^ex^p^e^r^tise
^g^s^pon^s^o^rs^{, pu}^blⁱ^c^an^{d pri}^v^at^{e i}ⁿ^s^u^rers^,^reg^a^rdiⁿ^g^m^e^di^cal^produ^ct
^r-^profⁱ^t^an^{d n}^o^t^-^f^o^r-^profⁱ^t^h^eal^t^h^care^s^a^f^e^ty^{, ef}^f^ectiv^en^es^s^,^an^d
^o^vⁱ^d^e^r^o^r^gaⁿⁱ^z^a^tⁱ^o^ns,^c^o^nsum^e^r^gr^o^u^p^s^,^aⁿ^d^pat^t^e^rn^s^of^u^s^e.
^{e p}^h^arm^aceu^{tical co}^m^p^an^{ies to}^p^r^io^ritize,
ⁿ^,^aⁿ^d^o^r^gaⁿⁱ^z^e^fundⁱ^{ng fo}^r^confirm^a^tory
^sa^f^e^t^y^a^{nd ef}^fⁱ^ca^cy^st^{udies o}^f^public
^l^t^h^im^po^rt^aⁿ^ce^.^Co^ngr^e^{ss sho}^u^ld
^pit^a^lize^th^{e p}^u^b^{lic sh}^ar^{e o}^f^th^{is p}^a^r^tⁿ^e^r^s^hⁱ^p^.

CRS-10
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at C}^D^ER^PD^U^F^A^IV^propos^al^Wou^l^{d s}^e^t^procedu^r^{e t}^o^Wou^l^{d requ}ⁱ^r^{e a s}^pon^s^o^{r t}^o^N^o^provⁱ^sⁱ^oⁿ^.

^s^u^{re th}^{e perf}^orm^aⁿ^{ce of}^ti^m^e^l^y^an^dⁱⁿ^clu^d^es^w^o^rk^tow^a^rd^r^e^q^uⁱ^r^e^rⁱ^{sk m}^a^na^ge^m^e^nt^s^u^bmⁱ^t^{a propos}^{ed R}ⁱ^s^k
^if^ica^lly^v^a^{lid ev}^a^l^ua^tⁱ^oⁿ^s^(w^h^e^t^h^erⁱ^d^eⁿ^tⁱ^f^yⁱ^{ng r}ⁱ^{sk m}^a^na^ge^m^e^nt^activ^{ities w}^h^en^d^eem^ed^Ev^alu^a^tioⁿ^an^d^Mitig^atioⁿ
^{e i}ⁿ^t^e^rn^al^l^y^{or by}ⁱⁿ^du^s^t^ry^s^pon^s^o^rs^{) of}^to^o^l^{s; a}^sse^ssm^eⁿ^{t o}^f^se^le^c^t^e^dⁿ^eces^s^a^ry^an^{d w}^o^u^l^{d requ}ⁱ^r^e^Str^a^tegy⁽^R^E^M^S)^{as p}^a^r^t^o^f
^Minⁱ^mⁱ^zatioⁿ^A^c^tioⁿ^P^l^an^{s (}^R^isk^M^A^P^s)^.^Risk^Minⁱ^mⁱ^zatioⁿ^A^c^tioⁿ^actioⁿ^to^en^su^r^e^f^o^llo^w^-^u^p^{its ap}^p^licatioⁿ^f^o^r^d^r^u^g
^P^l^aⁿ^s,^rⁱ^{sk m}^a^na^ge^m^e^nt^aⁿ^d^an^{d com}^p^l^e^tⁱ^oⁿ^of^s^pon^s^o^r^approv^al^{or bi}^ol^ogⁱ^c^s
^rⁱ^{sk c}^o^m^m^uni^c^a^tⁱ^o^{n t}^o^o^l^s;^requ^irem^en^ts^.^lic^eⁿ^sur^e^.^RE^M^S^m^u^st
^a^nnua^l^sy^st^e^m^a^tⁱ^c^r^e^vi^e^w^aⁿ^dⁱⁿ^clu^d^{e lab}^e^lin^g^,^r^e^p^o^r^{ts o}^f
^pu^blⁱ^c^di^s^c^u^s^sⁱ^on^of^s^e^l^ect^ed^stu^d^{ies an}^d^su^r^v^eillan^{ce d}^a^ta,
^prog^ram^s^an^{d t}^ool^s^an^d^an^{d a ph}^arm^acovⁱ^g^ilan^c^e
^di^s^s^e^mⁱⁿ^a^tⁱ^oⁿ^of^report^s^;^an^d^s^t^atem^en^{t. B}^a^s^e^{d on}^th^e
^pu^blⁱ^c^w^o^rk^s^h^ops^t^o^g^e^t^es^tⁱ^m^at^{ed n}^u^m^{ber of}^peopl^e
^p^r^io^r^itizatioⁿ^g^uⁱ^d^aⁿ^{ce f}^r^o^m^w^h^o^w^o^ul^d^t^a^ke^t^h^e^d^r^ug,
ⁱ^{ki/CRS-RL33925}ⁱⁿ^du^s^t^ry^an^{d ot}^h^e^rs^.^dis^eas^{e s}^e^riou^sⁿ^es^s^,^ex^pected
^g/w^d^u^r^a^tioⁿ^o^f^tr^eatm^eⁿ^t^{, an}^d
^s^.or^av^ailab^ility^o^f^o^t^h^e^r^tr^eatm^eⁿ^t^{s, th}^e
^le^ak^ph^arm^acovⁱ^g^ilan^{ce s}^t^atem^en^t
^://wiki^w^o^u^l^{d prov}^{ide an}^as^s^e^s^s^m^en^t^of^adequ^acy^of^R^E^MS
^h^ttp^activ^{ities to}^{assess ser}ⁱ^o^u^s
^rⁱ^sk^{s, to}^id^en^tif^y^uⁿ^e^x^p^ected
^se^rⁱ^o^u^{s r}ⁱ^{sks o}^f^the^d^r^{ug a}ⁿ^d
^w^h^e^t^he^r^st^udⁱ^e^{s a}^r^e
^ne^c^e^ssa^r^y^,^aⁿ^d^,^{if stud}^ie^{s a}^r^e
^ne^c^e^ssa^r^y^,^to^d^e^sc^rⁱ^b^e^w^h^a^t
^o^b^s^er^v^a^tioⁿ^a^{l an}^d^clin^ical
^s^t^u^d^ies^{are requ}^ired.

CRS-11
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^If^th^{e Secretary}^w^e^{re to}
^d^e^ter^mⁱⁿ^{e it n}^ecessar^y^{, th}^e
^Secretary^cou^l^{d requ}^{ire th}^at
^th^{e R}^E^{MS in}^clu^d^{e a s}^pon^s^o^r-
^dev^e^l^{oped Medi}^catⁱ^oⁿ^G^uⁱ^d^e
^o^r^p^a^tien^t^p^ack^ag^{e in}^ser^{t; a}
^plan^{to com}^m^uⁿⁱ^{cate w}^ith
^h^ealth^{care prov}^iders^,
^en^cou^r^agⁱⁿ^g^im^plem^en^tation
^o^f^r^e^l^e^va^nt^RE^M^S
^com^pon^en^t^s^;^pos^t^-^approv^al
^o^b^s^e^r^va^tⁱ^o^na^l^st^udⁱ^e^{s (}^t^ha^t
^th^{e applican}^{t or th}^{e Secretary}
ⁱ^{ki/CRS-RL33925}^cou^l^{d con}^d^u^c^{t) or clin}^ical
^g/w^tr^{ials, w}^ith^tar^g^{et sch}^e^d^u^les
^s^.or^f^o^r^co^m^p^letioⁿ^an^d^reportⁱⁿ^g^;^an^{d res}^t^ri^ctⁱ^oⁿ^s^on
^le^ak^a^d^ve^r^tⁱ^sⁱ^ng.
^://wiki^W^o^u^l^{d requ}^{ire an}^as^s^e^s^s^m^en^t
^h^ttp^of^an^approv^{ed R}^E^MS
^a^nnua^l^l^y^fo^r^t^h^e^fi^r^s^t^t^h^r^e^e
^y^ear^{s af}^terⁱⁿ^itial
^ap^p^r^o^v^al/licen^su^r^e^an^d^th^en
^a^t^a^fr^e^q^ue^nc^y⁽ⁱ^nc^l^u^dⁱ^ng
ⁿ^oⁿ^e^{) as}^s^p^ecifⁱ^{ed in}^th^e
^RE^M^S^.

CRS-12
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at C}^D^ER^H^e^l^d^w^o^rk^s^h^{op on}^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^{e n}^e^w^Wou^l^{d requ}ⁱ^r^{e R}^E^MS^t^o^N^o^provⁱ^sⁱ^oⁿ^.

^e^l^{op an}^{d con}^tⁱⁿ^u^a^l^l^yⁱ^m^prov^{e a s}^y^s^t^em^atⁱ^c^q^u^an^titativ^{e b}^eⁿ^e^f^it-^rⁱ^sk^Ce^nt^e^r^c^o^nd^uc^t^aⁿ^d^use^rⁱ^sk-ⁱⁿ^clu^d^{e con}^s^ideration^of
^t^o^ris^k^{-benefit analys}^is^fo^r^use^as^s^e^s^s^m^en^{t; ex}^plorin^g^u^s^{e of}^b^eⁿ^e^f^{it an}^aly^s^{is, b}^u^{t w}^o^u^l^d^sc^o^p^e^o^f^use^,^se^rⁱ^o^u^sne^{ss o}^f
^o^ugho^ut^t^h^e^FD^Aⁱⁿ^t^h^e^p^reap^p^r^oval^an^d^bes^t^practices^an^dⁿ^o^{t r}^e^q^u^ir^{e th}^{at FDA}^d^e^v^e^lo^p^th^{e d}ⁱ^{sease o}^r^coⁿ^d^itioⁿ^th^at
^s^t-ap^p^r^oval^settin^g^s^.^id^en^tif^icatioⁿ^an^d^testin^g^o^f^an^{d im}^prov^{e a s}^y^s^t^em^atic^th^{e d}^r^u^g^{is u}^s^ed^to^tr^{eat o}^r
^q^u^an^titativ^{e to}^o^l^{s; h}^a^v^e^approach^.^p^r^e^v^eⁿ^t,^se^rⁱ^o^u^sne^{ss o}^f
ⁱⁿ^trodu^{ced train}ⁱⁿ^g^cou^r^s^e^s^adv^e^rs^{e ev}^en^ts^{, an}^{d oth}^e^r
^f^o^{r m}^e^{dical rev}ⁱ^ew^ers^.^av^{ailable treatm}^eⁿ^t^.
^C^r^{eated g}^r^ou^{p of}ⁱⁿ^tern^al^W^h^en^con^cern^e^{d abou}^{t a}
^ex^pert^s^t^o^dev^e^l^o^p^se^rⁱ^o^u^{s r}ⁱ^{sk tha}^t^m^a^y^b^e
^q^u^an^titativ^{e m}^e^th^o^d^s^f^o^r^r^e^lated^to^th^{e p}^h^ar^m^aco^lo^gⁱ^c
^saf^e^ty^ev^alu^a^tioⁿ^,^d^e^v^e^lo^p^clas^s^of^{a dru}^g^,^th^{e Secretary}
ⁱ^{ki/CRS-RL33925}^an^{d di}^s^s^e^mⁱⁿ^a^t^e^bes^t^cou^l^{d def}^e^{r a R}^E^MS
^g/w^practices^of^s^a^f^e^ty^revⁱ^ew^s^a^sse^ssm^eⁿ^t^w^hⁱ^l^e^c^o^nveⁿⁱ^ng
^s^.or^du^riⁿ^g^produ^ct^dev^e^l^opm^en^t^,^an^d^to^p^r^o^v^id^{e co}ⁿ^s^isten^c^y^m^eetin^g^s^o^f^th^{e p}^u^b^lic,^advⁱ^s^o^ry^com^m^ittees^{, or}
^le^ak^a^c^r^o^{ss r}^e^vie^w^dⁱ^visioⁿ^s.^ex^pert^pan^e^l^s^t^o^di^s^c^u^s^s
^://wiki^Iⁿ^itiated^cr^{itical p}^a^th^p^o^ssib^l^e^r^e^sp^oⁿ^se^{s to}^tha^t^con^cern^.
^h^ttpⁱⁿ^itiativ^{es [}^S^{ee r}^e^sp^oⁿ^{se to}
^recom^m^eⁿ^d^atⁱ^oⁿ^{4.2 abov}^e]^Secretary^m^a^y^coordin^a^te
^an^{d a pi}^l^o^t^prog^ram^t^o^tim^etab^{le to}^r^e^vⁱ^ew^ef^f^o^r^t^{s o}^f
^s^y^s^t^em^atically^revⁱ^ew^s^a^f^e^tyⁱⁿ^terⁿ^atioⁿ^a^{l m}^a^r^k^etin^g
^profⁱ^l^e^s^ofⁿ^e^w^m^o^l^ecu^l^a^r^au^th^o^r^ities.
^en^{tities (}^N^MEs)^[^S^{ee 5}^.⁴
^bel^o^w^]^.
^Estab^lish^e^d^p^r^o^g^r^a^m^w^ith^th^e
^Natioⁿ^a^{l T}^o^xⁱ^co^lo^g^y
^P^r^o^g^r^a^m^o^f^th^{e Natio}ⁿ^a^l
^Iⁿ^stitu^{te o}^f^En^vⁱ^r^oⁿ^m^en^tal
^Health^Scien^{ces to}^d^e^v^e^lo^p
^an^im^{al m}^o^d^e^{l to}^assess
^can^{cer ris}^k^as^s^o^{ciated w}^ith
^ge^ne^t^h^e^r^a^p^y^.

CRS-13
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^Iⁿ^itiativ^{e u}ⁿ^d^er^w^a^y^to
^st^r^e^ngt^he^{n t}^h^e^sa^fe^t^y
^ev^alu^a^tion^proces^s^,ⁱⁿ^clu^dⁱⁿ^g
^s^t^an^dardi^{zed m}^e^t^h^odol^ogⁱ^e^s^,
^t^r^aⁱⁿⁱ^{ng a}ⁿ^d^m^e^nt^o^rⁱ^ng,
^w^o^r^k^lo^ad^p^r^io^r^itizatioⁿ^,^an^d
^m^a^na^ge^m^e^nt^t^o^o^l^s.
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at C}^D^ER^[^S^e^e^r^e^sp^oⁿ^se^{s to}^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.
^erna^l^epidem^io^lo^gⁱ^{c a}ⁿ^d^recom^m^eⁿ^d^ation^s^{3.5 an}^d
^atics^capacityⁱⁿ^{order t}^oⁱ^m^prov^{e t}^h^e^{4.2 abov}^e.]
^t^m^ark^e^t^as^s^e^s^s^m^en^t^of^dru^g^s^.
ⁱ^{ki/CRS-RL33925}^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at th}^e^m^mⁱ^s^sⁱ^on^{er of}^F^D^A^dem^oⁿ^s^t^r^at^e
^g/w^m^m^itm^en^{t to}^b^u^ildⁱⁿ^g^th^{e ag}^en^cy^’^s
^s^.or^ien^tif^{ic res}^earch^capacity^by^:
^le^ak
^ppoiⁿ^tⁱⁿ^g^a^Chief^Scient^istⁱⁿ^th^{e o}^f^fⁱ^ce^C^o^m^mⁱ^s^sⁱ^on^{er propos}^ed^{No com}^p^{arable prov}^is^ion^,^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.
^://wiki^th^{e Co}^m^mⁱ^ssioⁿ^er^w^ith^r^e^sp^oⁿ^sib^ility^f^o^r^creation^of^th^{e Of}^fⁱ^{ce of}^th^e^b^u^{t th}^{e b}^{ill w}^o^u^l^d^cr^{eate a}
^h^ttp^e^r^se^eⁱ^ng,^c^o^o^r^dⁱ^na^tⁱ^ng,^aⁿ^d^eⁿ^surⁱ^{ng t}^h^e^C^h^ief^{Medical Of}^fⁱ^{cer to}^se^p^a^r^a^te^Ce^nte^r^fo^r
^ality^an^d^r^e^g^u^l^ato^r^y^f^o^cu^{s o}^f^th^{e ag}^en^cy^’^s^o^v^er^{see FDA}^scien^tif^ic^P^o^s^t^m^a^rk^{et Ev}^alu^a^tion^an^d
^u^r^{al res}^earch^prog^ram^s^.^operatⁱ^oⁿ^s^.^R^e^s^earch^f^o^{r Dru}^g^s^an^d
^Bⁱ^o^l^o^gⁱ^c^{s (}^t^he^ne^w^Ce^nt^e^r⁾
^an^d^th^{e p}^o^s^itioⁿ^o^f^Dir^ecto^r
^o^f^t^h^e^ne^w^Ce^nt^e^r^.
^D^e^si^gna^tⁱ^{ng t}^h^e^FD^A^’^s^{Science B}^o^a^r^d^as^As^k^e^d^t^h^e^F^D^{A S}^cⁱ^eⁿ^c^e^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.
^tram^u^r^{al adv}ⁱ^s^o^ry^com^m^{ittee to th}^e^B^o^ar^d^to^r^e^vⁱ^ew^scien^tif^ic
^ief^Scien^tist.ⁿ^eed^{s an}^d^activ^{ities acr}^o^s^s
^FD^A^;^e^nga^gi^{ng e}^x^t^e^rⁿ^a^l
^c^o^nsul^t^a^nt^{s t}^o^he^l^p^d^e^ve^l^o^p
^c^o^m^p^r^e^he^nsi^v^e^st^r^a^t^e^gy^t^o
ⁱ^m^prov^{e org}^aⁿⁱ^zatⁱ^oⁿ^a^l
^cu^ltu^r^e^.
ⁿ^c^l^udⁱ^ng^res^{earch capacity}ⁱⁿ^th^e^N^o^t^addres^s^e^d.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^en^cy^’^s^mⁱ^s^sⁱ^on^s^t^atem^en^t.

CRS-14
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^ppl^yⁱⁿ^g^res^o^u^r^ces^t^o^suppo^rt^int^r^a^m^ura^l^N^o^t^addres^s^e^d.^Wou^l^{d requ}ⁱ^r^{e t}^h^at^t^h^{e n}^e^w^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.
^earch^ap^p^r^o^v^ed^b^y^th^{e Ch}^ief^Scien^tist.^Ce^nt^e^r^c^o^nd^uc^t^p^o^s^t^m^a^r^ke^t
^rⁱ^{sk a}^sse^ssm^eⁿ^ts.
^s^u^rin^g^th^at^a^d^equa^t^e^f^unding^t^o^s^u^pport^N^o^t^addres^s^e^d.^Wou^l^{d au}^t^h^ori^z^e^W^o^ul^d^a^l^l^o^w^fo^r^use^r^-fe^e^N^o^provⁱ^sⁱ^oⁿ^.
^tram^u^r^{al res}^earch^prog^ram^is^requ^es^ted^appropri^a^tⁱ^oⁿ^s^[s^{ee bel}^o^w^]^.^r^e^ve^nue^t^o^b^e^use^d^fo^r
^h^e^a^g^eⁿ^c^y^{’s a}^nnua^l^b^u^d^g^e^t^r^e^q^u^e^s^t^t^o^{REMS ev}^alu^a^tioⁿ^activ^ities.
^ngr^e^ss.
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at FDA}^Coⁿ^d^u^c^tin^g^p^ilo^{t p}^r^o^g^r^a^m^to^{No com}^p^{arable prov}^is^ion^,^Secretary^m^a^y^con^v^eⁿ^e^an^N^o^provⁱ^sⁱ^oⁿ^.
^veⁱ^t^s^advis^o^{ry com}^mⁱ^ttees^review^all^revⁱ^ewⁿ^e^w^m^o^lecu^lar^b^u^{t th}^{e b}^{ill w}^o^u^l^d^r^e^q^u^ir^e^advⁱ^s^o^ry^com^m^{ittee m}^eetin^g
^E^s^[new^m^o^{lecular entities}^]^eith^er^p^r^io^r^en^{tities [}^S^{ee r}^e^sp^oⁿ^{se to}^preapprov^al^revⁱ^ew^by^t^h^e^{to rev}ⁱ^ew^s^a^f^e^ty^con^cern^s^or
^al^{or s}^oon^af^t^e^{r approv}^al^{to ad}^vi^s^e^recom^m^eⁿ^d^atⁱ^oⁿ^{5.4 bel}^o^w^]^.^ne^w^Ce^nt^e^r^,^aⁿ^d^w^o^ul^d^{a R}^E^{MS f}^o^{r a dru}^g^{or a clas}^s
^s^{of ens}^u^{ring drug s}^a^{fety and}^r^e^q^u^ir^{e ad}^vⁱ^so^r^y^co^m^m^ittee^of^dru^g^s^.
ⁱ^{ki/CRS-RL33925}^a^{naging drug ris}^k^s^.^coⁿ^s^u^ltatioⁿ^b^e^f^o^r^e^th^{e n}^e^w^C^eⁿ^t^{er Director m}^a^k^e^s^a
^g/w^saf^e^ty^d^e^ter^mⁱⁿ^atioⁿ^o^r
^s^.or^orders^{a correctiv}^{e action}^.
^le^ak
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at all}^W^{ill in}^cr^{ease (}^t^o^th^{e ex}^ten^t^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^Wou^l^{d requ}ⁱ^r^{e H}^H^S
^://wiki^dru^g^produ^{ct adv}ⁱ^s^o^ry^com^m^ittees^{, an}^d^f^easib^le)^Secretary^{to allow}^FDA^s^t^af^f
^h^ttp^y^oth^e^{r peer rev}ⁱ^ew^ef^f^o^{rt s}^u^ch^as^ph^arm^acoepidem^iolog^y^to^p^r^esen^{t in}^f^o^r^m^atioⁿ^to^an
ⁿ^tⁱ^oⁿ^e^{d abov}^{e f}^o^{r C}^D^ER^-^r^evⁱ^e^w^e^{d produ}^ct^ex^pert^s^s^u^pport^t^o^advⁱ^s^o^ry^advⁱ^s^o^ry^com^m^{ittee if}^s^t^af^f^is
^f^e^ty^{, in}^clu^d^{e a}^p^h^a^rm^acoepⁱ^d^e^mⁱ^ol^ogi^s^t^or^com^m^ittees^.^w^o^rkⁱⁿ^g^on^{a t}^opi^{c t}^h^e
ⁱⁿ^dⁱ^vⁱ^d^u^{al w}^ith^co^m^p^ar^ab^{le p}^u^b^{lic h}^ealth^com^m^{ittee is}^con^s^iderin^g^.
^p^e^r^{tise in}^stu^d^yⁱⁿ^g^th^{e saf}^e^ty^o^f^m^e^dⁱ^cal
^ct^s^.
^T^h^{e com}^m^{ittee recom}^m^eⁿ^d^s^FDA^W^{ill issu}^{e n}^e^w^g^uⁱ^d^aⁿ^{ces to}^No^p^r^o^v^isioⁿ^.^No^p^r^o^v^isioⁿⁱⁿ^T^{itle I}^;^N^o^provⁱ^sⁱ^oⁿ^.

^lish^{a r}^e^q^u^ir^em^en^{t th}^{at a su}^b^s^tan^tial^addres^s^th^{e g}^r^an^tin^g^an^d^r^e^lated^p^r^o^v^isioⁿ^s^ar^{e in}^T^itle
^j^o^rity^of^th^{e m}^e^m^b^ers^of^each^advⁱ^s^o^ry^dⁱ^sclo^su^r^e^o^f^coⁿ^f^lict-^o^f^-^I^V⁽^“^Coⁿ^f^{licts o}^f^Iⁿ^ter^e^st”)^.
^m^{ittee be}^{free of s}ⁱ^{gnificant financial}ⁱⁿ^ter^e^{st w}^a^iv^er^{s f}^o^r^ad^vⁱ^so^r^y
^vol^vem^eⁿ^t^wⁱ^th^com^p^anⁱ^e^s^w^h^o^s^{e in}^ter^e^sts^com^m^{ittee m}^e^m^b^ers^,^an^{d to}
^y^{be af}^f^{ected by}^th^{e com}^m^ittee’^s^im^prov^{e th}^{e releas}^{e of}
^lib^er^atioⁿ^s^.^advⁱ^s^o^ry^com^m^{ittee brief}ⁱⁿ^g
^m^a^terⁱ^{als to}^th^{e p}^u^b^{lic. W}^ill
^m^a^k^e^ad^vⁱ^so^r^y^co^m^m^ittee
^m^e^m^b^{er recru}^itm^en^{t m}^o^re
^tr^an^sp^ar^en^{t b}^y^issuⁱⁿ^g^{lists o}^f
^v^acan^cies^.

CRS-15
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^o^en^s^u^{re t}^h^at^t^r^ia^{l reg}^ist^r^a^t^ioⁿ^is^N^o^t^di^rect^{ed t}^o^F^D^A^.^[N^ot^e:^S^eⁿ^a^t^o^rs^D^{odd an}^{d G}^r^as^s^l^eyⁱⁿ^t^r^odu^{ced a s}^e^parat^e^bi^l^l^N^o^provⁱ^sⁱ^oⁿ^.
ⁿ^d^atory^,^s^y^s^t^em^{atic, s}^t^an^{dardized, an}^d^(S^{. 467) t}^h^at^addres^s^e^s^t^h^{e i}^s^s^u^es^of^clⁱⁿⁱ^cal^t^rⁱ^a^l^regⁱ^s^t^ratⁱ^oⁿ
^m^p^{lete, an}^d^th^{at th}^{e r}^e^gⁱ^str^a^tioⁿ^{site is ab}^le^an^d^r^e^su^{lts d}^a^tab^a^{ses. T}^h^{e co}^m^p^ar^isoⁿ^o^f^th^{at b}^{ill to}^T^{itle I}^I^I
^m^{odate th}^{e reportin}^g^of^{trial res}^u^lts^,^of^S^.^{484 an}^{d t}^h^{e IO}^{M report}^recom^m^eⁿ^d^atⁱ^oⁿ^s^appearsⁱⁿ^a
^m^{ittee recom}^m^eⁿ^d^s^th^{at C}^oⁿ^g^r^es^s^s^e^parat^e^C^R^S^produ^ct^:^C^R^S^R^e^port^R^L^32832,^Clin^ica^l^Tria^ls
^u^ir^{e in}^d^u^str^y^sp^oⁿ^so^r^s^to^r^e^gⁱ^sterⁱⁿ^a^Repor^tⁱ^{ng and Publ}ⁱ^c^atⁱ^oⁿ^{, b}^y^Erⁱⁿ^{D. W}^illiam^s^.]
^ely^m^aⁿⁿ^e^{r at}^clin^ica^ltria^ls.g^o^v^{, at a}
ⁿⁱ^mu^m,^al^l^Ph^as^{e 2 th}^rou^g^h^{4 cl}ⁱⁿⁱ^c^al
^ls^{, w}^h^erev^{er th}^ey^m^a^y^h^a^v^e^been
^nd^uc^t^e^d^,ⁱ^f^d^a^{ta from}^th^{e tri}^a^l^s^are
^e^{nded t}^o^{be subm}^it^t^e^{d t}^o^t^h^{e F}^{DA a}^s
^{rt o}^f^aⁿ^{NDA [new}^drug^a^pplica^t^io^n],
^enta^{l new}^drug
^t^io^n]^{, o}^r^t^o^f^u^lf^{ill a}^po^st^m^a^rk^et
ⁱ^{ki/CRS-RL33925}^mⁱ^tm^ent^{. T}^h^{e com}^m^{ittee f}^u^rth^e^r^m^m^eⁿ^d^{s th}^{at th}^{is r}^e^q^u^ir^em^en^{t in}^clu^d^{e th}^e
^g/w^s^tⁱⁿ^{g of a s}^t^ru^ctu^{red field s}^u^m^m^a^{ry of}
^s^.or^a^{fety res}^ults^o^f^th^{e stu}^d^ies.
^le^ak
^T^h^{e com}^m^{ittee recom}^m^eⁿ^d^s^th^{at FDA}^{Not accepted.}^W^o^u^l^{d requ}^{ire th}^{at FDA}^pos^t^Wou^l^{d requ}ⁱ^r^{e t}^h^at^F^D^A^pos^t^W^o^u^l^d^r^e^q^u^ir^{e, w}^ithⁱⁿ²⁴
^://wiki^{st a}^{ll NDA rev}^iew^pa^ck^a^g^e^{s o}ⁿ^the^{all stu}^d^{ies r}^e^q^u^ir^ed^uⁿ^d^er^th^e^al^l^approv^{ed prof}^es^sⁱ^on^al^h^o^u^r^s^of^approv^al^{, t}^h^at^t^h^e
^h^ttp^c^y’s^w^e^b^sⁱ^t^e^.^preapprov^al^an^d^l^a^belⁱⁿ^g^an^{d an}^y^requⁱ^r^ed^Secretary^pu^blis^h^{a s}^u^m^m^a^ry
^pos^t^a^pprov^al^requⁱ^r^em^en^t^s^of^p^a^tien^t^lab^e^lin^gⁱⁿ^a^statem^en^{t o}^f^th^{e scien}^tif^ic
^th^{is sectio}ⁿ^.^s^earch^{able electron}ⁱ^c^basⁱ^s^f^o^{r t}^h^{e approv}^al^an^d
^reposⁱ^t^o^ry^.^h^o^w^th^{e decis}ⁱ^on^balan^ced
^rⁱ^{sks a}ⁿ^d^b^e^ne^fits.^T^h^e
^s^t^atem^en^{t m}^u^s^tⁱⁿ^clu^d^{e a}
^d^e^sc^rⁱ^p^tⁱ^o^{n o}^f^c^o^nt^r^o^ve^r^sⁱ^e^s
^an^{d di}^f^f^e^ren^ces^of^opiⁿⁱ^on
^w^ithⁱⁿ^FDA^an^d^th^eir
^res^o^lu^tion^s^{, an}^{d in}^clu^d^{e an}^y
^statem^en^{t su}^b^m^itted^f^o^r^th^e
^sum^m^a^r^y^b^y^invo^lve^d^sta^ff.

CRS-16
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^{e com}^m^{ittee recom}^m^eⁿ^d^s^th^{at C}^B^ER^Decisioⁿ^{s to}^p^u^b^licly^Wou^l^{d requ}ⁱ^r^{e t}^h^at^F^D^A^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^{e d}^r^u^g^Wou^l^{d requ}ⁱ^r^{e bi}^enⁿⁱ^al
ⁱ^ew^team^s^reg^u^l^arly^an^{d s}^y^s^t^em^atically^dⁱ^sc^lo^se^a^sse^ssm^eⁿ^{ts o}^f^p^u^b^lishⁱⁿ^th^{e Fed}^e^r^a^l^sp^oⁿ^so^r^sub^m^{it RE}^M^S^report^s^on^approv^ed
^t^m^a^rk^{et s}^t^{udy res}^ults^an^d^p^o^s^tm^ar^k^e^tin^g^saf^e^ty^stu^d^ies^R^e^gⁱ^s^t^{er an}^{d pos}^t^on^t^h^e^a^sse^ssm^eⁿ^t^s^a^t^l^e^a^s^t^a^nnua^l^l^y^applⁱ^catⁱ^oⁿ^s^s^u^pport^e^{d by}
^a^k^e^public^theⁱ^r^a^sse^ssm^eⁿ^{t o}^f^the^m^u^s^t^{be m}^a^{de on}^{a cas}^e-^by^-^Iⁿ^terⁿ^{et d}^r^u^g^saf^e^ty^an^d^f^o^{r th}^{e th}^{ree y}^ears^af^ter^noⁿⁱ^nfe^rⁱ^o^rⁱ^t^y^st^udⁱ^e^s,^aⁿ^d
ⁿⁱ^fⁱ^can^{ce o}^f^th^{e r}^e^su^{lts w}^ith^r^e^g^a^r^d^to^th^e^cas^{e bas}ⁱ^s^.^ef^f^ectiv^en^{ess in}^f^o^r^m^atioⁿ^.^ap^p^r^o^v^al/licen^su^r^e^{; af}^ter^th^at^bⁱ^a^nnua^l^r^e^p^o^r^t^s^r^e^ga^r^dⁱⁿ^g
^r^atioⁿ^o^f^rⁱ^sk^an^d^b^eⁿ^e^f^{it in}^f^o^r^m^atioⁿ^.^{at in}^creas^{ed or redu}^ced^p^o^s^tm^ar^k^e^{t stu}^d^ies.
^W^{ill p}^u^b^lishⁿ^e^w^s^letter^oⁿ⁽ⁱ^nc^l^u^dⁱ^{ng no}^ne⁾^fr^e^q^ue^nc^y
^FDA^w^e^b^s^{ite, su}^m^m^a^rⁱ^zin^g^as^th^{e Secretary}^determⁱⁿ^es^Wou^l^{d proh}ⁱ^bⁱ^t^di^rectⁱⁿ^g
^res^u^l^t^s^an^{d m}^e^t^h^ods^of^to^b^e^ne^c^e^ssa^r^y^.^W^o^uld^se^t^F^D^A^s^t^af^f^t^o^di^s^t^ort^or
^pos^tm^ark^e^{t rev}ⁱ^ew^s^,^an^d^tim^{e lim}^{its f}^o^r^th^{e Secr}^etar^y^sup^p^r^e^{ss sc}^ie^ntific^r^e^se^a^r^c^h^,
^p^r^o^v^idⁱⁿ^gⁱⁿ^f^o^r^m^atioⁿ^oⁿ^to^{act o}ⁿⁱⁿ^{itial REMS an}^d^an^al^y^sⁱ^s^{, opi}ⁿⁱ^on^{, or}
^em^ergⁱⁿ^g^s^a^f^e^ty^is^s^u^es^an^d^m^odi^fⁱ^catⁱ^oⁿ^requ^es^t^s^.^r^eco^m^m^eⁿ^d^atioⁿ^s^o^r^to
^on^recen^tly^approv^ed^w^ilf^u^lly^dⁱ^sclo^{se scien}^tif^ic
^produ^ct^s^.^A^dⁱ^sp^u^t^{e r}^e^so^lu^tioⁿ^p^r^o^cessⁱⁿ^f^o^r^m^atioⁿ^th^{at is f}^a^lse,
ⁱ^{ki/CRS-RL33925}^W^{ill issu}^{e f}ⁱⁿ^a^{l g}^uⁱ^d^aⁿ^{ce o}ⁿ^w^o^u^l^{d in}^clu^d^{e tim}^ef^ram^e^s^,^an^{d in}^v^o^lv^{e rev}ⁱ^ew^by^an^d^mⁱ^sleadⁱⁿ^g^,^o^rⁱⁿ^co^m^p^lete.^Wou^l^{d prov}ⁱ^d^{e f}^o^r
^g/w^c^o^m^m^uni^c^a^tⁱ^{ng i}^m^p^o^r^t^a^nt^r^eco^m^m^eⁿ^d^atioⁿ^s^o^f^th^e^dⁱ^scip^lin^ar^y^actioⁿ^s^an^d
^s^.or^d^r^u^g^saf^e^tyⁱⁿ^f^o^r^m^atioⁿ^to^D^r^{ug Sa}^fe^t^y^O^v^e^r^si^ght^B^o^a^r^d^w^o^ul^d^r^e^q^uⁱ^r^e^a^nnua^l
^le^ak^h^ealth^{care prof}^es^sⁱ^on^als^,⁽^w^ith^ad^d^e^d^ex^p^e^r^{tise, if}^In^s^p^ect^{or G}^eⁿ^e^ral^report^s^.
^://wiki^patⁱ^eⁿ^t^s^,^an^{d ot}^h^e^r^c^o^nsum^e^r^s.ⁿ^eces^s^a^ry^{, f}^r^om^th^{e FDA}^of^fⁱ^ces^of^P^e^diatrics^,^Wou^l^{d al}^s^o^provⁱ^d^e^w^hⁱ^s^t^l^e^bl^ow^{er prot}^ectⁱ^oⁿ
^h^ttp^W^o^m^eⁿ^’^s^Health^{, an}^{d R}^a^re⁽^w^ith^p^r^o^v^isioⁿ^s^f^o^r
^Dis^eas^es^).^en^f^o^r^cem^en^{t an}^d^p^eⁿ^a^lities)
^an^d^th^{e r}ⁱ^g^h^t^to^p^u^b^lish^.

CRS-17
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^u^la^tioⁿ
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^at^{Not directed to FDA}^.^W^o^u^l^{d au}^th^{orize FDA}^to^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^{e d}^r^u^g^W^o^u^l^{d au}^th^{orize th}^e
ⁿ^g^r^es^s^en^s^u^{re t}^h^at^t^h^{e F}^{ood an}^{d D}^r^u^g^r^e^q^u^ir^{e saf}^e^ty^an^d^sp^oⁿ^so^r^sub^m^{it a}^RE^M^S^fo^r^Secretary^,^af^{ter prov}^idin^g
^mⁱⁿⁱ^st^r^a^tⁱ^o^{n ha}^s^t^h^{e a}^b^ilit^y^t^o^require^e^ffe^c^tiveⁿ^e^{ss stud}^ie^s,^eachⁿ^e^w^dru^g^an^{d biolog}^ic,^p^u^b^{lic n}^o^{tice, to}^o^r^d^e^r^th^e
^h^po^st^m^a^r^k^e^t^ing^rⁱ^sk^a^sse^ssm^eⁿ^t^aⁿ^dⁱⁿ^clu^dⁱⁿ^gⁱⁿ^co^m^p^ar^isoⁿ^to^fo^r^a^ge^ne^rⁱ^c^d^r^{ug (}^a^l^l^sp^oⁿ^so^r^to^coⁿ^d^u^c^{t stu}^d^{ies to}
^k^m^aⁿ^agem^eⁿ^t^p^r^ogram^s^as^{are n}^eed^ed^o^t^he^r^d^r^ugs/^bⁱ^o^l^o^gi^c^s^,ⁱⁿ^f^o^rm^ation^ex^cept^a^d^d^r^e^{ss sa}^fe^ty^o^r
^o^{nitor and ens}^u^{re s}^a^{fe us}^e^of^dru^g^accordin^g^{to FDA}^-^s^p^ecifⁱ^ed^p^o^s^tap^p^r^o^v^{al clin}^{ical tr}^ials)^,^ef^f^ectiv^en^es^s^is^s^u^es
^o^d^u^{cts. T}^h^{ese co}ⁿ^d^itioⁿ^s^m^a^y^b^e^im^p^o^s^ed^tim^etab^{le an}^d^ter^m^{s, if}^{, at}^f^o^r^{a n}^e^wⁱⁿ^dⁱ^catioⁿ⁽^e^ith^er^id^en^tif^ied^af^ter
^h^b^e^{fore an}^d^{after ap}^p^r^oval^of^{a n}^e^w^an^y^tim^{e, th}^{e n}^e^w^C^eⁿ^t^er^f^o^{r a dru}^g^w^ith^{a cu}^rren^t^ap^p^r^o^v^al/licen^su^r^e^.
^lecu^lar^en^tity^{, n}^e^wⁱⁿ^dⁱ^catioⁿ^,^o^rⁿ^e^w^Dir^ecto^r^d^e^ter^mⁱⁿ^{es th}^e^R^E^MS^{or a dru}^g^wⁱ^t^h^ou^t^a
^ag^{e, as}^w^e^{ll as}^{after identifica}^ti^on^{of n}^e^wⁿ^eed.^R^E^{MS w}^h^en^{a pres}^cription^is
ⁿ^t^r^aⁱⁿ^dⁱ^catioⁿ^s^o^r^p^a^tterⁿ^{s o}^f^ad^v^e^r^s^e^r^e^q^u^ir^ed^f^o^r^{its d}ⁱ^sp^en^sin^g⁾^,
^en^{ts. T}^h^{e lim}^itatioⁿ^s^im^p^o^s^ed^sh^o^u^ld^m^a^tch^W^o^u^l^{d au}^th^{orize FDA}^to^aⁿ^d^fo^r^ne^w^sa^fe^t^y
ⁱ^{ki/CRS-RL33925}^p^ecifⁱ^{c s}^a^f^e^ty^con^cern^s^an^{d ben}^e^f^its^en^t^e^{d by}^t^h^{e dru}^g^produ^ct^{. T}^h^{e ri}^s^k^r^e^q^u^ir^{e lim}^itatioⁿ^s^oⁿ^th^e^di^s^t^ri^bu^tⁱ^oⁿ^of^{a dru}^g^orⁱⁿ^f^o^r^m^atioⁿ^.^W^o^u^l^d^allo^w^a^sp^oⁿ^so^r^to^sub^m^{it a}^RE^M^S
^g/w^ssm^eⁿ^{t a}ⁿ^d^rⁱ^{sk m}^a^na^ge^m^e^{nt p}^r^o^g^r^a^m^biolog^{ic. T}^h^es^{e in}^clu^d^e:^as^s^e^s^s^m^en^{t at an}^y^tim^e.
^s^.or^yⁱⁿ^clu^d^e:^W^o^u^l^{d au}^th^{orize th}^e
^le^ak^Secretary^{to requ}^{ire a R}^E^MS
^as^s^e^s^s^m^en^{t at an}^y^tim^{e th}^e
^://wiki^Secretary^determⁱⁿ^es^th^at
^h^ttpⁿ^e^w^saf^e^tyⁱⁿ^f^o^r^m^atioⁿ
^requⁱ^r^es^revⁱ^ew^.
^Wou^l^{d requ}ⁱ^r^{e t}^h^at^W^o^u^l^d^allo^w^th^{e f}^o^llo^wⁱⁿ^g
^r^e^st^rⁱ^c^tⁱ^o^{ns b}^e^c^o^m^m^e^nsur^a^t^e^res^t^ri^ctⁱ^oⁿ^s^on^di^s^t^ri^bu^tⁱ^oⁿ^or
^w^{ith the}^rⁱ^{sks; ne}^c^e^ssa^r^y^{; a}ⁿ^d^u^s^{e du}^rin^g^s^t^u^d^y^if^Secretary
^no^t^und^ul^y^b^u^r^d^eⁿ^so^m^e^oⁿ^d^e^ter^mⁱⁿ^{es it n}^ecessar^y^to
^patien^t^acces^s^{to dru}^g^s^.^eⁿ^sur^e^sa^fe^ty^aⁿ^d
^W^o^u^l^{d au}^th^{orize FDA}^to^ef^f^ectiv^en^es^s^(Secretary^m^a^y
^r^e^q^u^ir^{e lim}^itatioⁿ^s^oⁿ^a^{order t}^h^{e res}^t^ri^ctⁱ^oⁿ^s
^produ^ct^’^s^di^s^t^ri^bu^tⁱ^oⁿ^.^T^h^es^e^coⁿ^tin^u^e^d^,^ter^mⁱⁿ^ated^{, o}^r
ⁱⁿ^clu^d^e:^ch^an^g^e^{d bas}^e^{d on}^s^t^u^d^y
^res^u^l^t^s^):

CRS-18
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
ⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^co^m^p^lia^nce^ch^an^g^e^{s in}^lab^e^lin^g^;^ch^an^g^e^{s in}^lab^e^lin^g^;
^th^agen^c^y-iⁿⁱ^tⁱ^a^ted^ch^an^gesⁱⁿ^d^r^u^g
^.
^Distrⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^sp^ecifⁱ^c^s^t^atem^en^tsⁱⁿ^adv^e^rtis^em^en^ts^;^d^is^clos^u^r^{e in}^adv^e^rtis^em^en^ts
^rning^s^t^o^{be inco}^rp^oratedⁱⁿ^{to al}^l^th^{at th}^{e av}^ailab^l^{e in}^f^o^r^m^atioⁿ
^om^oti^oⁿ^a^l^m^a^teri^al^s⁽ⁱⁿ^c^l^u^diⁿ^g^broadcas^t^m^a^yⁿ^o^{t allo}^w^f^o^r^f^u^ll
^{C [}^dⁱ^r^e^c^t^-t^o^-^c^o^nsum^e^r^]^a^d^ve^r^tⁱ^sⁱ^ng)^.^a^sse^ssm^eⁿ^{t o}^f^se^rⁱ^o^u^{s r}ⁱ^sks;
^{or, if}^th^{e Secretary}
^d^e^ter^mⁱⁿ^{es it n}^ecessar^y^,
^s^t^atem^en^{t in}^adv^e^rtis^em^en^ts
^r^e^ga^r^dⁱ^{ng r}ⁱ^{sk o}^r^use
ⁱⁿ^f^o^r^m^atioⁿⁱⁿ^clu^d^edⁱⁿ^th^e
^lab^e^l.
ⁱ^{ki/CRS-RL33925}ⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^{a m}^o^r^a^to^rⁱ^u^m^FD^A⁽^t^he^ne^w^Ce^nt^e^r⁾^FDA^r^e^view^o^f^res^t^ri^ctⁱ^oⁿ^s^on^DT^C
^g/w^{direct to cons}^um^{er advertis}^ing^.^revⁱ^ew^of^adv^e^rtis^em^en^ts^adv^e^rtis^em^en^ts^bef^o^{re th}^ey^a^d^ve^r^tⁱ^sⁱ^ng;
^s^.or^bef^o^{re th}^ey^{are releas}^ed;^{are releas}^ed;
^le^ak
ⁱ^s^t^ri^bu^tⁱ^oⁿ^res^{tricted to certain}^p^a^tien^t^o^r^p^h^y^s^ician^trainⁱⁿ^g^,^ex^perien^{ce, or}^cer^tain^f^{acilities o}^r^p^h^y^s^ician
^://wiki^cilit^{ies, pha}^rm^a^c^ist^s^{, o}^r^phy^siciaⁿ^s^w^ith^edu^cation^;^cer^tif^icatioⁿ^o^f^h^ealth^car^e^trainⁱⁿ^g^{or ex}^perien^ce;
^h^ttp^{ecial train}ⁱⁿ^g^{or ex}^perien^ce.^prov^iders^,^ph^arm^acis^t^s^,^an^d
^{care s}^e^ttin^g^,^{or u}^s^{e on}^lyⁱⁿ
^cer^tain^settin^g^s^;
^{a com}^p^lian^{ce s}^y^s^t^em^w^ith
^res^t^ri^ctⁱ^oⁿ^s^on^provⁱ^d^ers^,
^ph^arm^acis^t^s^,^patien^t^s^,^an^d
^o^t^h^e^r^s^w^h^o^f^a^{il to}^m^eet
^requ^irem^en^ts^;
ⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^th^e^d^o^c^u^m^en^tatioⁿ^o^f^saf^e^-^u^se^perf^orm^aⁿ^{ce of}^s^p^ecifⁱ^ed
^orm^aⁿ^{ce of}^s^p^{ecified m}^e^dical^coⁿ^d^itioⁿ^s^{, su}^ch^as^m^e^{dical procedu}^r^es^;

^[^e^.^g^.^,^r^e^q^uⁱ^rⁱ^{ng a}^p^r^e^gna^nc^y^t^e^st^lab^o^r^ato^r^y^{test r}^e^su^lts;
^g^mⁱ^g^h^t^cau^s^e^abn^o^rm^{al f}^e^tal
^e^l^opm^en^t^]^.

CRS-19
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
ⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^th^e^th^{e estab}^lish^m^en^{t o}^f^{a r}ⁱ^sk^{a n}^e^w^pos^t^-^approv^al^s^t^u^d^y^or
^orm^aⁿ^{ce of}^s^p^eci^fi^ed^ad^dⁱ^ti^on^al^clⁱⁿⁱ^c^al^m^a^na^ge^m^e^nt^p^l^aⁿ^;^ch^an^g^e^sⁱⁿ^th^{e des}ⁱ^gⁿ^of^an
^{or other s}^t^udies^.^o^ngoⁱ^{ng st}^ud^y^,^t^h^a^t^FD^A
^cou^l^{d requ}^es^{t at th}^{e tim}^{e of}
^ap^p^r^o^v^al/licen^su^r^e^o^r^an^y
^tim^{e af}^terw^ard;
^Distrⁱ^b^u^tioⁿ^coⁿ^d^itioⁿ^e^d^oⁿ^th^e^a^p^a^tⁱ^e^nt^r^e^gi^st^r^y^;^a^p^a^tⁱ^e^nt^r^e^gi^st^r^y^o^r^p^a^tⁱ^e^nt
ⁱⁿ^ten^aⁿ^{ce of}^an^{active advers}^{e event}^m^oⁿⁱ^t^o^rⁱ^ng;
^eilla^{nce sy}^st^em^.
^p^a^tⁱ^e^nt^{s t}^o^si^{gn a}^c^o^nseⁿ^t
^fo^r^m^;
^m^o^dⁱ^fⁱ^catioⁿ^o^fⁱⁿ^dⁱ^catioⁿ^;^m^o^dⁱ^fⁱ^catioⁿ^o^fⁱⁿ^dⁱ^catioⁿ^.
ⁱ^{ki/CRS-RL33925}
^g/w^th^{e m}^oⁿ^ito^rⁱⁿ^g^o^f^{sales an}^d
^s^.or^u^s^ag^e.
^le^ak
^F^o^{r a dru}^g^approv^ed
^://wiki^pu^rs^u^aⁿ^t^{to accelerated}
^h^ttp^approv^al^:
^w^o^u^l^d^r^e^q^u^ir^{e, as a co}ⁿ^d^itioⁿ
^of^approv^al^{, t}^h^at^t^h^{e s}^pon^s^o^r
^s^u^bm^{it an}^{d th}^{e Secretary}
^approv^{e prot}^ocol^s^f^o^r
^p^o^s^tm^ar^k^e^{t stu}^d^{ies, in}^clu^dⁱⁿ^g
^tim^ef^r^a^m^e^an^d^m^ilestoⁿ^es.
^Un^{til th}^{e stu}^d^y^co^m^m^itm^en^ts
^{are com}^p^{leted, Secretary}
^m^u^{st r}^e^q^u^ir^{e r}^e^strⁱ^ctioⁿ^s^oⁿ
^di^s^t^ri^bu^tⁱ^oⁿ^an^{d u}^s^e;

CRS-20
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^w^o^u^l^{d al}^s^o^requⁱ^r^{e a}
^statem^en^{t o}ⁿ^lab^e^lin^g^th^{at th}^e
^dru^g^receiv^e^{d accelerated}
^approv^al^an^{d t}^h^at^requⁱ^r^ed
^s^t^u^d^ies^{are u}ⁿ^d^erw^a^y^;^to
ⁱⁿ^clu^d^{e a list o}^f^issu^{es b}^eⁱⁿ^g
^addres^s^e^d;^an^{d l}^a^belⁱⁿ^g^t^o
^s^t^{ate th}^{at FDA}^g^a^v^e
^coⁿ^d^itioⁿ^a^{l ap}^p^r^o^v^{al u}ⁿ^d^er
^its^{accelerated approv}^al
^proces^s^;^an^{d th}^{at th}^{e dru}^g
^w^{ill n}^o^{t receiv}^e^f^u^{ll ap}^p^r^o^v^al
^uⁿ^{til co}^m^p^letioⁿ^o^f^stu^d^ies;
ⁱ^{ki/CRS-RL33925}^w^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^e^Secretary^am^en^{d 21C}^FR³¹⁴
^g/w^to^r^e^q^u^ir^{e a p}^u^b^{lic m}^eetin^g^if
^s^.or^p^o^s^tm^ar^k^e^{t stu}^d^{ies af}^ter
^le^ak^{accelerated approv}^{al are n}^o^t
^://wiki^co^m^p^leted^w^ithⁱⁿ^tw^o^y^ear^s;^an^{d w}^o^u^l^{d requ}ⁱ^r^{e, f}^o^{r a dru}^g
^h^ttp^approv^{ed bas}^e^{d on}^anⁱ^m^al
^ef^fⁱ^cacy^{data, s}^t^u^d^ies^w^h^en
^ethⁱ^{cal an}^{d f}^eas^{ible to v}^e^rif^y
^an^{d des}^c^ri^{be cl}ⁱⁿ^ci^al^ben^e^fⁱ^t^,
^s^a^f^e^ty^an^{d ef}^f^ectiv^en^es^s^.
^I^f^{a co}^m^p^leted^stu^d^y^is
ⁱⁿ^c^o^nc^l^u^si^ve⁽^o^r^no^t
^co^m^p^leted^w^ithⁱⁿ^fⁱ^v^e^y^ear^s)^,
^th^{e Secretary}^w^o^u^l^d
^wⁱ^t^h^draw^produ^ct^f^r^om
^co^m^m^e^r^c^{ial d}ⁱ^strⁱ^b^u^tioⁿ^,
^lim^itin^g^{its av}^ailab^ility^an^d
^r^e^q^u^irⁱⁿ^gⁱⁿ^f^o^r^m^ed^coⁿ^s^en^t.

CRS-21
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^at^No^{t d}ⁱ^r^ected^to^FDA^.^I^f^{a sp}^oⁿ^so^r^w^e^r^e^to^f^a^{il to}^W^o^u^l^{d au}^th^{orize civ}^{il m}^oⁿ^e^y^W^o^u^l^{d con}^s^{ider a dru}^g
^ng^{ress pro}^vⁱ^{de o}^v^ersig^ht^a^{nd ena}^c^t^aⁿ^y^co^m^p^{lete r}^e^q^u^ir^ed^stu^d^{ies o}^r^pen^a^lties^of^{$15,000 —}^mⁱ^sb^r^aⁿ^d^ed^if^{it f}^a^iled^to
^l^ation^{to en}^s^u^{re com}^p^lian^{ce by}^co^m^p^ly^w^ith^o^r^d^e^r^e^d^{$250,000 per v}ⁱ^ol^atⁱ^oⁿ⁽ⁿ^ot^co^m^p^ly^w^ith^p^o^s^tm^ar^k^e^t
^h^t^h^{e F}^D^A^an^{d dru}^g^s^pon^s^o^rs^wⁱ^t^h^t^h^e^correctiv^{e action}^,^w^o^u^l^d^to^ex^ceed^$¹^m^illioⁿ^w^ithⁱⁿ^s^t^u^d^y^{or di}^s^t^ri^bu^tⁱ^oⁿ
^o^v^isioⁿ^s^listed^ab^o^v^{e. FDA}ⁿ^eed^s^increas^e^d^au^th^o^r^{ize FDA}^to^r^e^q^u^ir^e^on^{e adj}^u^{dicated proceedin}^g⁾^r^e^q^u^ir^em^en^{ts, o}^r^lab^e^l
^{ent authority}^an^d^b^e^tter^civ^{il m}^oⁿ^e^tar^y^fⁱⁿ^e^{s o}^f^f^o^r^f^a^ilu^r^e^to^co^m^p^ly^w^ith^an^ch^an^g^e^orders^.
^{ent tools}^{directed at dru}^g^s^pon^s^o^rs^,^{$250,000 f}^o^{r t}^h^{e f}ⁱ^rs^t^30-^day^approv^{ed R}^E^MS^.
^ich^sh^o^u^ldⁱⁿ^clu^d^{e f}ⁱⁿ^e^{s, in}^j^uⁿ^c^tioⁿ^s^{, an}^d^peri^{od, dou}^blⁱⁿ^g^f^o^{r ev}^ery^W^o^u^l^{d au}^th^{orize civ}ⁱ^l
^t^h^draw^al^of^dru^g^approv^al^.^s^u^bs^equ^eⁿ^t^30-^day^peri^od^W^o^u^l^{d con}^s^{ider a dru}^g^p^eⁿ^a^{lties o}^fⁿ^o^{t m}^o^r^e^th^an
⁽ⁿ^o^t^to^ex^ceed^$²^m^illioⁿ^f^o^r^mⁱ^sb^r^aⁿ^d^ed^if^{it f}^a^iled^to^100%^(300%ⁱ^f^vⁱ^ol^atⁱ^oⁿ
^an^y^30-^day^peri^od);^ch^an^g^e^d^com^p^ly^w^ith^th^{e Secretary}^’^s^cau^s^e^{d a con}^s^u^m^{er h}^a^rm^{) of}
^prom^otⁱ^oⁿ^;^an^{d w}ⁱ^t^h^draw^al^requ^irem^en^ts^{to ch}^an^g^e^s^pon^s^o^r’^s^g^r^os^s^profⁱ^t^s^f^r^om
^of^produ^ct^approv^al^or^lab^e^lin^g^o^r^r^e^g^a^r^dⁱⁿ^g^s^a^l^e^s^of^t^h^{e dru}^g^,^{or $1}
^licen^s^u^re.^a^d^ve^r^tⁱ^sⁱ^ng.^m^illioⁿ⁽^$³^m^illioⁿ^if
ⁱ^{ki/CRS-RL33925}^If^th^{e n}^e^w^C^eⁿ^t^{er Director}^[^N^o^t^{e: A}^u^th^o^r^ity^f^o^r^c^o^nsum^e^r^ha^r^m^e^d⁾^,^w^hⁱ^c^he^ve^rⁱ^s^gr^e^a^t^e^r^.
^g/w^determⁱⁿ^{ed th}^{at a produ}^ct^ap^p^r^o^v^al/licen^su^r^e
^s^.or^m^a^y^pres^en^{t an}^uⁿ^r^eas^on^able^w^ith^draw^{al already}^ex^is^tsⁱⁿ^W^o^u^l^{d au}^th^{orize th}^{e s}^a^m^e
^le^ak^ris^k^th^{at can}ⁿ^o^{t be}^law^.^]^p^eⁿ^a^{lities f}^o^r^f^a^ilu^r^e^to^act
^://wiki^satisf^acto^r^ily^allevⁱ^ated^b^y^a^correctiv^{e action}^{or if}^a^w^ith^“^d^u^e^d^ilig^en^{ce” to}^co^m^p^{lete p}^o^s^tm^ar^k^e^{t stu}^d^ies
^h^ttp^dru^g^’^s^s^pon^s^o^{r f}^aⁱ^l^s^t^o^requⁱ^r^{ed bas}^e^{d on}
^com^p^l^y^wⁱ^t^h^an^{order or}^application^s^f^o^{r a f}^a^s^t^track
^requ^irem^en^{t, th}^{e n}^e^w^C^eⁿ^t^er^produ^{ct or accelerated}
^Dir^ecto^r^{, af}^ter^coⁿ^s^u^ltatioⁿ^approv^al^of^{a n}^e^w^dru^g^f^o^{r a}
^w^ith^th^{e Dir}^ecto^r^o^f^CB^ER^s^e^riou^s^{or lif}^e-^th^reatenⁱⁿ^g
^{or C}^B^ER^{, cou}^l^{d w}ⁱ^t^h^draw^or^illn^ess.
^s^u^s^p^en^{d t}^h^{e produ}^ct^’^s
^ap^p^r^o^v^al/licen^su^r^e^.^W^o^u^l^{d als}^o^con^s^{ider a dru}^g
^to^b^e^mⁱ^sb^r^aⁿ^d^ed^if^a
^m^a^nufa^c^t^ur^e^r^faⁱ^l^e^d^t^o
^com^p^ly^w^ith^th^{e Secretary}^’^s
^{order t}^o^m^a^k^e^s^p^eci^fⁱ^{c l}^a^bel
^ch^an^g^e^s^{to en}^s^u^{re s}^a^f^e^an^d
^ef^f^ectiv^{e u}^s^{e of}^th^{e dru}^g^.

CRS-22
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^{e Secretary}^w^o^u^l^{d h}^a^v^e^to
^p^u^b^lishⁱⁿ^th^{e Fed}^e^r^a^l
^R^e^gⁱ^s^t^{er an}^{d pos}^t^on^t^h^e
^Iⁿ^terⁿ^{et d}^e^{tails r}^e^g^a^r^dⁱⁿ^g
^reas^on^{, f}^actu^a^{l bas}ⁱ^s^,^an^d
^ref^e^ren^{ce t}^o^s^u^pportⁱⁿ^g
^em^{pirical data, f}^o^r
^d^e^ter^mⁱⁿ^atioⁿ^;^ex^p^l^an^atioⁿ
^t^h^at^des^c^ri^bes^w^h^y^con^t^rary
^{data are in}^s^u^f^fⁱ^cien^{t; an}^d
^p^o^s^itioⁿ^tak^eⁿ^b^y^each
ⁱⁿ^di^vⁱ^du^al^con^s^u^l^t^e^d.
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^at^{Not directed to FDA}^.^Doesⁿ^o^{t s}^p^ecif^y^s^p^ecial^Doesⁿ^o^{t s}^p^ecif^y^s^p^ecial^F^o^{r dru}^g^s^approv^{ed u}ⁿ^d^er
ⁱ^{ki/CRS-RL33925}ⁿ^g^r^es^s^am^en^{d th}^{e FFDC}^A^{to requ}^{ire th}^at^{carry a s}^p^{ecial s}^y^m^b^ol^suc^h^s^y^m^bol^.^sy^m^b^o^l^{, b}^u^{t allo}^w^s^FDA^to^requ^{ire s}^t^atem^en^{t in}^ads^.^{accelerated approv}^al^procedu^r^es^{, w}^o^u^l^{d requ}ⁱ^r^{e a}
^g/w^th^{e black}^trian^g^l^{e u}^s^{ed in}^th^{e UK or an}^W^o^u^l^{d au}^th^{orize FDA}^,^f^o^r^[N^ot^e:^A^s^of^Jan^u^a^ry^2006,^statem^en^{t o}ⁿ^lab^e^lin^g^th^{at th}^e
^s^.or^ui^va^l^e^nt^sy^m^b^o^l^f^o^{r new}^drug^s^,^new^tw^o^y^ear^{s af}^terⁱⁿ^itial^F^D^A^requⁱ^r^es^dat^e^of^dru^g^receiv^e^{d accelerated}
^le^ak^m^b^ina^t^io^ns^of^activ^{e s}^u^bs^tan^ces^{, an}^d^new^ap^p^r^o^v^al/licen^su^r^e^an^d^f^o^r^all^approv^al^bu^tⁿ^o^t^{a s}^y^m^bol^on^approv^al^an^{d t}^h^at^requⁱ^r^ed
^st^e^m^{s o}^f^de^liv^e^r^y^o^f^e^xⁱ^s^tⁱ^{ng d}^r^ugs.^T^h^e^d^r^u^g^s^w^ith^o^u^tstan^dⁱⁿ^g^lab^e^l.]^s^t^u^d^ies^{are u}ⁿ^d^erw^a^y^,^an^{d to}
^://wiki^sho^u^ld^res^tri^c^{t d}ⁱ^rect-to-con^s^u^m^e^r^r^e^q^u^ir^ed^stu^d^{ies, to}^r^e^q^u^ir^eⁱⁿ^clu^d^{e a list o}^f^issu^{es b}^eⁱⁿ^g
^h^ttp^v^ert^ising^du^riⁿ^g^t^h^{e peri}^{od of}^tⁱ^m^{e t}^h^e^preapprov^al^s^u^bmⁱ^s^sⁱ^on^of^May^requⁱ^r^{e s}^u^bmⁱ^s^sⁱ^on^of^addres^s^e^{d. Wou}^l^{d al}^s^o
^{ecial s}^y^m^{bol is}ⁱⁿ^ef^f^ect.^p^r^o^m^o^tioⁿ^a^{l m}^a^terⁱ^{al, an}^d^to^ad^v^e^r^tisem^en^{ts to}^FDA^f^o^r^r^e^q^u^ir^{e lab}^e^lin^g^to^{state th}^at
^requ^{ire a s}^t^atem^en^{t th}^{at th}^e^preclearan^{ce; s}^p^ecifⁱ^c^FDA^g^a^v^e^coⁿ^d^itioⁿ^a^l
^produ^ctⁱ^sⁿ^e^w^.^dⁱ^sc^lo^sur^e^{s in}^approv^al^uⁿ^d^{er i}^t^s
^ad^v^e^r^tisem^en^{ts, w}^h^ich^m^a^y^{accelerated approv}^{al proces}^s^;
ⁱⁿ^clu^d^{e approv}^{al date,}^an^d^th^{at th}^{e d}^r^u^g^w^{ill n}^o^t
^s^t^atem^en^{t th}^{at “}^e^xⁱ^s^tin^g^receiv^e^f^u^{ll approv}^{al u}ⁿ^til
ⁱⁿ^fo^r^m^a^tⁱ^o^{n m}^a^y^no^t^ha^ve^co^m^p^letioⁿ^o^f^stu^d^ies.

^id^en^tif^ied^o^r^f^u^lly^assessed
^a^{ll se}^rⁱ^o^u^{s r}ⁱ^{sks o}^f^{using the}
^dru^g^,^{” s}^e^riou^s^adv^e^rs^{e ev}^en^ts
^listedⁱⁿ^d^r^u^g^’^{s lab}^e^lin^g^,^o^r
^“^p^r^o^to^co^{l to}^en^su^r^e^saf^e^u^s^e
^des^c^ri^{bed i}ⁿ^t^h^{e l}^a^belⁱⁿ^g^of
^th^{e dru}^g^....”

CRS-23
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^May^requⁱ^r^{e t}^e^m^porary
^m^o^rat^o^ri^u^m^on^di^rect^-^t^o-
^con^s^u^m^{er adv}^e^rtis^em^en^ts^f^o^r
^u^p^to^tw^o^y^ear^{s af}^terⁱⁿ^itial
^approv^{al if}^Secretary
^det^e^rmⁱⁿ^es^ot^h^e^{r requ}ⁱ^r^ed
^dⁱ^sclo^su^r^e^{is in}^ad^eq^u^a^{te to}
^prot^ect^pu^blⁱ^c^h^eal^t^h^an^d
^s^a^f^e^ty^{, an}^{d th}^{at s}^u^ch
^p^r^o^h^ib^itioⁿ^{is n}^ecessary
^w^h^{ile ad}^d^itioⁿ^a^{l in}^f^o^r^m^atioⁿ
^is^{collected, con}^s^iderin^g
^ex^{pected s}^c^{ope of}^u^s^e,
^alterⁿ^ativ^{es, an}^d^th^{e ex}^ten^t^to
ⁱ^{ki/CRS-RL33925}^w^hⁱ^c^{h st}^udⁱ^e^{s use}^d^t^o^approv^{e t}^h^{e dru}^g^m^a^yⁿ^o^t
^g/w^ha^ve^id^eⁿ^tifie^d^se^rⁱ^o^u^{s r}ⁱ^sks.
^s^.or
^le^ak^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^at^FDA^Co^nd^uc^tⁱ^{ng p}ⁱ^l^o^t^d^e^ve^l^o^p^e^d^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^a^l^ua^t^e^a^{ll new}^da^t^a^oⁿ^new^m^o^lecula^r^b^y^{OSE an}^d^{OND to}^revⁱ^ew
^://wiki^ti^ti^esⁿ^o^l^a^{ter th}^an^fi^{ve years}^after^sy^stem^atically^th^{e saf}^e^ty
^h^ttp^p^r^oval^{. Sp}^oⁿ^so^r^s^w^{ill su}^b^m^{it a r}^e^p^o^r^{t o}^f^profⁱ^l^e^s^ofⁿ^e^w^m^o^l^ecu^l^a^r
^m^u^{lated data relev}^aⁿ^t^{to dru}^g^s^a^f^e^ty^an^d^en^{tities o}ⁿ^{a r}^e^g^u^l^ar^ly
ⁱ^cacy^{, in}^clu^dⁱⁿ^g^an^y^ad^d^itioⁿ^a^{l d}^a^ta^s^c^h^e^du^l^e^{d bas}ⁱ^s^t^o^det^e^rmⁱⁿ^e
^blis^h^e^{d in}^{a peer rev}ⁱ^ew^{ed j}^o^u^rⁿ^a^{l, an}^{d w}^ill^w^h^eth^e^{r th}^es^{e rev}ⁱ^ew^s^s^h^ou^ld
^th^{e s}^t^atu^s^of^an^y^applicable^b^eⁱⁿ^itiated^f^o^r^{all NMEs.}
ⁿ^d^itioⁿ^s^im^p^o^s^ed^oⁿ^th^{e d}ⁱ^strⁱ^b^u^tioⁿ^o^f^th^e^W^{ill in}^co^r^p^o^r^{ate A}^E^{RS d}^a^ta,
^u^g^called^f^o^r^{at o}^r^af^ter^th^{e tim}^{e o}^f^d^a^t^a^mⁱⁿⁱ^{ng a}ⁿ^a^l^y^sⁱ^s^,
^al^.^ep^id^em^io^lo^gⁱ^{c d}^a^ta,
^p^o^s^tm^ar^k^e^tin^g^clin^{ical tr}^ial
ⁱⁿ^f^o^rm^ation^,^an^{d a rev}ⁱ^ew^of
^t^h^{e Peri}^odi^{c S}^a^f^e^t^y^U^pdat^e
^R^e^port^s^(U^.S^{. Peri}^odi^c
^Rep^o^r^ts)^to^id^en^tif^y^p^o^t^en^tial
^s^a^f^e^ty^con^cern^s^earlyⁱⁿ^th^e
^produ^{ct lif}^{e cy}^cle.

CRS-24
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^m^m^unica^tioⁿ
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^at^E^s^t^a^b^lⁱ^s^hi^{ng a}^ne^w^a^d^vi^so^r^y^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.^N^o^provⁱ^sⁱ^oⁿ^.

^ngr^e^{ss e}ⁿ^a^c^t^l^e^gi^sl^a^tⁱ^o^{n e}^s^t^a^b^lⁱ^s^hi^{ng a}^ne^w^com^m^{ittee reg}^a^rdin^g^FDA^’^s
^advis^o^{ry com}^mⁱ^{ttee on}^co^m^m^uⁿⁱ^catioⁿ^p^o^{licies an}^d
^m^{unication w}ⁱ^th^pa^tⁱ^ent^s^aⁿ^d^practices^{; m}^e^m^b^ers^w^ill
^um^ers^{. T}^h^{e com}^m^{ittee w}^o^u^l^{d be}ⁱⁿ^clu^d^{e patien}^t^s^an^d
^pos^{ed of}^m^e^m^b^ers^w^h^{o repres}^en^t^con^s^u^m^ers^an^{d ex}^pertsⁱⁿ
^s^u^m^{er an}^{d patien}^t^pers^pectiv^es^an^d^ris^k^an^{d cris}^is
^aⁿⁱ^zation^s^{. T}^h^{e adv}ⁱ^s^o^ry^com^m^{ittee w}^o^u^l^d^com^m^uⁿⁱ^cation^an^{d s}^o^cial
ⁱ^s^e^C^B^ER^an^{d oth}^e^{r FDA}^cen^ters^on^an^d^co^gⁿ^itiv^{e scien}^ces.
^m^uⁿⁱ^cation^is^s^u^es^{related to ef}^fⁱ^cacy^,
^f^e^ty^{, an}^{d u}^s^{e du}^rin^g^th^{e lif}^ecy^{cle of}^dru^g^s
^{d ot}^h^e^{r m}^e^di^cal^produ^ct^s^,^an^{d i}^t^w^o^u^l^d
ⁱ^{ki/CRS-RL33925}^pport^t^h^{e cen}^t^e^rsⁱⁿ^t^h^ei^{r m}ⁱ^s^sⁱ^on^t^o^“^h^el^p^{blic g}^e^{t th}^{e accu}^{rate, s}^c^ien^ce-^bas^e^d
^g/w^o^rm^ation^th^eyⁿ^{eed to u}^s^{e m}^e^dicin^e^s^an^d
^s^.or^t^oⁱ^m^prov^{e t}^h^ei^{r h}^eal^t^h^.”
^le^ak
^://wiki
^h^ttp

CRS-25
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^T^h^e^com^m^{ittee recom}^m^eⁿ^d^s^th^{at th}^e^E^s^t^a^b^lⁱ^s^he^d^a^w^o^r^kⁱ^{ng gr}^o^u^p^Wou^l^{d requ}ⁱ^r^{e t}^h^at^F^D^A^W^o^u^l^{d au}^th^{orize FDA}^to^N^o^provⁱ^sⁱ^oⁿ^.

^O^f^fⁱ^{ce o}^f^Drug^Sa^f^e^t^y^P^o^licy^aⁿ^d^t^o^dev^e^l^{op a C}^B^ER^ri^s^k^m^a^k^e^saf^e^ty^issu^{es p}^u^b^{lic v}ⁱ^a^requⁱ^r^{e a MedG}^uⁱ^{de or}
^m^m^uⁿⁱ^cati^on^s^h^ou^l^d^d^e^vel^o^p^{a coh}^e^sⁱ^ve^c^o^m^m^uni^c^a^tⁱ^o^{n st}^r^a^t^e^gi^c^th^{e Federal R}^e^gⁱ^s^t^{er an}^d^patien^t^pack^ag^{e in}^s^e^{rt, an}^{d a}
^k^com^m^{unication plan}^th^{at in}^clu^d^es^{, at a}^p^l^an^{. Do}ⁱⁿ^g^so^w^{ill ex}^p^l^o^r^e^Iⁿ^terⁿ^{et, b}^u^{t d}^o^e^{s n}^o^{t r}^e^q^u^ir^e^com^m^uⁿⁱ^cation^plan^to
ⁿⁱ^m^u^m^,^{a rev}ⁱ^ew^of^{all C}^eⁿ^t^{er ris}^k^com^m^uⁿⁱ^cation^tools^,^an^d^dev^e^l^opm^en^t^of^{a pl}^an^.^provⁱ^d^ers^.
^m^m^uⁿⁱ^catioⁿ^activ^{ities, ev}^alu^a^tioⁿ^an^d^ev^alu^a^{te an}^{d im}^prov^{e th}^e
ⁱ^sⁱ^on^of^com^m^uⁿⁱ^cation^tools^f^o^{r clarity}^CB^{ER w}^e^b^s^ite.^W^o^u^l^d^r^e^q^u^ir^{e th}^{at, n}^o^{t less}^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^e
^d^coⁿ^s^isten^c^y^,^an^d^p^r^io^r^ity^-^s^ettin^g^to^en^su^r^e^th^an^ev^ery^{90 day}^s^{, th}^e^Secretary^,^w^ithⁱⁿ^on^{e y}^ear,
ⁱ^cien^{t u}^s^{e of}^res^o^u^r^ces^.^Estab^lish^e^d^th^e^Secretary^pu^blis^hⁱⁿ^th^e^su^b^m^{it to}^coⁿ^g^r^{ess an}
^Bⁱ^oⁱⁿ^f^o^r^m^a^{tics B}^o^ar^dⁱⁿ^th^e^Fed^e^r^a^{l Register}^:^a^sse^ssm^eⁿ^{t o}^f^the
^Of^fⁱ^{ce of}^th^{e C}^o^m^mⁱ^s^sⁱ^on^erⁱⁿ^f^o^r^m^atioⁿ^ab^o^u^{t r}^e^q^u^ir^edⁱⁿ^f^o^r^m^atioⁿ^techⁿ^o^lo^g^y⁽^I^T⁾
^to^im^p^r^o^v^{e th}^{e p}^u^b^lic’^s^stu^d^{ies to}ⁱⁿ^clu^d^{e ty}^p^e^,ⁱⁿ^f^r^astr^u^c^tu^r^e⁽^d^ata
^ab^ility^to^co^m^m^uⁿⁱ^{cate w}^ithⁿ^a^t^u^{re, ou}^t^c^om^es^{, dat}^e^co^llectioⁿ^an^d^d^a^{ta m}ⁱⁿⁱⁿ^g
^FD^A^,ⁱⁿ^c^l^udⁱ^{ng a}^d^ve^r^s^e^requ^{ired by}^FDA^{or ag}^reed^s^y^s^t^em^s^,^an^{d ex}^tern^al
ⁱ^{ki/CRS-RL33925}^ev^en^{t reports}^an^{d con}^s^u^m^er^co^m^p^lain^ts.^t^o^by^s^pon^s^o^{r, dat}^e^f^o^r^com^p^letion^,^an^{d reas}^on^th^at^dat^a^bas^e^an^{d pers}^onⁿ^e^l^as^s^e^t^s^an^{d t}^r^aiⁿⁱⁿ^g^prog^ram^s⁾
^g/w^an^y^stu^d^y^w^a^{s n}^o^{t co}^m^p^leted^th^{at FDA}^w^o^u^l^{d n}^{eed to:}
^s^.or^by^deadlⁱⁿ^e;^prog^res^s^report^s^coⁿ^d^u^c^{t th}^{e activ}^{ities th}^at
^le^ak^an^d^r^e^su^{lts o}^f^co^m^p^leted^th^{is b}^{ill w}^o^u^l^d^r^e^q^u^ir^e;
^://wiki^s^t^u^d^ies^;^an^{d ex}^plan^ation^s^of^th^{e n}^e^w^C^eⁿ^t^{er Director’}^s^ach^iev^eⁱⁿ^ter^o^p^e^r^a^b^ility^am^on^g^FDA^C^eⁿ^t^ers^an^d
^h^ttp^d^e^ter^mⁱⁿ^atioⁿ^s^{, if}^an^y^.^produ^ct^s^pon^s^o^rs^;^an^{d u}^s^e
^electronⁱ^{c h}^ealth^records^.
^A^l^s^o^requⁱ^r^{ed w}^o^u^l^{d be an}
^a^sse^ssm^eⁿ^{t o}^f^w^h^e^t^he^r^tho^s^e
^as^s^e^ts^w^e^{re s}^u^f^fⁱ^cien^{t, a plan}
^fo^r^e^nha^ncⁱ^{ng FD}^A^’^{s I}^T
^a^sse^ts,^aⁿ^d^aⁿ^a^sse^ssm^eⁿ^{t o}^f
^w^h^{at ad}^d^itioⁿ^a^{l r}^e^so^u^r^ces
^FD^A^w^o^ul^d^ne^e^d^t^o^m^a^ke
^th^os^{e IT}^en^h^aⁿ^cem^en^ts^.

CRS-26
^Inst^it^ut^{e o}^f^M^e^dicine^FD^A^Jan^u^a^{ry 2007}^S^.^{468, G}^r^as^s^l^ey-D^od^d^-^Mⁱ^k^u^l^s^kⁱ^-Biⁿ^gam^an^&^S^.^{484, E}ⁿ^zi^-Kenⁿ^e^d^y^H.R^.^{1165, M}^a^rk^ey
^e^p^t^em^b^{er 2006 rep}^{ort recom}^m^eⁿ^d^a^tion^s^res^pons^{e to I}^O^M^report^H.R^.^{788, T}ⁱ^ern^ey-R^am^s^t^ad
^Wou^l^{d requ}ⁱ^r^{e t}^h^{e H}^H^S^W^o^u^l^d^r^e^q^u^ir^{e th}^{at th}^e
^Secretary^,ⁱⁿ^con^s^u^ltation^Se^c^r^e^t^a^r^y^,^t^h^r^o^{ugh FD}^A^aⁿ^d
^w^ith^th^{e FDA}^Co^m^mⁱ^ssioⁿ^er^th^{e Natio}ⁿ^a^{l I}ⁿ^stitu^{tes o}^f
^an^{d th}^{e Directors}^of^th^{e n}^e^w^Health^{, estab}^lish^{a p}^u^b^licly
^C^eⁿ^t^{er an}^{d C}^D^R^H^{, to s}^u^bm^it^av^{ailable, s}^earch^able
^{a report}^t^o^C^oⁿ^g^r^es^s^abou^t^reposⁱ^t^o^ry^of^s^t^ru^ct^u^r^ed,
^cu^rren^t^pos^tm^ark^e^t^electronⁱ^{c produ}^ct
^su^r^v^eillan^{ce o}^f^FDA^-ⁱⁿ^f^o^r^m^atioⁿ^;^an^d^r^e^p^o^r^t
^approv^{ed m}^e^di^cal^devⁱ^ces^p^r^o^g^r^e^{ss a}^nnua^l^l^y^t^o
^th^{at id}^en^tif^{ies g}^a^p^s^,^Co^ngr^e^ss.
^recom^m^eⁿ^d^s^w^a^y^s^to
^im^p^r^o^v^{e th}^em^{, an}^d^id^en^tif^ies
^ch^an^g^e^sⁱⁿ^au^th^orityⁿ^eeded
^to^m^a^k^e^th^o^s^{e im}^p^r^o^v^em^en^ts,
ⁱ^{ki/CRS-RL33925}^r^eco^gⁿⁱ^zin^g^th^{e leg}^itim^ate^dif^f^e^ren^ces^betw^een^devⁱ^ces
^g/w^an^{d ot}^h^e^{r m}^e^di^cal^produ^ct^s^.
^s^.or
^le^ak^s^o^ur^ces
^://wiki^T^{o s}^u^pportⁱ^m^prov^em^en^t^sⁱⁿ^drug^No^{tes th}^{at P}^DUFA^{IV f}^uⁿ^d^s,^Wou^l^{d au}^t^h^ori^z^e^W^o^u^l^{d au}^th^{orize th}^{e u}^s^{e of}^N^o^provⁱ^sⁱ^oⁿ^.

^h^ttp^{fety and efficacy activities}^{over a}^w^h^ich^requ^{ire con}^g^r^es^sⁱ^on^al^a^p^p^r^o^p^rⁱ^a^tⁱ^o^{ns (}^b^e^gⁱⁿⁿⁱ^ng^P^D^U^F^{A fe}^e^s^fo^r^sa^fe^t^y
^duct^’^{s lif}^ecy^cle^{, th}^{e co}^m^m^ittee^a^c^tⁱ^o^n,^w^o^ul^d^no^t^b^e^w^ith^{$50 m}^illionⁱⁿ^FY2008,^activ^{ities sp}^ecifⁱ^edⁱⁿ^th^is
^m^m^eⁿ^d^{s th}^{at th}^{e A}^d^mⁱⁿⁱ^str^a^tioⁿ^sh^o^u^ld^su^f^fⁱ^cien^{t to}^f^u^lly^im^p^l^em^en^t^g^oⁱⁿ^g^{to $150 m}^illionⁱⁿ^b^{ill; w}^o^u^l^d^am^en^d^th^e
^es^t^an^{d C}^oⁿ^g^r^es^s^s^h^ou^l^d^approv^e^th^{e IOM recom}^m^eⁿ^d^ation^s^.^F^Y^{2012) t}^o^carry^ou^t^t^hⁱ^s^PD^U^F^A^provⁱ^sⁱ^oⁿ^s^{[21 U}^S^C
^b^s^tan^tially^increas^e^{d res}^ources^{in both}^b^ill’^{s p}^r^o^v^isioⁿ^s^.^{379(c)(2)] t}^oⁱⁿ^cl^u^d^e
^{nd perso}^nnel^fo^r^t^h^e^F^D^A.^direction^s^f^o^{r th}^{e Secretary}^’^s
^calcu^latioⁿ^o^f^w^o^r^k^lo^ad
^a^d^j^u^st^m^e^nt^{s fo}^r^a^nnua^l
^adj^u^s^t^m^eⁿ^t^s^{to f}^ees^.