172 
the period during which an application may not be 
approved 
under 
section 
505(c)(3) 
or 
section 
505(j)(5)(B) shall be extended by a period of 6 
months after the date the patent expires (including 
any patent extensions); or 
‘‘(B) if the drug is the subject of a listed patent 
for which a certification has been submitted under 
subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of sec-
tion 505, and in the patent infringement litigation 
resulting from the certification the court determines 
that the patent is valid and would be infringed, the 
period during which an application may not be ap-
proved 
under 
section 
505(c)(3) 
or 
section 
505(j)(5)(B) shall be extended by a period of 6 
months after the date the patent expires (including 
any patent extensions). 
‘‘(c) RELATION TO PEDIATRIC AND QUALIFIED IN-
FECTIOUS DISEASE PRODUCT EXCLUSIVITY.—Any exten-
sion under subsection (b) of a period shall be in addition 
to any extension of the periods under sections 505A and 
505E of this Act and section 351(m) of the Public Health 
Service Act, as applicable, with respect to the drug. 
‘‘(d) LIMITATIONS.—The extension described in sub-
section (b) shall not apply if the drug designated under
173 
subsection (a)(1) has previously received an extension by 
operation of subsection (b). 
‘‘(e) DEFINITION.—In this section, the term ‘rare 
disease or condition’ has the meaning given to such term 
in section 526(a)(2).’’. 
(b) APPLICATION.—Section 505G of the Federal 
Food, Drug, and Cosmetic Act, as added by subsection 
(a), applies only with respect to a drug for which an appli-
cation or supplemental application described in subsection 
(a)(1)(B)(i) of such section 505G is first approved under 
section 505(c) of such Act (21 U.S.C. 355(c)) or section 
351(a) of the Public Health Service Act (42 U.S.C. 
262(a)) on or after the date of the enactment of this Act. 
(c) CONFORMING AMENDMENTS.— 
(1) RELATION TO PEDIATRIC EXCLUSIVITY FOR 
DRUGS.—Section 505A of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 355a) is amended— 
(A) in subsection (b), by adding at the end 
the following: 
‘‘(3) RELATION TO EXCLUSIVITY FOR A DRUG 
APPROVED FOR A NEW INDICATION FOR A RARE DIS-
EASE
OR
CONDITION.—Notwithstanding the ref-
erences in paragraph (1) to the lengths of the exclu-
sivity periods after application of pediatric exclu-
sivity, the 6-month extensions described in para-
174 
graph (1) shall be in addition to any extensions 
under section 505G.’’; and 
(B) in subsection (c), by adding at the end 
the following: 
‘‘(3) RELATION TO EXCLUSIVITY FOR A DRUG 
APPROVED FOR A NEW INDICATION FOR A RARE DIS-
EASE
OR
CONDITION.—Notwithstanding the ref-
erences in paragraph (1) to the lengths of the exclu-
sivity periods after application of pediatric exclu-
sivity, the 6-month extensions described in para-
graph (1) shall be in addition to any extensions 
under section 505G.’’. 
(2) RELATION
TO
EXCLUSIVITY
FOR
NEW 
QUALIFIED
INFECTIOUS
DISEASE
PRODUCTS
THAT 
ARE DRUGS.—Subsection (b) of section 505E of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355f) is amended— 
(A) by amending the subsection heading to 
read as follows: ‘‘RELATION TO PEDIATRIC EX-
CLUSIVITY AND EXCLUSIVITY FOR A DRUG AP-
PROVED FOR A NEW INDICATION FOR A RARE 
DISEASE OR CONDITION.—’’; and 
(B) by striking ‘‘any extension of the pe-
riod under section 505A’’ and inserting ‘‘any
175 
extension of the periods under sections 505A 
and 505G, as applicable,’’. 
(3) RELATION TO PEDIATRIC EXCLUSIVITY FOR 
BIOLOGICAL
PRODUCTS.—Section 351(m) of the 
Public Health Service Act (42 U.S.C. 262(m)) is 
amended by adding at the end the following: 
‘‘(5) RELATION TO EXCLUSIVITY FOR A BIO-
LOGICAL PRODUCT APPROVED FOR A NEW INDICA-
TION FOR A RARE DISEASE OR CONDITION.—Not-
withstanding the references in paragraphs (2)(A), 
(2)(B), (3)(A), and (3)(B) to the lengths of the ex-
clusivity periods after application of pediatric exclu-
sivity, the 6-month extensions described in such 
paragraphs shall be in addition to any extensions 
under section 505G.’’. 
SEC. 2152. REAUTHORIZATION OF RARE PEDIATRIC DIS-
EASE PRIORITY REVIEW VOUCHER INCEN-
TIVE PROGRAM. 
(a) IN GENERAL.—Section 529 of the Federal Food, 
Drug, and Cosmetic Act (21 U.S.C. 360ff) is amended— 
(1) in subsection (a)— 
(A) in paragraph (3), by amending sub-
paragraph (A) to read as follows: 
‘‘(A) The disease is a serious or life-threat-
ening disease in which the serious or life-threat-
176 
ening manifestations primarily affect individ-
uals aged from birth to 18 years, including age 
groups often called neonates, infants, children, 
and adolescents.’’; and 
(B) in paragraph (4)— 
(i) in subparagraph (E), by striking 
‘‘and’’ at the end; 
(ii) in subparagraph (F), by striking 
the period at the end and inserting ‘‘; 
and’’; and 
(iii) by adding at the end the fol-
lowing: 
‘‘(G) is for a drug or biological product for 
which a priority review voucher has not been 
issued under section 524 (relating to tropical 
disease products).’’; and 
(2) in subsection (b), by striking paragraph (5) 
and inserting the following: 
‘‘(5) TERMINATION OF AUTHORITY.— 
‘‘(A) IN
GENERAL.—The Secretary may 
not award any priority review vouchers under 
paragraph (1) after December 31, 2018. 
‘‘(B) EXCEPTION.—Notwithstanding sub-
paragraph (A), the sponsor of a drug that is 
designated under subsection (d) as a drug for
177 
a rare pediatric disease and that is the subject 
of a rare pediatric disease product application 
that is submitted during the period beginning 
on the date of enactment of the 21st Century 
Cures Act and ending the date specified in sub-
paragraph (A) shall remain eligible to receive a 
priority review voucher under paragraph (1) ir-
respective of whether the rare pediatric disease 
product application with respect to such drug is 
approved after the end of such period.’’. 
(b) GAO STUDY AND REPORT.— 
(1) STUDY.—The Comptroller General of the 
United States shall conduct a study on the effective-
ness of awarding priority review vouchers under sec-
tion 529 of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 360ff) in providing incentives for the 
development of drugs that treat or prevent rare pe-
diatric diseases (as defined in subsection (a)(3) of 
such section) that would not otherwise have been de-
veloped. In conducting such study, the Comptroller 
General shall examine the following: 
(A) The indications for which each drug 
for which a priority review voucher was award-
ed under such section 529 was approved under 
section 505 of such Act (21 U.S.C. 355) or sec-
178 
tion 351 of the Public Health Service Act (42 
U.S.C. 262). 
(B) Whether the priority review voucher 
impacted a sponsor’s decision to invest in devel-
oping a drug to treat or prevent a rare pedi-
atric disease. 
(C) An analysis of the drugs that utilized 
such priority review vouchers, which shall in-
clude— 
(i) the indications for which such 
drugs were approved under section 505 of 
the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 355) or section 351 of the Pub-
lic Health Service Act (42 U.S.C. 262); 
(ii) whether unmet medical needs were 
addressed through the approval of such 
drugs, including, for each such drug— 
(I) if an alternative therapy was 
previously available to treat the indi-
cation; and 
(II) the benefit or advantage the 
drug provided over another available 
therapy; 
(iii) the number of patients potentially 
treated by such drugs;
179 
(iv) the value of the priority review 
voucher if transferred; and 
(v) the length of time between the 
date on which a priority review voucher 
was awarded and the date on which it was 
used. 
(D) With respect to the priority review 
voucher program under section 529 of the Fed-
eral Food, Drug, and Cosmetic Act (21 U.S.C. 
360ff)— 
(i) the resources used by, and burden 
placed on, the Food and Drug Administra-
tion in implementing such program, includ-
ing the effect of such program on the Food 
and Drug Administration’s review of drugs 
for which a priority review voucher was not 
awarded or used; 
(ii) the impact of the program on the 
public health as a result of the expedited 
review of applications for drugs that treat 
or prevent non-serious indications that are 
generally used by the broader public; and 
(iii) alternative approaches to improv-
ing such program so that the program is 
appropriately targeted toward providing in-
180 
centives for the development of clinically 
important drugs that— 
(I) prevent or treat rare pediatric 
diseases; and 
(II) would likely not otherwise 
have been developed to prevent or 
treat such diseases. 
(2) REPORT.—Not later than December 31, 
2017, the Comptroller General of the United States 
shall submit to the Committee on Energy and Com-
merce of the House of Representatives and the Com-
mittee on Health, Education, Labor, and Pensions 
of the Senate a report containing the results of the 
study of conducted under paragraph (1). 
Subtitle 
J—Domestic 
Manufac-
turing and Export Efficiencies 
SEC. 2161. GRANTS FOR STUDYING THE PROCESS OF CON-
TINUOUS DRUG MANUFACTURING. 
(a) IN GENERAL.—The Commissioner of Food and 
Drugs may award grants to institutions of higher edu-
cation and nonprofit organizations for the purpose of 
studying and recommending improvements to the process 
of continuous manufacturing of drugs and biological prod-
ucts and similar innovative monitoring and control tech-
niques.
181 
(b) DEFINITIONS.—In this section: 
(1) The term ‘‘drug’’ has the meaning given to 
such term in section 201 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321). 
(2) The term ‘‘biological product’’ has the 
meaning given to such term in section 351(i) of the 
Public Health Service Act (42 U.S.C. 262(i)). 
(3) The term ‘‘institution of higher education’’ 
has the meaning given to such term in section 101 
of the Higher Education Act of 1965 (20 U.S.C. 
1001). 
(c) AUTHORIZATION OF APPROPRIATIONS.—There is 
authorized to be appropriated to carry out this section 
$5,000,000 for each of fiscal years 2016 through 2020. 
SEC. 2162. RE-EXPORTATION AMONG MEMBERS OF THE EU-
ROPEAN ECONOMIC AREA. 
Section 1003 of the Controlled Substances Import 
and Export Act (21 U.S.C. 953) is amended— 
(1) in subsection (f)— 
(A) in paragraph (5)— 
(i) by striking ‘‘(5)’’ and inserting 
‘‘(5)(A)’’; 
(ii) by inserting ‘‘, except that the 
controlled substance may be exported from 
the second country to another country that
182 
is a member of the European Economic 
Area’’ before the period at the end; and 
(iii) by adding at the end the fol-
lowing: 
‘‘(B) Subsequent to any re-exportation de-
scribed in subparagraph (A), a controlled substance 
may continue to be exported from any country that 
is a member of the European Economic Area to any 
other such country, provided that— 
‘‘(i) the conditions applicable with respect 
to the first country under paragraphs (1), (2), 
(3), (4), (6), and (7) are met by each subse-
quent country from which the controlled sub-
stance is exported pursuant to this paragraph; 
and 
‘‘(ii) the conditions applicable with respect 
to the second country under such paragraphs 
are met by each subsequent country to which 
the controlled substance is exported pursuant to 
this paragraph.’’; and 
(B) in paragraph (6)— 
(i) by striking ‘‘(6)’’ and inserting 
‘‘(6)(A)’’; and 
(ii) by adding at the end the fol-
lowing:
183 
‘‘(B) In the case of re-exportation among mem-
bers of the European Economic Area, within 30 
days after each re-exportation, the person who ex-
ported the controlled substance from the United 
States delivers to the Attorney General— 
‘‘(i) documentation certifying that such re- 
exportation has occurred; and 
‘‘(ii) information concerning the consignee, 
country, and product.’’; and 
(2) by adding at the end the following: 
‘‘(g) LIMITATION.—Subject to paragraphs (5) and 
(6) of subsection (f) in the case of any controlled sub-
stance in schedule I or II or any narcotic drug in schedule 
III or IV, the Attorney General shall not promulgate nor 
enforce any regulation, subregulatory guidance, or en-
forcement policy which impedes re-exportation of any con-
trolled substance among European Economic Area coun-
tries, including by promulgating or enforcing any require-
ment that— 
‘‘(1) re-exportation from the first country to the 
second country or re-exportation from the second 
country to another country occur within a specified 
period of time; or 
‘‘(2) information concerning the consignee, 
country, and product be provided prior to expor-
184 
tation of the controlled substance from the United 
States or prior to each re-exportation among mem-
bers of the European Economic Area.’’. 
Subtitle K—Enhancing 
Combination Products Review 
SEC. 2181. ENHANCING COMBINATION PRODUCTS REVIEW. 
Section 503(g)(4)(C) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 353(g)(4)(C)) is amended by 
adding at the end the following new clause: 
‘‘(iii) Not later than 18 months after the date of the 
enactment of the 21st Century Cures Act, the Secretary 
shall issue final guidance that describes the responsibilities 
of each agency center regarding its review of combination 
products. The Secretary shall, after soliciting public com-
ment, review and update the guidance periodically.’’. 
Subtitle L—Priority Review for 
Breakthrough Devices 
SEC. 2201. PRIORITY REVIEW FOR BREAKTHROUGH DE-
VICES. 
(a) IN GENERAL.—Chapter V of the Federal Food, 
Drug, and Cosmetic Act is amended— 
(1) in section 515(d)— 
(A) by striking paragraph (5); and 
(B) by redesignating paragraph (6) as 
paragraph (5); and
185 
(2) by inserting after section 515A (21 U.S.C. 
360e–1) the following: 
‘‘SEC. 515B. PRIORITY REVIEW FOR BREAKTHROUGH DE-
VICES. 
‘‘(a) IN GENERAL.—In order to provide for more ef-
fective treatment or diagnosis of life-threatening or irre-
versibly debilitating human diseases or conditions, the 
Secretary shall establish a program to provide priority re-
view for devices— 
‘‘(1) representing breakthrough technologies; 
‘‘(2) for which no approved alternatives exist; 
‘‘(3) offering significant advantages over exist-
ing approved or cleared alternatives, including the 
potential to, compared to existing approved or 
cleared alternatives, reduce or eliminate the need for 
hospitalization, improve patient quality of life, facili-
tate patients’ ability to manage their own care (such 
as through self-directed personal assistance), or es-
tablish long-term clinical efficiencies; or 
‘‘(4) the availability of which is in the best in-
terest of patients. 
‘‘(b) REQUEST FOR DESIGNATION.—A sponsor of a 
device may request that the Secretary designate the device 
for priority review under this section. Any such request 
for designation may be made at any time prior to the sub-
186 
mission of an application under section 515(c), a petition 
for classification under section 513(f)(2), or a notification 
under section 510(k). 
‘‘(c) DESIGNATION PROCESS.— 
‘‘(1) IN GENERAL.—Not later than 60 calendar 
days after the receipt of a request under subsection 
(b), the Secretary shall determine whether the device 
that is the subject of the request meets the criteria 
described in subsection (a). If the Secretary deter-
mines that the device meets the criteria, the Sec-
retary shall designate the device for priority review. 
‘‘(2) REVIEW.—Review of a request under sub-
section (b) shall be undertaken by a team that is 
composed of experienced staff and managers of the 
Food and Drug Administration and is chaired by a 
senior manager. 
‘‘(3) DESIGNATION DETERMINATION.—A deter-
mination approving or denying a request under sub-
section (b) shall be considered a significant decision 
under section 517A and the Secretary shall provide 
a written, substantive summary of the basis for the 
determination in accordance with section 517A(a). 
‘‘(4) RECONSIDERATION.— 
‘‘(A) REQUEST FOR RECONSIDERATION.— 
Any person whose request under subsection (b)
187 
is denied may, within 30 days of the denial, re-
quest reconsideration of the denial in accord-
ance with section 517A(b)— 
‘‘(i) based upon the submission of 
documents by such person; or 
‘‘(ii) based upon such documents and 
a meeting or teleconference. 
‘‘(B) RESPONSE.—Reconsideration of a 
designation determination under this paragraph 
shall be conducted in accordance with section 
517A(b). 
‘‘(5) WITHDRAWAL.—If the Secretary approves 
a priority review designation for a device under this 
section, the Secretary may not withdraw the des-
ignation based on the fact that the criteria specified 
in subsection (a) are no longer met because of the 
subsequent clearance or approval of another device 
that was designated under— 
‘‘(A) this section; or 
‘‘(B) section 515(d)(5) (as in effect imme-
diately prior to the enactment of the 21st Cen-
tury Cures Act). 
‘‘(d) PRIORITY REVIEW.—
188 
‘‘(1) ACTIONS.—For purposes of expediting the 
development and review of devices designated under 
subsection (c), the Secretary shall— 
‘‘(A) assign a team of staff, including a 
team leader with appropriate subject matter ex-
pertise and experience, for each device for 
which a request is submitted under subsection 
(b); 
‘‘(B) provide for oversight of the team by 
senior agency personnel to facilitate the effi-
cient development of the device and the efficient 
review of any submission described in sub-
section (b) for the device; 
‘‘(C) adopt an efficient process for timely 
dispute resolution; 
‘‘(D) provide for interactive communication 
with the sponsor of the device during the review 
process; 
‘‘(E) expedite the Secretary’s review of 
manufacturing and quality systems compliance, 
as applicable; 
‘‘(F) disclose to the sponsor in advance the 
topics of any consultation concerning the spon-
sor’s device that the Secretary intends to under-
take with external experts or an advisory com-
189 
mittee and provide the sponsor an opportunity 
to recommend such external experts; 
‘‘(G) for applications submitted under sec-
tion 515(c), provide for advisory committee 
input, as the Secretary determines appropriate 
(including in response to the request of the 
sponsor); and 
‘‘(H) assign staff to be available within a 
reasonable time to address questions posed by 
institutional review committees concerning the 
conditions and clinical testing requirements ap-
plicable to the investigational use of the device 
pursuant to an exemption under section 520(g). 
‘‘(2) ADDITIONAL ACTIONS.—In addition to the 
actions described in paragraph (1), for purposes of 
expediting the development and review of devices 
designated under subsection (c), the Secretary, in 
collaboration with the device sponsor, may, as appro-
priate— 
‘‘(A) coordinate with the sponsor regarding 
early agreement on a data development plan; 
‘‘(B) take steps to ensure that the design 
of clinical trials is as efficient as practicable, 
such as through adoption of shorter or smaller 
clinical 
trials, 
application 
of 
surrogate