Union Calendar No. 180
105TH CONGRESS
1ST SESSION
H. R. 1411
[Report No. 105–310]
A BILL
To amend the Federal Food, Drug, and Cosmetic
Act and the Public Health Service Act to facili-
tate the development and approval of new drugs
and biological products, and for other purposes.
OCTOBER 7, 1997
Reported with an amendment, committed to the Commit-
tee of the Whole House on the State of the Union, and
ordered to be printed
IB
Union Calendar No. 180
105TH CONGRESS
1ST SESSION
H. R. 1411
[Report No. 105–310]
To amend the Federal Food, Drug, and Cosmetic Act and the Public Health
Service Act to facilitate the development and approval of new drugs
and biological products, and for other purposes.
IN THE HOUSE OF REPRESENTATIVES
APRIL 23, 1997
Mr. BURR of North Carolina (for himself, Mr. GREENWOOD, Mr. BARTON of
Texas, Mr. KLUG, Mr. COBURN, and Mr. DEAL of Georgia) introduced
the following bill; which was referred to the Committee on Commerce
OCTOBER 7, 1997
Additional sponsors: Mr. THOMAS, Mr. UPTON, Mr. SOLOMON, Mr. HASTERT,
Mr. CANNON, Mr. DOOLEY of California, Ms. MCCARTHY of Missouri,
Mr. PRICE of North Carolina, Mr. BLILEY, Mr. INGLIS of South Caro-
lina, and Mr. MCHALE
OCTOBER 7, 1997
Reported with an amendment, committed to the Committee of the Whole
House on the State of the Union, and ordered to be printed
[Strike out all after the enacting clause and insert the part printed in italic]
[For text of introduced bill, see copy of bill as introduced on April 23, 1997]
A BILL
To amend the Federal Food, Drug, and Cosmetic Act and
the Public Health Service Act to facilitate the develop-
ment and approval of new drugs and biological products,
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; REFERENCES; TABLE OF CON-
TENTS.
(a) SHORT TITLE.—This Act may be cited as the ‘‘Pre-
scription Drug User Fee Reauthorization and Drug Regu-
latory Modernization Act of 1997’’.
(b) REFERENCES.—Except as otherwise specified,
whenever in this Act an amendment is expressed in terms
of an amendment to a section or other provision, the ref-
erence shall be considered to be made to that section or other
provision of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 321 et seq.).
(c) TABLE OF CONTENTS.—The table of contents for
this Act is as follows:
Sec. 1. Short title; references; table of contents.
Sec. 2. Fees relating to drugs.
Sec. 3. Pediatric studies of drugs.
Sec. 4. Expediting study and approval of fast track drugs.
Sec. 5. Expanded access to investigational therapies.
Sec. 6. Information program on clinical trials for serious or life-threatening dis-
eases.
Sec. 7. Dissemination of information on new uses.
Sec. 8. Studies and reports.
Sec. 9. Approval of supplemental applications for approved products.
Sec. 10. Health care economic information.
Sec. 11. Clinical investigations.
Sec. 12. Manufacturing changes for drugs.
Sec. 13. Streamlining clinical research on drugs.
Sec. 14. Data requirements for drugs.
Sec. 15. Content and review of applications.
Sec. 16. Scientific advisory panels.
Sec. 17. Dispute resolution.
Sec. 18. Informal agency statements.
Sec. 19. Positron emission tomography.
Sec. 20. Requirements for radiopharmaceuticals.
Sec. 21. Modernization of regulation.
Sec. 22. Pilot and small scale manufacture.
Sec. 23. Insulin and antibiotics.
Sec. 24. FDA mission and annual report.
Sec. 25. Information system.
Sec. 26. Education and training.
Sec. 27. Centers for education and research on drugs.
Sec. 28. Harmonization.
Sec. 29. Environmental impact review.
Sec. 30. National uniformity.
Sec. 31. FDA study of mercury compounds in drugs and food.
Sec. 32. Notification of discontinuance of a life saving product.
SEC. 2. FEES RELATING TO DRUGS.
(a) FINDINGS.—Congress finds that—
(1) prompt approval of safe and effective new
drugs and other therapies is critical to the improve-
ment of the public health so that patients may enjoy
the benefits provided by these therapies to treat and
prevent illness and disease;
(2) the public health will be served by making
additional funds available for the purpose of aug-
menting the resources of the Food and Drug Adminis-
tration that are devoted to the process for review of
human drug applications;
(3) the provisions added by the Prescription
Drug User Fee Act of 1992 have been successful in
substantially reducing review times for human drug
applications and should be—
(A) reauthorized for an additional 5 years,
with certain technical improvements; and
(B) carried out by the Food and Drug Ad-
ministration with new commitments to imple-
ment more ambitious and comprehensive im-
provements in regulatory processes of the Food
and Drug Administration; and
(4) the fees authorized by amendments made in
this title will be dedicated toward expediting the drug
development process and the review of human drug
applications as set forth in the goals identified in the
letters of lllllll , and lllllll ,
from the Secretary of Health and Human Services to
the chairman of the Committee on Commerce of the
House of Representatives and the chairman of the
Committee on Labor and Human Resources of the
Senate, as set forth at ll Cong. Rec. llll
(daily ed. lllll , 1997).
(b) DEFINITIONS.—Section 735 (21 U.S.C. 379g) is
amended—
(1) in the second sentence of paragraph (1)—
(A) by striking ‘‘Service Act, and’’ and in-
serting ‘‘Service Act,’’; and
(B) by striking ‘‘September 1, 1992.’’ and
inserting the following: ‘‘September 1, 1992, does
not include an application for a licensure of a
biological product for further manufacturing use
only, and does not include an application or
supplement submitted by a State or Federal Gov-
ernment entity for a drug that is not distributed
commercially. Such term does include an appli-
cation for licensure, as described in subpara-
graph (D), of a large volume biological product
intended for single dose injection for intravenous
use or infusion.’’;
(2) in the second sentence of paragraph (3)—
(A) by striking ‘‘Service Act, and’’ and in-
serting ‘‘Service Act,’’; and
(B) by striking ‘‘September 1, 1992.’’ and
inserting the following: ‘‘September 1, 1992, does
not include a biological product that is licensed
for further manufacturing use only, and does not
include a drug that is not distributed commer-
cially and is the subject of an application or
supplement submitted by a State or Federal Gov-
ernment entity. Such term does include a large
volume biological product intended for single
dose injection for intravenous use or infusion.’’;
(3) in paragraph (4), by striking ‘‘without’’ and
inserting ‘‘without substantial’’;
(4) by amending the first sentence of paragraph
(5) to read as follows:
‘‘(5) The term ‘prescription drug establishment’
means a foreign or domestic place of business which
is at one general physical location consisting of one
or more buildings all of which are within 5 miles of
each other and at which one or more prescription
drug products are manufactured in final dosage
form.’’.
(5) in paragraph (7)(A)—
(A) by striking ‘‘employees under contract’’
and all that follows through ‘‘Administration,’’
the second time it occurs and inserting ‘‘contrac-
tors of the Food and Drug Administration,’’; and
(B) by striking ‘‘and committees,’’ and in-
serting ‘‘and committees and to contracts with
such contractors,’’;
(6) in paragraph (8)—
(A) in subparagraph (A)—
(i) by striking ‘‘August of ’’ and insert-
ing ‘‘April of ’’; and
(ii) by striking ‘‘August 1992’’ and in-
serting ‘‘April 1997’’;
(B) in subparagraph (B), by striking
‘‘1992’’ and inserting ‘‘1997’’; and
(C) by striking the second sentence; and
(7) by adding at the end the following:
‘‘(9) The term ‘affiliate’ means a business entity
that has a relationship with a second business entity
if, directly or indirectly—
‘‘(A) one business entity controls, or has the
power to control, the other business entity; or
‘‘(B) a third party controls, or has power to
control, both of the business entities.’’.
(c) AUTHORITY TO ASSESS AND USE DRUG FEES.—
(1) TYPES OF FEES.—Section 736(a) (21 U.S.C.
379h(a)) is amended—
(A) by striking ‘‘Beginning in fiscal year
1993’’ and inserting ‘‘Beginning in fiscal year
1998’’;
(B) in paragraph (1)—
(i) by striking subparagraph (B) and
inserting the following:
‘‘(B) PAYMENT.—The fee required by sub-
paragraph (A) shall be due upon submission of
the application or supplement.’’;
(ii) in subparagraph (D)—
(I) in the subparagraph heading,
by striking ‘‘NOT ACCEPTED’’ and in-
serting ‘‘REFUSED’’;
(II) by striking ‘‘50 percent’’ and
inserting ‘‘75 percent’’;
(III) by striking ‘‘subparagraph
(B)(i)’’ and inserting ‘‘subparagraph
(B)’’; and
(IV) by striking ‘‘not accepted’’
and inserting ‘‘refused’’; and
(iii) by adding at the end the follow-
ing:
‘‘(E) EXCEPTION FOR DESIGNATED ORPHAN
DRUG OR INDICATION.—A human drug applica-
tion for a prescription drug product that has
been designated as a drug for a rare disease or
condition pursuant to section 526 shall not be
subject to a fee under subparagraph (A), unless
the human drug application includes indications
for other than rare diseases or conditions. A sup-
plement proposing to include a new indication
for a rare disease or condition in a human drug
application shall not be subject to a fee under
subparagraph (A), if the drug has been des-
ignated pursuant to section 526 as a drug for a
rare disease or condition with regard to the indi-
cation proposed in such supplement.
‘‘(F) EXCEPTION
FOR
SUPPLEMENTS
FOR
PEDIATRIC
INDICATIONS.—A supplement to a
human drug application for an indication for
use in pediatric populations shall not be assessed
a fee under subparagraph (A).
‘‘(G) REFUND
OF
FEE
IF
APPLICATION
WITHDRAWN.—If an application or supplement
is withdrawn after the application or supple-
ment is filed, the Secretary may waive and re-
fund the fee or a portion of the fee if no substan-
tial work was performed on the application or
supplement after the application or supplement
was filed. The Secretary shall have the sole dis-
cretion to waive and refund a fee or a portion
of the fee under this subparagraph. A determina-
tion by the Secretary concerning a waiver or re-
fund under this paragraph shall not be
reviewable.’’;
(C) by striking paragraph (2) and inserting
in lieu the following:
‘‘(2) 
PRESCRIPTION
DRUG
ESTABLISHMENT
FEE.—
‘‘(A) IN GENERAL.—Except as provided in
subparagraph (B), each person that is named as
the applicant in a human drug application, and
after September 1, 1992, had pending before the
Secretary a human drug application or supple-
ment, shall be assessed an annual fee established
in subsection (b) for each prescription drug es-
tablishment listed in its approved human drug
application as an establishment that manufac-
tures the prescription drug product named in the
application. The annual establishment fee shall
be assessed in each fiscal year in which the pre-
scription drug product named in the application
is assessed a fee under paragraph (3) unless the
prescription drug establishment listed in the ap-
plication does not engage in the manufacture of
the prescription drug product during the fiscal
year. The establishment fee shall be payable on
or before January 31 of each year. Each such es-
tablishment shall be assessed only one fee per es-
tablishment, notwithstanding the number of pre-
scription drug products manufactured at the es-
tablishment. In the event an establishment is
listed in a human drug application by more
than 1 applicant, the establishment fee for the
fiscal year shall be divided equally and assessed
among the applicants whose prescription drug
products are manufactured by the establishment
during the fiscal year and assessed product fees
under paragraph (3).
‘‘(B) EXCEPTION.—If, during the fiscal
year, an applicant initiates or causes to be initi-
ated the manufacture of a prescription drug
product at an establishment listed in its human
drug application—
‘‘(i) that did not manufacture the
product in the previous fiscal year; and
‘‘(ii) for which the full establishment
fee has been assessed in the fiscal year at a
time before manufacture of the prescription
drug product was begun;
the applicant will not be assessed a share of the
establishment fee for the fiscal year in which the
manufacture of the product began.’’.
(D) in paragraph (3)—
(i) in subparagraph (A)—
(I) in clause (i), by striking ‘‘is
listed’’ and inserting ‘‘has been submit-
ted for listing’’; and
(II) by striking ‘‘Such fee shall be
paid’’ and all that follows through
‘‘section 510.’’ and inserting the follow-
ing: ‘‘Such fee shall be payable for the
fiscal year in which the product is first
submitted for listing under section 510,
or for relisting under section 510 if the
product has been withdrawn from list-
ing and relisted. After such fee is paid
for that fiscal year, such fee shall be
payable on or before January 31 of
each year. Such fee shall be paid only
once for each product for a fiscal year
in which the fee is payable.’’; and
(ii) in subparagraph (B), by striking
‘‘505(j).’’ 
and 
inserting 
the 
following:
‘‘505(j), under an abbreviated application
filed under section 507, or under an abbre-
viated new drug application pursuant to
regulations in effect prior to the implemen-
tation of the Drug Price Competition and
Patent Term Restoration Act of 1984.’’.
(2) FEE AMOUNTS.—Section 736(b) (21 U.S.C.
379h(b)) is amended to read as follows:
‘‘(b) FEE AMOUNTS.—Except as provided in sub-
sections (c), (d), (f), and (g), the fees required under sub-
section (a) shall be determined and assessed as follows:
‘‘(1) APPLICATION AND SUPPLEMENT FEES.—
‘‘(A) FULL
FEES.—The application fee
under subsection (a)(1)(A)(i) shall be $250,704
in fiscal year 1998, $256,338 in each of fiscal
years 1999 and 2000, $267,606 in fiscal year
2001, and $258,451 in fiscal year 2002.
‘‘(B) OTHER
FEES.—The fee under sub-
section (a)(1)(A)(ii) shall be $125,352 in fiscal
year 1998, $128,169 in each of fiscal years 1999
and 2000, $133,803 in fiscal year 2001, and
$129,226 in fiscal year 2002.
‘‘(2) FEE
REVENUES
FOR
ESTABLISHMENT
FEES.—The total fee revenues to be collected in estab-
lishment fees under subsection (a)(2) shall be
$35,600,000 in fiscal year 1998, $36,400,000 in each
of fiscal years 1999 and 2000, $38,000,000 in fiscal
year 2001, and $36,700,000 in fiscal year 2002.
‘‘(3) TOTAL
FEE
REVENUES
FOR
PRODUCT
FEES.—The total fee revenues to be collected in prod-
uct fees under subsection (a)(3) in a fiscal year shall
be equal to the total fee revenues collected in establish-
ment fees under subsection (a)(2) in that fiscal year.’’.
(3) INCREASES
AND
ADJUSTMENTS.—Section
736(c) (21 U.S.C. 379h(c)) is amended—
(A) in the subsection heading, by striking
‘‘INCREASES AND’’;
(B) in paragraph (1)—
(i) by striking ‘‘(1) REVENUE’’ and all
that follows through ‘‘increased by the Sec-
retary’’ and inserting the following: ‘‘(1) IN-
FLATION ADJUSTMENT.—The fees and total
fee revenues established in subsection (b)
shall be adjusted by the Secretary’’;
(ii) in subparagraph (A), by striking
‘‘increase’’ and inserting ‘‘change’’;
(iii) in subparagraph (B), by striking
‘‘increase’’ and inserting ‘‘change’’; and
(iv) by adding at the end the following
flush sentence:
‘‘The adjustment made each fiscal year by this sub-
section will be added on a compounded basis to the
sum of all adjustments made each fiscal year after fis-
cal year 1997 under this subsection.’’;
(C) in paragraph (2), by striking ‘‘October
1, 1992,’’ and all that follows through ‘‘such
schedule.’’ and inserting the following: ‘‘Septem-
ber 30, 1997, adjust the establishment and prod-
uct fees described in subsection (b) for the fiscal
year in which the adjustment occurs so that the
revenues collected from each of the categories of
fees described in paragraphs (2) and (3) of sub-
section (b) shall be set to be equal to the revenues
collected from the category of application and
supplement fees described in paragraph (1) of
subsection (b).’’; and
(D) in paragraph (3), by striking ‘‘para-
graph (2)’’ and inserting ‘‘this subsection’’.
(4) 
FEE
WAIVER
OR
REDUCTION.—Section
736(d) (21 U.S.C. 379h(d)) is amended—
(A) by redesignating paragraphs (1), (2),
(3), and (4) as subparagraphs (A), (B), (C), and
(D), respectively and indenting appropriately;
(B) by striking ‘‘The Secretary shall grant
a’’ and all that follows through ‘‘finds that—’’
and inserting the following:
‘‘(1) IN GENERAL.—The Secretary shall grant a
waiver from or a reduction of one or more fees as-
sessed under subsection (a) where the Secretary finds
that—’’;
(C) in subparagraph (C) (as so redesignated
by subparagraph (A)), by striking ‘‘, or’’ and in-
serting a comma;
(D) in subparagraph (D) (as so redesig-
nated by subparagraph (A)), by striking the pe-
riod and inserting ‘‘, or’’;
(E) by inserting after subparagraph (D) (as
so redesignated by subparagraph (A)) the follow-
ing:
‘‘(E) the applicant is a small business sub-
mitting its first human drug application to the
Secretary for review.’’; and
(F) by striking ‘‘In making the finding in
paragraph (3),’’ and all that follows through
‘‘standard costs.’’ and inserting the following:
‘‘(2) USE OF STANDARD COSTS.—In making the
finding in paragraph (1)(C), the Secretary may use
standard costs.
‘‘(3) RULES RELATING TO SMALL BUSINESSES.—
‘‘(A) DEFINITION.—In paragraph (1)(E),
the term ‘small business’ means an entity that
has fewer than 500 employees, including employ-
ees of affiliates.
‘‘(B) WAIVER OF APPLICATION FEE.—The
Secretary shall waive under paragraph (1)(E)
the application fee for the first human drug ap-
plication that a small business or its affiliate
submits to the Secretary for review. After a small
business or its affiliate is granted such a waiver,
the small business or its affiliate shall pay—
‘‘(i) application fees for all subsequent
human drug applications submitted to the
Secretary for review in the same manner as
an entity that does not qualify as a small
business; and
‘‘(ii) all supplement fees for all supple-
ments to human drug applications submit-
ted to the Secretary for review in the same
manner as an entity that does not qualify
as a small business.’’.
(5) ASSESSMENT
OF
FEES.—Section 736(f)(1)
(21 U.S.C. 379h(f)(1)) is amended—
(A) by striking ‘‘fiscal year 1993’’ and in-
serting ‘‘fiscal year 1997’’; and
(B) by striking ‘‘fiscal year 1992’’ and in-
serting ‘‘fiscal year 1997 (excluding the amount
of fees appropriated for such fiscal year)’’.
(6) CREDITING AND AVAILABILITY OF FEES.—
Section 736(g) (21 U.S.C. 379h(g)) is amended—
(A) in paragraph (1), by adding at the end
the following: ‘‘Such sums as may be necessary
may be transferred from the Food and Drug Ad-
ministration salaries and expenses appropria-
tion account without fiscal year limitation to
such appropriation account for salaries and ex-
penses with such fiscal year limitation. The sums
transferred shall be available solely for the proc-
ess for the review of human drug applications
within the meaning of section 735(6).’’;
(B) in paragraph (2)—
(i) in subparagraph (A), by striking
‘‘Acts’’ and inserting ‘‘Acts, or otherwise
made available for obligation,’’; and
(ii) in subparagraph (B), by striking
‘‘over such costs for fiscal year 1992’’ and
inserting ‘‘over such costs, excluding costs
paid from fees collected under this section,
for fiscal year 1997’’; and
(C) by striking paragraph (3) and inserting
the following:
‘‘(3) AUTHORIZATION
OF
APPROPRIATIONS.—
There is authorized to be appropriated for fees under
this section—
‘‘(A) $106,800,000 for fiscal year 1998;
‘‘(B) $109,200,000 for fiscal year 1999;
‘‘(C) $109,200,000 for fiscal year 2000;
‘‘(D) $114,000,000 for fiscal year 2001; and
‘‘(E) $110,100,000 for fiscal year 2002,
as adjusted to reflect adjustments in the total fee reve-
nues made under this section and changes in the total
amounts collected by application, supplement, estab-
lishment, and product fees.
‘‘(4) OFFSET.—Any amount of fees collected for
a fiscal year which exceeds the amount of fees speci-
fied in appropriation Acts for such fiscal year shall
be credited to the appropriation account of the Food
and Drug Administration as provided in paragraph
(1), and shall be subtracted from the amount of fees
that would otherwise be authorized to be collected
under appropriation Acts for a subsequent fiscal
year.’’.
(7) REQUIREMENT FOR WRITTEN REQUESTS FOR
WAIVERS, REDUCTIONS, AND FEES.—Section 736 (21
U.S.C. 379h) is amended—
(A) by redesignating subsection (i) as sub-
section (j); and
(B) by inserting after subsection (h) the fol-
lowing:
‘‘(i) WRITTEN REQUESTS FOR WAIVERS, REDUCTIONS,
AND REFUNDS.—To qualify for consideration for a waiver
or reduction under subsection (d), or for a refund of any
fee collected in accordance with subsection (a), a person
shall submit to the Secretary a written request for such
waiver, reduction, or refund not later than 180 days after
such fee is due.’’.
(8) SPECIAL RULE FOR WAIVER, REFUNDS, AND
EXCEPTIONS.—Any requests for waivers, refunds, or
exceptions for fees assessed prior to the date of enact-
ment of this Act shall be submitted in writing to the
Secretary of Health and Human Services within 1
year after the date of enactment of this Act.
(d) ANNUAL REPORTS.—
(1) PERFORMANCE
REPORT.—Beginning with
fiscal year 1998, not later than 60 days after the end
of each fiscal year during which fees are collected
under part 2 of subchapter C of chapter VII of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C.
379g et seq.), the Secretary of Health and Human
Services shall prepare and submit to the Committee
on Commerce of the House of Representatives and the
Committee on Labor and Human Resources of the
Senate a report concerning the progress of the Food
and Drug Administration in achieving the goals iden-
tified in the letter described in subsection (a)(4) dur-
ing such fiscal year and the future plans of the Food
and Drug Administration for meeting the goals.
(2) FISCAL REPORT.—Beginning with fiscal year
1998, not later than 120 days after the end of each
fiscal year during which fees are collected under the
part described in subsection (a), the Secretary of
Health and Human Services shall prepare and sub-
mit to the Committee on Commerce of the House of
Representatives and the Committee on Labor and
Human Resources of the Senate a report on the im-
plementation of the authority for such fees during
such fiscal year and the use, by the Food and Drug
Administration, of the fees collected during such fiscal
year for which the report is made.
(e) EFFECTIVE DATE.—The amendments made by this
section shall take effect October 1, 1997.
(f) TERMINATION OF EFFECTIVENESS.—The amend-
ments made by subsections (b) and (c) cease to be effective
October 1, 2002, and subsection (d) ceases to be effective
120 days after such date.
SEC. 3. PEDIATRIC STUDIES OF DRUGS.
Chapter V (21 U.S.C. 351 et seq.) is amended by in-
serting after section 505 the following:
‘‘PEDIATRIC STUDIES OF DRUGS
‘‘SEC. 505A. (a) MARKET EXCLUSIVITY
FOR NEW
DRUGS.—If, prior to approval of an application that is
submitted under section 505(b)(1), the Secretary determines
that information relating to the use of a drug in the pedi-
atric population may produce health benefits in that popu-
lation, the Secretary makes a written request for pediatric
studies (which shall include a timeframe for completing
such studies), and such studies are completed within any
such timeframe and the reports thereof submitted in accord-
ance with subsection (d)(2) or accepted in accordance with
subsection (d)(3)—
‘‘(1)(A) the period during which an application
may not be submitted under subsections (c)(3)(D)(ii)
and (j)(4)(D)(ii) of section 505 shall be five years and
six months rather than five years, and the references
in subsections (c)(3)(D)(ii) and (j)(4)(D)(ii) of sec-
tion 505 to four years, to forty-eight months, and to
seven and one-half years shall be deemed to be four
and one-half years, fifty-four months, and eight years,
respectively; or
‘‘(B) the period of market exclusivity under sub-
sections (c)(3)(D)(iii) and (iv) and (j)(4)(D)(iii) and
(iv) of section 505 shall be three years and six months
rather than three years; and
‘‘(2)(A) if the drug is the subject of—
‘‘(i) a listed patent for which a certification
has 
been 
submitted 
under 
subsections
(b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of section 505
and for which pediatric studies were submitted
prior to the expiration of the patent (including
any patent extensions); or
‘‘(ii) a listed patent for which a certifi-
cation has been submitted under subsections
(b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 505,
the period during which an application may not be
approved 
under 
section 
505(c)(3) 
or 
section
505(j)(4)(B) shall be extended by a period of six
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
sub-
mitted 
under 
subsection 
(b)(2)(A)(iv) 
or
(j)(2)(A)(vii)(IV) of section 505, and in the patent in-
fringement litigation resulting from the certification
the court determines that the patent is valid and
would be infringed, the period during which an appli-
cation may not be approved under section 505(c)(3)
or section 505(j)(4)(B) shall be extended by a period
of six months after the date the patent expires (in-
cluding any patent extensions).
‘‘(b) SECRETARY TO DEVELOP LIST OF DRUGS FOR
WHICH ADDITIONAL PEDIATRIC INFORMATION MAY BE
BENEFICIAL.—Not later than 180 days after the date of en-
actment of this section, the Secretary, after consultation
with experts in pediatric research shall develop, prioritize,
and publish an initial list of approved drugs for which ad-
ditional pediatric information may produce health benefits
in the pediatric population. The Secretary shall annually
update the list.
‘‘(c) MARKET EXCLUSIVITY FOR ALREADY-MARKETED
DRUGS.—If the Secretary makes a written request to the
holder of an approved application under section 505(b)(1)
for pediatric studies (which shall include a timeframe for
completing such studies) concerning a drug identified in the
list described in subsection (b), the holder agrees to the re-
quest, the studies are completed within any such timeframe
and the reports thereof are submitted in accordance with
subsection (d)(2) or accepted in accordance with subsection
(d)(3)—
‘‘(1)(A) the period during which an application
may not be submitted under subsection (c)(3)(D)(ii)
or (j)(4)(D)(ii) of section 505 shall be five years and
six months rather than five years, and the references
in subsections (c)(3)(D)(ii) and (j)(4)(D)(ii) of sec-
tion 505 to four years, to forty-eight months, and to
seven and one-half years shall be deemed to be four
and one-half years, fifty-four months, and eight years,
respectively; or
‘‘(B) the period of market exclusivity under sub-
sections (c)(3)(D)(iii) and (iv) and (j)(4)(D)(iii) and
(iv) of section 505 shall be three years and six months
rather than three years; and
‘‘(2)(A) if the drug is the subject of—
‘‘(i) a listed patent for which a certification
has been submitted under subsection (b)(2)(A)(ii)
or (j)(2)(A)(vii)(II) of section 505 and for which
pediatric studies were submitted prior to the ex-
piration of the patent (including any patent ex-
tensions); or
‘‘(ii) a listed patent for which a certifi-
cation has been submitted under subsection
(b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 505,
the period during which an application may not be
approved 
under 
section 
505(c)(3) 
or 
section
505(j)(4)(B) shall be extended by a period of six
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 section
505, and in the patent infringement litigation result-
ing from the certification the court determines that
the patent is valid and would be infringed, the period
during which an application may not be approved
under section 505(c)(3) or section 505(j)(4)(B) shall
be extended by a period of six months after the date
the patent expires (including any patent extensions).
‘‘(d) CONDUCT OF PEDIATRIC STUDIES.—
‘‘(1) AGREEMENT FOR STUDIES.—The Secretary
may, pursuant to a written request for studies, after
consultation with—
‘‘(A) the sponsor of an application for an
investigational new drug under section 505(i);
‘‘(B) the sponsor of an application for a
drug under section 505(b)(1); or
‘‘(C) the holder of an approved application
for a drug under section 505(b)(1),
agree with the sponsor or holder for the conduct of pe-
diatric studies for such drug.
‘‘(2) WRITTEN PROTOCOLS TO MEET THE STUD-
IES REQUIREMENT.—If the sponsor or holder and the
Secretary agree upon written protocols for the studies,
the studies requirement of subsection (a) or (c) is sat-
isfied upon the completion of the studies and submis-
sion of the reports thereof in accordance with the
original written request and the written agreement re-
ferred to in paragraph (1). Not later than 60 days
after the submission of the report of the studies, the
Secretary shall determine if such studies were or were
not conducted in accordance with the original written
request and the written agreement and reported in ac-
cordance with the requirements of the Secretary for
filing and so notify the sponsor or holder.
‘‘(3) OTHER METHODS TO MEET THE STUDIES
REQUIREMENT.—If the sponsor or holder and the Sec-
retary have not agreed in writing on the protocols for
the studies, the studies requirement of subsection (a)
or (c) is satisfied when such studies have been com-
pleted and the reports accepted by the Secretary. Not
later than 90 days after the submission of the reports
of the studies, the Secretary shall accept or reject such
reports and so notify the sponsor or holder. The Sec-
retary’s only responsibility in accepting or rejecting
the reports shall be to determine, within the 90 days,
whether the studies fairly respond to the written re-
quest, whether such studies have been conducted in ac-
cordance with commonly accepted scientific principles
and protocols, and whether such studies have been re-
ported in accordance with the requirements of the
Secretary for filing.
‘‘(e) DELAY OF EFFECTIVE DATE FOR CERTAIN APPLI-
CATIONS; PERIOD OF MARKET EXCLUSIVITY.—If the Sec-
retary determines that the acceptance or approval of an ap-
plication under section 505(b)(2) or 505(j) for a drug may
occur after submission of reports of pediatric studies under
this section, which were submitted prior to the expiration
of the patent (including any patent extension) or market
exclusivity protection, but before the Secretary has deter-
mined whether the requirements of subsection (d) have been
satisfied, the Secretary shall delay the acceptance or ap-
proval under section 505(b)(2) or 505(j), respectively, until
the determination under subsection (d) is made, but such
delay shall not exceed 90 days. In the event that require-
ments of this section are satisfied, the applicable period of
market exclusivity referred to in subsection (a) or (c) shall
be deemed to have been running during the period of delay.
‘‘(f) NOTICE OF DETERMINATIONS ON STUDIES RE-
QUIREMENT.—The Secretary shall publish a notice of any
determination that the requirements of subsection (d) have
been met and that submissions and approvals under section
505(b)(2) or (j) for a drug will be subject to the provisions
of this section.
‘‘(g) DEFINITIONS.—As used in this section, the term
‘pediatric studies’ or ‘studies’ means at least one clinical
investigation (that, at the Secretary’s discretion, may in-
clude pharmacokinetic studies) in pediatric age groups in
which a drug is anticipated to be used.
‘‘(h) LIMITATION.—The holder of an approved applica-
tion for a new drug that has already received six months
of market exclusivity under subsection (a) or (c) may, if
otherwise eligible, obtain six months of market exclusivity
under subsection (c)(1)(B) for a supplemental application,
except that the holder is not eligible for exclusivity under
subsection (c)(2).
‘‘(i) RELATIONSHIP
TO
REGULATIONS.—Notwith-
standing any other provision of law, if any pediatric study
is required pursuant to regulations promulgated by the Sec-
retary, such study shall be deemed to satisfy the requirement
for market exclusivity pursuant to this section.
‘‘(j) SUNSET.—No period of market exclusivity shall
be granted under this section based on studies commenced
after January 1, 2002. The Secretary shall conduct a study
and report to Congress not later than January 1, 2001,
based on the experience under the program. The study and
report shall examine all relevant issues, including—
‘‘(1) the effectiveness of the program in improv-
ing information about important pediatric uses for
approved drugs;
‘‘(2) the adequacy of the incentive provided
under this section;
‘‘(3) the economic impact of the program on tax-
payers and consumers, including the impact of the
lack of lower cost generic drugs on lower income pa-
tients; and
‘‘(4) any suggestions for modification that the
Secretary deems appropriate.’’.
SEC. 4. EXPEDITING STUDY AND APPROVAL OF FAST TRACK
DRUGS.
(a) IN GENERAL.—Chapter VII is amended by adding
at the end the following:
‘‘SUBCHAPTER D—FAST TRACK PRODUCTS
‘‘SEC. 741. FAST TRACK PRODUCTS.
‘‘(a) DESIGNATION OF DRUG AS A FAST TRACK PROD-
UCT.—
‘‘(1) IN GENERAL.—The Secretary shall facilitate
the development and expedite the review of new drugs
that are intended for the treatment of serious or life-
threatening conditions and that demonstrate the po-
tential to address unmet medical needs for such con-
ditions. In this section, such products shall be known
as ‘fast track products’.
‘‘(2) REQUEST FOR DESIGNATION.—The sponsor
of a drug may request the Secretary to designate the
drug as a fast track product. A request for the des-
ignation may be made concurrently with, or at any
time after, submission of an application for the inves-
tigation of the drug under section 505(i) or section
351(a)(4) of the Public Health Service Act.
‘‘(3) DESIGNATION.—Within 30 calendar days
after the receipt of a request under paragraph (2), the
Secretary shall determine whether the drug that is the
subject of the request meets the criteria described in
paragraph (1). If the Secretary finds that the drug
meets the criteria, the Secretary shall designate the
drug as a fast track product and shall take such ac-
tions as are appropriate to expedite the development
and review of the application for approval of such
product.
‘‘(b) APPROVAL OF APPLICATION FOR A FAST TRACK
PRODUCT.—
‘‘(1) IN GENERAL.—The Secretary may approve
an application for approval of a fast track product
under section 505(b) or section 351 of the Public
Health Service Act (21 U.S.C. 262) upon a deter-
mination that the product has an effect on a clinical
endpoint or a surrogate endpoint that is reasonably
likely to predict clinical benefit.
‘‘(2) LIMITATION.—Approval of a fast track
product under this subsection may be subject to the
requirements—
‘‘(A) that the sponsor conduct appropriate
post-approval studies to validate the surrogate
endpoint or otherwise confirm the effect on the
clinical endpoint; and
‘‘(B) that the sponsor submit copies of all
promotional materials related to the fast track
product during the preapproval review period
and, following approval and for such period
thereafter as the Secretary deems appropriate, at
least 30 days prior to dissemination of the mate-
rials.
‘‘(3) EXPEDITED WITHDRAWAL OF APPROVAL.—
The Secretary may withdraw approval of a fast track
product using expedited procedures (as prescribed by
the Secretary in regulations which shall include an
opportunity for an informal hearing), if—
‘‘(A) the sponsor fails to conduct any re-
quired post-approval study of the fast track drug
with due diligence;
‘‘(B) a post-approval study of the fast track
product fails to verify clinical benefit of the
product;
‘‘(C) other evidence demonstrates that the
fast track product is not safe or effective under
the conditions of use; or
‘‘(D) the sponsor disseminates false or mis-
leading promotional materials with respect to
the product.
‘‘(c) REVIEW OF INCOMPLETE APPLICATIONS FOR AP-
PROVAL OF A FAST TRACK PRODUCT.—
‘‘(1) IN GENERAL.—If the Secretary determines,
after preliminary evaluation of clinical data submit-
ted by the sponsor, that a fast track product may be
effective the Secretary shall evaluate for filing, and
may commence review of portions of, an application
for the approval of the product before the sponsor sub-
mits a complete application. The Secretary shall com-
mence such review only if the applicant (A) provides
a schedule for submission of information necessary to
make the application complete, and (B) pays any fee
that may be required under section 736.
‘‘(2) EXCEPTION.—Any time period for review of
human drug applications that has been agreed to by
the Secretary and that has been set forth in goals
identified in letters of the Secretary (relating to the
use of fees collected under section 736 to expedite the
drug development process and the review of human
drug applications) shall not apply to an application
submitted under paragraph (1) until the date on
which the application is complete.
‘‘(d) AWARENESS EFFORTS.—The Secretary shall—
‘‘(1) develop and disseminate to physicians, pa-
tient organizations, pharmaceutical and biotechnology
companies, and other appropriate persons a descrip-
tion of the provisions applicable to fast track products
established under this section; and
‘‘(2) establish a program to encourage the devel-
opment of surrogate endpoints that are reasonably
likely to predict clinical benefit for serious or life-
threatening conditions for which there exist signifi-
cant unmet medical needs.’’.
(b) GUIDANCE.—Within 1 year after the date of enact-
ment of this Act, the Secretary shall issue guidance for fast
track products (as defined in section 741(a)(1) of the Fed-
eral Food, Drug, and Cosmetic Act) that describes the poli-
cies and procedures that pertain to section 741 of such Act.
SEC. 5. EXPANDED ACCESS TO INVESTIGATIONAL THERA-
PIES.
Chapter V (21 U.S.C. 351 et seq.) is amended by add-
ing at the end the following:
‘‘SUBCHAPTER D—UNAPPROVED THERAPIES AND
DIAGNOSTICS
‘‘SEC. 551. EXPANDED ACCESS TO UNAPPROVED THERAPIES
AND DIAGNOSTICS.
‘‘(a) EMERGENCY SITUATIONS.—The Secretary may,
under appropriate conditions determined by the Secretary,
authorize the shipment of investigational drugs (as defined
in regulations prescribed by the Secretary) for the diagnosis
or treatment of a serious disease or condition in emergency
situations.
‘‘(b) INDIVIDUAL PATIENT ACCESS
TO INVESTIGA-
TIONAL PRODUCTS INTENDED FOR SERIOUS DISEASES.—
Any person, acting through a physician licensed in accord-
ance with State law, may request from a manufacturer or
distributor, and any manufacturer or distributor may pro-
vide to such physician after compliance with the provisions
of this subsection, an investigational drug (as defined in
regulations prescribed by the Secretary) for the diagnosis
or treatment of a serious disease or condition if—
‘‘(1) the licensed physician determines that the
person has no comparable or satisfactory alternative
therapy available to diagnose or treat the disease or
condition involved, and that the risk to the person
from the investigational drug is not greater than the
risk from the disease or condition;
‘‘(2) the Secretary determines that there is suffi-
cient evidence of safety and effectiveness to support
the use of the investigational drug in the case de-
scribed in paragraph (1);
‘‘(3) the Secretary determines that provision of
the investigational drug will not interfere with the
initiation, conduct, or completion of clinical inves-
tigations to support marketing approval; and
‘‘(4) the sponsor, or clinical investigator, of the
investigational drug submits to the Secretary a clini-
cal protocol consistent with the provisions of section
505(i) and any regulations promulgated under section
505(i) describing the use of investigational drugs in
a single patient or a small group of patients.
‘‘(c) TREATMENT INDS.—Upon submission by a spon-
sor or a physician of a protocol intended to provide wide-
spread access to an investigational drug for eligible pa-
tients, the Secretary shall permit such investigational drug
to be made available for expanded access under a treatment
investigational new drug application if the Secretary deter-
mines that—
‘‘(1) under the treatment investigational new
drug application, the investigational drug is intended
for use in the diagnosis or treatment of a serious or
immediately life-threatening disease or condition;
‘‘(2) there is no comparable or satisfactory alter-
native therapy available to diagnose or treat that
stage of disease or condition in the population of pa-
tients to which the investigational drug is intended to
be administered;
‘‘(3)(A) the investigational drug is under inves-
tigation in a controlled clinical trial for the use de-
scribed in paragraph (1) under an effective investiga-
tional new drug application; or
‘‘(B) all clinical trials necessary for approval of
that use of the investigational drug have been com-
pleted;
‘‘(4) the sponsor of the controlled clinical trials
is actively pursuing marketing approval of the inves-
tigational drug for the use described in paragraph (1)
with due diligence;
‘‘(5) the provision of the investigational drug
will not interfere with the enrollment of patients in
ongoing clinical investigations under section 505(i);
‘‘(6) in the case of serious diseases, there is suffi-
cient evidence of safety and effectiveness to support
the use described in paragraph (1); and
‘‘(7) in the case of immediately life-threatening
diseases, the available scientific evidence, taken as a
whole, provides a reasonable basis to conclude that the
product may be effective for its intended use and
would not expose patients to an unreasonable and sig-
nificant risk of illness or injury.
A protocol submitted under this subsection shall be subject
to the provisions of section 505(i) and regulations promul-
gated under section 505(i). The Secretary may inform na-
tional, State, and local medical associations and societies,
voluntary health associations, and other appropriate per-
sons about the availability of an investigational drug under
expanded access protocols submitted under this subsection.
The information provided by the Secretary, in accordance
with the preceding sentence, shall be of the same type of
information that is required by section 402(j)(3) of the Pub-
lic Health Service Act.
‘‘(d) TERMINATION.—The Secretary may, at any time,
with respect to a sponsor, physician, manufacturer, or dis-
tributor described in this section, terminate expanded access
provided under this section for an investigational drug if
the requirements under this section are no longer met.’’.
SEC. 6. INFORMATION PROGRAM ON CLINICAL TRIALS FOR
SERIOUS OR LIFE-THREATENING DISEASES.
(a) IN GENERAL.—Section 402 of the Public Health
Service Act (42 U.S.C. 282) is amended—
(1) by redesignating subsections (j) and (k) as
subsections (k) and (l), respectively; and
(2) by inserting after subsection (i), the follow-
ing:
‘‘(j)(1) The Secretary, acting through the Director of
the National Institutes of Health, shall establish, maintain,
and operate a program with respect to information on re-
search relating to the treatment, detection, and prevention
of serious or life-threatening diseases and conditions. The
program shall, with respect to the agencies of the Depart-
ment of Health and Human Services, be integrated and co-
ordinated, and, to the extent practicable, coordinated with
other data banks containing similar information.
‘‘(2)(A) After consultation with the Commissioner of
Food and Drugs, the directors of the appropriate agencies
of the National Institutes of Health (including the National
Library of Medicine), and the Director of the Centers for
Disease Control and Prevention, the Secretary shall, in car-
rying out paragraph (1), establish a data bank of informa-
tion on clinical trials for drugs for serious or life-threaten-
ing diseases and conditions.
‘‘(B) In carrying out subparagraph (A), the Secretary
shall collect, catalog, store, and disseminate the information
described in such subparagraph. The Secretary shall dis-
seminate such information through information systems,
which shall include toll-free telephone communications,
available to individuals with serious or life-threatening dis-
eases and conditions, to other members of the public, to
health care providers, and to researchers.
‘‘(3) The data bank shall include the following:
‘‘(A) A registry of clinical trials (whether feder-
ally or privately funded) of experimental treatments
for serious or life-threatening diseases and conditions
under regulations promulgated pursuant to sections
505 of the Federal Food, Drug, and Cosmetic Act that
provides a description of the purpose of each experi-
mental drug, either with the consent of the protocol
sponsor, or when a trial to test effectiveness begins.
Information provided shall consist of eligibility cri-
teria, a description of the location of trial sites, and
a point of contact for those wanting to enroll in the
trial, and shall be in a form that can be readily un-
derstood by members of the public. Such information
must be forwarded to the data bank by the sponsor
of the trial not later than 21 days after trials to test
clinical effectiveness have begun.
‘‘(B) Information pertaining to experimental
treatments for serious or life-threatening diseases and
conditions that may be available—
‘‘(i) under a treatment investigational new
drug application that has been submitted to the
Food and Drug Administration under section
551(c) of the Federal Food, Drug, and Cosmetic
Act; or
‘‘(ii) as a Group C cancer drug (as defined
by the National Cancer Institute).
The data bank may also include information pertain-
ing to the results of clinical trials of such treatments,
with the consent of the sponsor, including information
concerning potential toxicities or adverse effects asso-
ciated with the use or administration of such experi-
mental treatments.
‘‘(4) The data bank shall not include information re-
lating to an investigation if the sponsor has provided a de-
tailed certification to the Secretary that disclosure of such
information would substantially interfere with the timely
enrollment of subjects in the investigation, unless the Sec-
retary, after the receipt of the certification, provides the
sponsor with a detailed written determination that such
disclosure would not substantially interfere with such en-
rollment.
‘‘(5) For the purpose of carrying out this subsection,
there are authorized to be appropriated such sums as may
be necessary. Fees collected under section 736 of the Federal
Food, Drug, and Cosmetic Act shall not be used in carrying
out this subsection.’’.
(b) COLLABORATION AND REPORT.—
(1) IN GENERAL.—The Secretary of Health and
Human Services, the Director of the National Insti-
tutes of Health, and the Commissioner of Food and
Drugs shall collaborate to determine the feasibility of
including device investigations within the scope of the
registry requirements set forth in section 402(j) of the
Public Health Service Act.
(2) REPORT.—Not later than 2 years after the
date of enactment of this section, the Secretary of
Health and Human Services shall prepare and sub-
mit to the Committee on Labor and Human Re-
sources of the Senate and the Committee on Commerce
of the House of Representatives a report—
(A) of the public health need, if any, for in-
clusion of device investigations within the scope
of the registry requirements set forth in section
402(j) of the Public Health Service Act;
(B) on the adverse impact, if any, on device
innovation and research in the United States if
information relating to such device investigation
is required to be publicly disclosed; and
(C) on such other issues relating to such sec-
tion 402(j) as the Secretary may deem appro-
priate.
SEC. 7. DISSEMINATION OF INFORMATION ON NEW USES.
(a) IN GENERAL.—Chapter VII (21 U.S.C. 371 et
seq.), as amended by section 4, is amended by adding at
the end the following:
‘‘SUBCHAPTER E—DISSEMINATION OF TREATMENT
INFORMATION
‘‘SEC. 745. REQUIREMENTS FOR DISSEMINATION OF TREAT-
MENT INFORMATION ON DRUGS.
‘‘(a) IN GENERAL.—Notwithstanding sections 301(d),
502(f), and 505 and section 351 of the Public Health Serv-
ice Act (42 U.S.C. 262), a manufacturer may disseminate
to—
‘‘(1) a health care practitioner,
‘‘(2) a pharmacy benefit manager,
‘‘(3) a health insurance issuer,
‘‘(4) a group health plan, or
‘‘(5) a Federal or State governmental agency,
written information concerning the safety, effectiveness, or
benefit of a use not described in the approved labeling of
a drug if the manufacturer meets the requirements of sub-
section (b).
‘‘(b) SPECIFIC REQUIREMENTS.—A manufacturer may
disseminate information about a new use of a drug under
subsection (a) only if—
‘‘(1) there is in effect for such drug an applica-
tion filed under section 505(b) or a biologics license
issued under section 351 of the Public Health Service
Act;
‘‘(2) the information meets the requirements of
section 746;
‘‘(3) the information to be disseminated is not
derived from clinical research conducted by another
manufacturer or if it was derived from research con-
ducted by another manufacturer, the manufacturer
disseminating the information has the permission of
such other manufacturer to make the dissemination;
‘‘(4) the manufacturer has, 60 days before such
dissemination, submitted to the Secretary—
‘‘(A) a copy of the information dissemi-
nated; and
‘‘(B) any clinical trial information the
manufacturer has relating to the safety or effec-
tiveness of the new use, any reports of clinical
experience pertinent to the safety of the new use,
and a summary of such information;
‘‘(5) the manufacturer has complied with the re-
quirements of section 748 (relating to certification
that the manufacturer will submit a supplemental ap-
plication with respect to such use);
‘‘(6) the manufacturer agrees to include along
with the information disseminated under this sub-
section—
‘‘(A) a prominently displayed statement
that discloses—
‘‘(i) that the information concerns a
use of a drug that has not been approved by
the Food and Drug Administration;
‘‘(ii) if applicable, that the informa-
tion is being disseminated at the expense of
the manufacturer;
‘‘(iii) if applicable, the name of any
authors of the information who are employ-
ees of, consultants to, or have received com-
pensation from, the manufacturer, or who
have a significant financial interest in the
manufacturer;
‘‘(iv) the official labeling for the drug
and all updates with respect to the labeling;
‘‘(v) if applicable, a statement that
there are products or treatments that have
been approved for the use that is the subject
of the information being disseminated pur-
suant to subsection (a)(1); and
‘‘(vi) the identification of any person
that has provided funding for the conduct of
a study relating to the new use of a drug
for which such information is being dis-
seminated; and
‘‘(B) a bibliography of other articles from a
scientific reference publication or scientific or
medical journal that have been previously pub-
lished about the such use of the drug covered by
the information disseminated (unless the infor-
mation already includes such bibliography).
‘‘(c) ADDITIONAL INFORMATION.—If the Secretary de-
termines, after providing notice of such determination and
an opportunity for a meeting with respect to such deter-
mination, that the information submitted by a manufac-
turer under subsection (b)(3)(B), with respect to the use of
a drug for which the manufacturer is disseminating infor-
mation, fails to provide data, analyses, or other written
matter that is objective and balanced, the Secretary may
require the manufacturer to disseminate—
‘‘(1) additional objective and scientifically sound
information that pertains to the safety or effectiveness
of the use and is necessary to provide objectivity and
balance, including any information that the manufac-
turer has submitted to the Secretary or, where appro-
priate, a summary of such information or any other
information that the Secretary has authority to make
available to the public; and
‘‘(2) an objective statement of the Secretary,
based on data or other scientifically sound informa-
tion available to the Secretary, that bears on the safe-
ty or effectiveness of the new use of the drug.
‘‘SEC. 746. INFORMATION AUTHORIZED TO BE DISSEMI-
NATED.
‘‘(a) AUTHORIZED INFORMATION.—A manufacturer
may disseminate the information on the new use of a drug
under section 745 only if the information—
‘‘(1) is in the form of an unabridged—
‘‘(A) reprint or copy of an article, peer-re-
viewed by experts qualified by scientific training
or experience to evaluate the safety or effective-
ness of the drug, which was published in a sci-
entific or medical journal (as defined in section
750(6)), which is about a clinical investigation
with respect to the drug, and which would be
considered to be scientifically sound by such ex-
perts; or
‘‘(B) reference publication, described in sub-
section (b), that includes information about a
clinical investigation with respect to the drug
that would be considered to be scientifically
sound by experts qualified by scientific training
or experience to evaluate the safety or effective-
ness of the drug that is the subject of such a clin-
ical investigation; and
‘‘(2) is not false or misleading and would not
pose a significant risk to the public health.
‘‘(b) REFERENCE PUBLICATION.—A reference publica-
tion referred to in subsection (a)(1)(B) is a publication
that—
‘‘(1) has not been written, edited, excerpted, or
published specifically for, or at the request of, a man-
ufacturer of a drug;
‘‘(2) has not been edited or significantly influ-
enced by a such a manufacturer;
‘‘(3) is not solely distributed through such a
manufacturer but is generally available in bookstores
or other distribution channels where medical textbooks
are sold;
‘‘(4) does not focus on any particular drug of a
manufacturer that disseminates information under
section 745 and does not have a primary focus on
new uses of drugs that are marketed or under inves-
tigation by a manufacturer supporting the dissemina-
tion of information; and
‘‘(5) presents materials that are not false or mis-
leading.
‘‘SEC. 747. ESTABLISHMENT OF LIST OF ARTICLES AND PUB-
LICATIONS DISSEMINATED AND LIST OF PRO-
VIDERS THAT RECEIVED ARTICLES AND REF-
ERENCE PUBLICATIONS.
‘‘(a) IN GENERAL.—A manufacturer may disseminate
information under section 745 only if the manufacturer
prepares and submits to the Secretary biannually—
‘‘(1) a list containing the titles of the articles
and reference publications relating to the new use of
drugs that were disseminated by the manufacturer to
a person described in section 745(a) for the 6-month
period preceding the date on which the manufacturer
submits the list to the Secretary; and
‘‘(2) a list that identifies the categories of provid-
ers (as described in section 745(a)) that received the
articles and reference publications for the 6-month pe-
riod described in paragraph (1).
‘‘(b) RECORDS.—A manufacturer that disseminates
information under section 745 shall keep records that may
be used by the manufacturer when, pursuant to section 749,
such manufacturer is required to take corrective action and
shall be made available to the Secretary, upon request, for
purposes of ensuring or taking corrective action pursuant
to such section. Such records, at the Secretary’s discretion,
may identify the recipient of information provided pursu-
ant to section 745 or the categories of such recipients.
‘‘SEC. 748. REQUIREMENT REGARDING SUBMISSION OF SUP-
PLEMENTAL APPLICATION FOR NEW USE; EX-
EMPTION FROM REQUIREMENT.
‘‘(a) IN GENERAL.—A manufacturer may disseminate
information under section 745 on a new use only if—
‘‘(1) the manufacturer meets the condition de-
scribed in subsection (b) or in subsection (c); or
‘‘(2) there is in effect for the manufacturer an ex-
emption under subsection (d) from the requirement of
paragraph (1).
‘‘(b) SUPPLEMENTAL APPLICATION; CONDITION
IN
CASE
OF COMPLETED STUDIES.—For purposes of sub-
section (a)(1), a manufacturer may disseminate informa-
tion on a new use if the manufacturer has submitted to
the Secretary an application containing a certification
that—
‘‘(1) the studies needed for the submission of a
supplemental application for the new use have been
completed; and
‘‘(2) the supplemental application will be sub-
mitted to the Secretary not later than 6 months after
the date of the initial dissemination of information
under section 745.
‘‘(c) SUPPLEMENTAL APPLICATION; CONDITION
IN
CASE OF PLANNED STUDIES.—
‘‘(1) IN GENERAL.—For purposes of subsection
(a)(1), a manufacturer may disseminate information
on a new use if—
‘‘(A) the manufacturer has submitted to the
Secretary an application containing—
‘‘(i) a proposed protocol and schedule
for conducting the studies needed for the
submission of a supplemental application
for the new use; and
‘‘(ii) a certification that the supple-
mental application will be submitted to the
Secretary not later than 36 months after the
date of the initial dissemination of informa-
tion under section 745 (or, as applicable,
not later than such date as the Secretary
may specify pursuant to an extension under
this paragraph or paragraph (3)); and
‘‘(B) the Secretary has determined that the
proposed protocol is adequate and that the sched-
ule for completing such studies is reasonable.
The Secretary may grant a longer period of time for
a manufacturer to submit a supplemental application
if the Secretary determines that the studies needed to
submit such an application cannot be completed and
submitted within 36 months.
‘‘(2) PROGRESS REPORTS ON STUDIES.—A man-
ufacturer that submits to the Secretary an applica-
tion under paragraph (1) shall submit to the Sec-
retary periodic reports describing the status of the
studies involved.
‘‘(3) EXTENSION OF TIME REGARDING PLANNED
STUDIES.—The period of 36 months authorized in
paragraph (1)(A)(ii) for the completion of studies
may be extended by the Secretary if the manufacturer
involved submits to the Secretary a written request
for the extension and the Secretary determines that
the manufacturer has acted with due diligence to con-
duct the studies in a timely manner. Such extension
may not provide more than 24 additional months.
‘‘(d) EXEMPTION FROM REQUIREMENT OF SUPPLE-
MENTAL APPLICATION.—
‘‘(1) IN GENERAL.—For purposes of subsection
(a)(2), a manufacturer may disseminate information
on a new use if—
‘‘(A) the manufacturer has submitted to the
Secretary an application for an exemption from
meeting the requirement of subsection (a)(1); and
‘‘(B)(i) the Secretary has approved the ap-
plication in accordance with paragraph (2); or
‘‘(ii) the application is deemed under para-
graph (3)(A) to have been approved (unless such
approval is terminated pursuant to paragraph
(3)(B)).
‘‘(2) CONDITIONS
FOR
APPROVAL.—The Sec-
retary may approve an application under paragraph
(1) for an exemption only if the Secretary determines
that—
‘‘(A) it would be economically prohibitive
with respect to such drug for the manufacturer
to incur the costs necessary for the submission of
a supplemental application for reasons, as de-
fined by the Secretary, such as the lack of avail-
ability under law of any period during which
the manufacturer would have exclusive market-
ing rights with respect to the new use involved
or that the population expected to benefit from
approval of the supplemental application is
small; or
‘‘(B) it would be unethical to conduct the
studies necessary for the supplemental applica-
tion for a reason such as the new use involved
is the standard of medical care for a health con-
dition.
‘‘(3) TIME FOR CONSIDERATION OF APPLICATION;
DEEMED APPROVAL.—
‘‘(A) IN GENERAL.—The Secretary shall ap-
prove or deny an application under paragraph
(1) for an exemption not later than 60 days after
the receipt of the application. If the Secretary
does not comply with the preceding sentence, the
application is deemed to be approved.
‘‘(B) 
TERMINATION
OF
DEEMED
AP-
PROVAL.—If pursuant to a deemed approval
under subparagraph (A) a manufacturer dis-
seminates written information under section 745
on a new use, the Secretary may at any time
terminate such approval and under section
749(b)(3) order the manufacturer to cease dis-
seminating the information.
‘‘(e) REQUIREMENTS REGARDING APPLICATIONS.—
Applications under this section shall be submitted in the
form and manner prescribed by the Secretary.
‘‘(f) TRANSITION RULE.—For purposes of this section,
in any case in which a manufacturer has submitted to the
Secretary a supplemental application for which action by
the Secretary is pending as of the date of the enactment
of the Prescription Drug User Fee Reauthorization and
Drug and Biological Products Regulatory Modernization
Act of 1997, the application is deemed to be a supplemental
application submitted under subsection (b).
‘‘SEC. 749. CORRECTIVE ACTIONS; CESSATION OF DISSEMI-
NATION.
‘‘(a) POSTDISSEMINATION DATA REGARDING SAFETY
AND EFFECTIVENESS.—
‘‘(1) CORRECTIVE
ACTIONS.—With respect to
data received by the Secretary after the dissemination
of information under section 745 by a manufacturer
has begun (whether received pursuant to paragraph
(2) or otherwise), if the Secretary determines that the
data indicate that the new use involved may not be
effective or may present a significant risk to public
health, the Secretary shall, in consultation with the
manufacturer, take such action regarding the dissemi-
nation of the information as the Secretary determines
to be appropriate for the protection of the public
health, which may include ordering that the manufac-
turer cease the dissemination of the information.
‘‘(2) RESPONSIBILITIES OF MANUFACTURERS TO
SUBMIT
DATA.—After a manufacturer disseminates
information pursuant to section 745, the manufac-
turer shall submit to the Secretary a notification of
any additional knowledge of the manufacturer on
clinical research or other data that relate to the safety
or effectiveness of the new use involved. If the manu-
facturer is in possession of the data, the notification
shall include the data. The Secretary shall by regula-
tion establish the scope of the responsibilities of man-
ufacturers under this paragraph, including such lim-
its on the responsibilities as the Secretary determines
to be appropriate.
‘‘(b) CESSATION OF DISSEMINATION.—
‘‘(1) FAILURE OF MANUFACTURER TO COMPLY
WITH REQUIREMENTS.—The Secretary may order a
manufacturer to cease the dissemination of informa-
tion pursuant to section 745 if the Secretary deter-
mines that the information being disseminated does
not comply with the requirements established in this
subchapter. Such an order may be issued only after
the Secretary has provided notice to the manufacturer
of the intent of the Secretary to issue the order and
has provided an opportunity for a meeting with re-
spect to such intent unless paragraph (2)(B) applies.
If the failure of the manufacturer constitutes a minor
violation of this subchapter, the Secretary shall delay
issuing the order and provide to the manufacturer an
opportunity to correct the violation.
‘‘(2) SUPPLEMENTAL
APPLICATIONS.—The Sec-
retary may order a manufacturer to cease the dis-
semination of information pursuant to section 745 if
the Secretary determines that—
‘‘(A) in the case of a manufacturer to which
section 748(b) applies, the Secretary determines
that the supplemental application received under
such section does not contain adequate informa-
tion for approval of the new use with respect to
which the application was submitted; or
‘‘(B) in the case of a manufacturer to which
section 748(c) applies, the Secretary determines,
after an informal hearing, that the manufacturer
is not acting with due diligence to complete the
studies involved.
‘‘(3) TERMINATION
OF
DEEMED
APPROVAL
OF
EXEMPTION
REGARDING
SUPPLEMENTAL
APPLICA-
TIONS.—If under section 748(d)(3) the Secretary ter-
minates a deemed approval of an exemption, the Sec-
retary may order the manufacturer involved to cease
disseminating the information. A manufacturer shall
comply with an order under the preceding sentence
not later than 60 days after the receipt of the order.
‘‘(c) CORRECTIVE ACTIONS BY MANUFACTURERS.—
‘‘(1) IN GENERAL.—In any case in which under
this section the Secretary orders a manufacturer to
cease disseminating information, the Secretary may
order the manufacturer to take action to correct the
information that has been disseminated, except as
provided in paragraph (2).
‘‘(2) TERMINATION
OF
DEEMED
APPROVAL
OF
EXEMPTION
REGARDING
SUPPLEMENTAL
APPLICA-
TIONS.—In the case of an order under subsection
(b)(3) to cease disseminating information, the Sec-
retary may not order the manufacturer involved to
take action to correct the information that has been
disseminated unless the Secretary determines that the
new use described in the information would pose a
significant risk to the public health.
‘‘SEC. 750. DEFINITIONS.
‘‘For purposes of this subchapter:
‘‘(1) The term ‘health care practitioner’ means a
physician, or other individual who is a provider of
health care, who is licensed under the law of a State
to prescribe drugs.
‘‘(2) The terms ‘health insurance issuer’ and
‘group health plan’ have the meaning given such
terms under section 2791 of the Public Health Service
Act.
‘‘(3) The term ‘manufacturer’ means a person
who manufactures a drug, or who is licensed by such
person to distribute or market the drug.
‘‘(4) The term ‘new use’, with respect to a drug,
means a use that is not included in the approved la-
beling of the drug.
‘‘(5) The term ‘pharmacy benefit manager’
means an organization that—
‘‘(A) 
manages 
pharmaceutical 
costs
through—
‘‘(i) pharmacy benefit administration,
including claims processing adjudication,
pharmacy networks, mail service, and data
reporting;
‘‘(ii) formulary management and con-
tracting, including evaluating drugs for for-
mulary status, negotiations of contracts
with manufacturers, and disbursement of
rebates; and
‘‘(iii) utilization management, includ-
ing communicating and enforcing therapy
guidelines and drug use principles to physi-
cians, pharmacists, and patients; and
‘‘(B) serves 2 principal types of customers
which are—
‘‘(i) employers, both private- and pub-
lic-sector, who use either self-funded health
benefits through a third party administra-
tor’s insurance carrier or use traditional
indemnity coverage, using providers from a
preferred provider network or in a fee-for-
service capacity; and
‘‘(ii) health maintenance organiza-
tions.
‘‘(6) The term ‘scientific or medical journal’
means a scientific or medical publication—
‘‘(A) that is published by an organization—
‘‘(i) that has an editorial board;
‘‘(ii) that utilizes experts, who have
demonstrated expertise in the subject of an
article under review by the organization
and who are independent of the organiza-
tion, to review and objectively select, reject,
or provide comments about proposed arti-
cles; and
‘‘(iii) that has a publicly stated policy,
to which the organization adheres, of full
disclosure of any conflict of interest or bi-
ases for all authors or contributors involved
with the journal or organization;
‘‘(B) whose articles are peer-reviewed and
published in accordance with the regular peer-re-
view procedures of the organization;
‘‘(C) that is generally recognized to be of
national scope and reputation;
‘‘(D) that is indexed in the Index Medicus
of the National Library of Medicine of the Na-
tional Institutes of Health; and
‘‘(E) that is not in the form of a special
supplement that has been funded in whole or in
part by 1 or more manufacturers.
‘‘SEC. 751. RULES OF CONSTRUCTION.
‘‘(a) UNSOLICITED REQUEST.—Nothing in section 745
shall be construed as prohibiting a manufacturer from dis-
seminating information in response to an unsolicited re-
quest from a health care practitioner.
‘‘(b) DISSEMINATION OF INFORMATION ON DRUGS NOT
EVIDENCE
OF
INTENDED
USE.—Notwithstanding sub-
section (a), (f), or (o) of section 502, or any other provision
of law, the dissemination of information relating to a new
use of a drug, in accordance with section 745, shall not
be construed by the Secretary as evidence of a new intended
use of the drug that is different from the intended use of
the drug set forth in the official labeling of the drug. Such
dissemination shall not be considered by the Secretary as
labeling, adulteration, or misbranding of the drug.
‘‘(c) PATENT PROTECTION.—Nothing in section 745
shall affect patent rights in any manner.
‘‘(d) AUTHORIZATION FOR DISSEMINATION OF ARTI-
CLES AND FEES FOR REPRINTS OF ARTICLES.—Nothing in
section 745 shall be construed as prohibiting an entity that
publishes a scientific journal (as defined in section 750(6))
from requiring authorization from the entity to disseminate
an article published by such entity or charging fees for the
purchase of reprints of published articles from such entity.’’.
(b) PROHIBITED ACT.—Section 301 (21 U.S.C. 331)
is amended by adding at the end the following:
‘‘(x) The dissemination of information in violation of
section 745.’’.
(c) REGULATIONS.—Not later than 1 year after the
date of enactment of this Act, the Secretary of Health and
Human Services shall promulgate regulations to implement
the amendments made by this section.
(d) EFFECTIVE DATE.—The amendments made by this
section shall take effect 1 year after the date of enactment
of this Act, or upon the Secretary’s issuance of final regula-
tions pursuant to subsection (c), whichever is sooner.
(e) SUNSET.—The amendments made by this section
cease to be effective September 30, 2006, or 7 years after
the date on which the Secretary promulgates the regulations
described in subsection (c), whichever is later.
SEC. 8. STUDIES AND REPORTS.
(a) IN GENERAL.—The Comptroller General of the
United States shall conduct a study—
(1) to determine the impact of the amendments
made by section 7 on the resources of the Department
of Health and Human Services; and
(2) of the scientific issues raised as a result of
the amendments made by section 7, including issues
relating to—
(A) the effectiveness of such amendments
with respect to the provision of useful scientific
information to health care practitioners;
(B) the quality of the information being dis-
seminated pursuant to such amendments;
(C) the quality and usefulness of the infor-
mation provided, in accordance with such
amendments, by the Secretary or by a manufac-
turer at the request of the Secretary; and
(D) the impact of such amendments on re-
search in the area of new uses of drugs, indica-
tions for new uses, or dosages of drugs for new
uses, particularly the impact on pediatric indi-
cations and rare diseases.
(b) REPORT.—Not later than January 1, 2002, the
Comptroller General of the United States shall prepare and
submit to the Committee on Labor and Human Resources
of the Senate and the Committee on Commerce of the House
of Representatives a report of the results of the study under
subsection (a).
SEC. 9. APPROVAL OF SUPPLEMENTAL APPLICATIONS FOR
APPROVED PRODUCTS.
(a) PERFORMANCE STANDARDS.—Not later than 180
days after the date of enactment of this Act, the Secretary
shall publish in the Federal Register performance standards
for the prompt review of supplemental applications submit-
ted for approved drugs under the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321 et seq.) or section 351 of the
Public Health Service Act (42 U.S.C. 262).
(b) GUIDANCE TO INDUSTRY.—Not later than 180 days
after the date of enactment of this Act, the Secretary shall
issue final guidances to clarify the requirements for, and
facilitate the submission of data to support, the approval
of supplemental applications for the approved articles de-
scribed in subsection (a). The guidances shall—
(1) clarify circumstances in which published
matter may be the basis for approval of a supple-
mental application;
(2) specify data requirements that will avoid du-
plication of previously submitted data by recognizing
the availability of data previously submitted in sup-
port of an original application; and
(3) define supplemental applications that are eli-
gible for priority review.
(c) RESPONSIBILITIES OF CENTERS.—The Secretary
shall designate an individual in each center within the
Food and Drug Administration which is responsible for the
review of applications for approval of drugs for—
(1) encouraging the prompt review of supple-
mental applications for approved articles; and
(2) working with sponsors to facilitate the devel-
opment and submission of data to support supple-
mental applications.
(d) COLLABORATION.—The Secretary shall implement
programs and policies that will foster collaboration between
the Food and Drug Administration, the National Institutes
of Health, professional medical and scientific societies, and
other persons, to identify published and unpublished studies
that may support a supplemental application, and to en-
courage sponsors to make supplemental applications or con-
duct further research in support of a supplemental applica-
tion based, in whole or in part, on such studies.
SEC. 10. HEALTH CARE ECONOMIC INFORMATION.
Section 502(a) (21 U.S.C. 352(a)) is amended by add-
ing at the end the following: ‘‘Health care economic infor-
mation provided to a formulary committee, or other similar
entity, in the course of the committee or the entity carrying
out its responsibilities for the selection of drugs for managed
care or other similar organizations, shall not be considered
to be false or misleading if the health care economic infor-
mation directly relates to an indication approved under
section 505 or 507 or section 351(a) of the Public Health
Service Act (42 U.S.C. 262(a)) for such drug and is based
on competent and reliable scientific evidence. The require-
ments set forth in section 505(a), 507, or section 351(a) of
the Public Health Service Act (42 U.S.C. 262(a)) shall not
apply to health care economic information provided to such
a committee or entity in accordance with this paragraph.
Information that is relevant to the substantiation of the
health care economic information presented pursuant to
this paragraph shall be made available to the Secretary
upon request. In this paragraph, the term ‘health care eco-
nomic information’ means any analysis that identifies,
measures, or compares the economic consequences, including
the costs of the represented health outcomes, of the use of
a drug to the use of another drug, to another health care
intervention, or to no intervention.’’.
SEC. 11. CLINICAL INVESTIGATIONS.
(a) CLARIFICATION OF THE NUMBER OF REQUIRED
CLINICAL
INVESTIGATIONS
FOR
APPROVAL.—Section
505(d) (21 U.S.C. 355(d)) is amended by adding at the end
the following: ‘‘If the Secretary determines, based on rel-
evant science, that data from one adequate and well-con-
trolled clinical investigation and confirmatory evidence (ob-
tained prior to or after such investigation) are sufficient
to establish effectiveness, the Secretary may consider such
data and evidence to constitute substantial evidence for pur-
poses of the preceding sentence.’’.
(b) WOMEN AND MINORITIES.—Section 505(b)(1) (21
U.S.C. 355(b)(1)) is amended by adding at the end the fol-
lowing: ‘‘The Secretary shall, in consultation with the Di-
rector of the National Institutes of Health, review and de-
velop guidance, as appropriate, on the inclusion of women
and minorities in clinical trials required by clause (A).’’.
SEC. 12. MANUFACTURING CHANGES FOR DRUGS.
(a) IN GENERAL.—Chapter VII (21 U.S.C. 371 et
seq.), as amended by section 7, is amended by adding at
the end the following subchapter:
‘‘SUBCHAPTER F—MANUFACTURING CHANGES
‘‘SEC. 755. MANUFACTURING CHANGES.
‘‘(a) IN GENERAL.—With respect to a drug for which
there is in effect an approved application under section 505
or 512 or a license under section 351 of the Public Health
Service Act, a change from the manufacturing process ap-
proved pursuant to such application or license may be
made, and the drug as made with the change may be dis-
tributed, if—
‘‘(1) the holder of the approved application or li-
cense (referred to in this section as a ‘holder’) has
validated the effects of the change in accordance with
subsection (b); and
‘‘(2)(A) in the case of a major manufacturing
change, the holder has complied with the requirements
of subsection (c); or
‘‘(B) in the case of a change that is not a major
manufacturing change, the holder complies with the
applicable requirements of subsection (d).
‘‘(b) VALIDATION
OF EFFECTS
OF CHANGES.—For
purposes of subsection (a)(1), a drug made with a manufac-
turing change (whether a major manufacturing change or
otherwise) may be distributed only if, before distribution
of the drug as so made, the holder involved validates the
effects of the change on the identity, strength, quality, pu-
rity, and potency of the drug as the identity, strength, qual-
ity, purity, and potency may relate to the safety, bioequiva-
lence, bioavailability, or effectiveness of the drug.
‘‘(c) MAJOR MANUFACTURING CHANGES.—
‘‘(1) REQUIREMENT OF SUPPLEMENTAL APPLICA-
TION.—For purposes of subsection (a)(2)(A), a drug
made with a major manufacturing change may be
distributed only if, before the distribution of the drug
as so made, the holder involved submits to the Sec-
retary a supplemental application for such change
and the Secretary approves the application. The ap-
plication shall contain such information as the Sec-
retary determines to be appropriate, and shall include
the information developed under subsection (b) by the
holder in validating the effects of the change.
‘‘(2) 
CHANGES
QUALIFYING
AS
MAJOR
CHANGES.—For purposes of subsection (a)(2)(A), a
major manufacturing change is a manufacturing
change that—
‘‘(A) is determined by the Secretary to have
substantial potential to adversely affect the iden-
tity, strength, quality, purity, or potency of the
drug as they may relate to the safety, bioequiva-
lence, bioavailability, or effectiveness of a drug;
and
‘‘(B)(i) is made in the qualitative or quan-
titative formulation of the drug involved or in
the specifications in the approved application or
license referred to in subsection (a) for the drug
(unless exempted by the Secretary from the re-
quirements of this subsection);
‘‘(ii) is determined by the Secretary by reg-
ulation or guidance to require completion of an
appropriate clinical study demonstrating equiva-
lence of the drug to the drug as manufactured
without the change; or
‘‘(iii) is determined by the Secretary by reg-
ulation or guidance to have a substantial poten-
tial to adversely affect the safety or effectiveness
of the drug.
‘‘(d) OTHER MANUFACTURING CHANGES.—
‘‘(1) IN GENERAL.—For purposes of subsection
(a)(2)(B), the Secretary may regulate drugs made
with manufacturing changes that are not major man-
ufacturing changes as follows:
‘‘(A) The Secretary may authorize holders
to distribute such drugs without prior approval
by the Secretary.
‘‘(B) The Secretary may require that, prior
to the distribution of such drugs, holders submit
to the Secretary supplemental applications for
such changes.
‘‘(C) The Secretary may establish categories
of such changes and designate categories to which
subparagraph (A) applies and categories to
which subparagraph (B) applies.
‘‘(2) CHANGES NOT REQUIRING SUPPLEMENTAL
APPLICATION.—
‘‘(A) SUBMISSION
OF
REPORT.—A holder
making a manufacturing change to which para-
graph (1)(A) applies shall submit to the Sec-
retary a report on the change, which shall con-
tain such information as the Secretary deter-
mines to be appropriate, and which shall include
the information developed under subsection (b)
by the holder in validating the effects of the
change. The report shall be submitted by such
date as the Secretary may specify.
‘‘(B) AUTHORITY REGARDING ANNUAL RE-
PORTS.—In the case of a holder that during a
single year makes more than one manufacturing
change to which paragraph (1)(A) applies, the
Secretary may in carrying out subparagraph
(A) authorize the holder to comply with such
subparagraph by submitting a single report for
the year that provides the information required
in such subparagraph for all the changes made
by the holder during the year.
‘‘(3) CHANGES REQUIRING SUPPLEMENTAL AP-
PLICATION.—
‘‘(A) SUBMISSION
OF
SUPPLEMENTAL
AP-
PLICATION.—The supplemental application re-
quired under paragraph (1)(B) for a manufac-
turing change shall contain such information as
the Secretary determines to be appropriate,
which shall include the information developed
under subsection (b) by the holder in validating
the effects of the change.
‘‘(B) AUTHORITY
FOR
DISTRIBUTION.—In
the case of a manufacturing change to which
paragraph (1)(B) applies:
‘‘(i) The holder involved may com-
mence distribution of the drug involved 30
days after the Secretary receives the supple-
mental application under such paragraph,
unless the Secretary notifies the holder with-
in such 30-day period that prior approval
of the application is required before dis-
tribution may be commenced.
‘‘(ii) The Secretary may designate a
category of such changes for the purpose of
providing that, in the case of a change that
is in such category, the holder involved may
commence distribution of the drug involved
upon the receipt by the Secretary of a sup-
plemental application for the change.
‘‘(iii) If the Secretary disapproves the
supplemental application, the Secretary
may order the manufacturer to cease the
distribution of the drugs that have been
made with the manufacturing change.’’.
(b) TRANSITION RULE.—The amendment made by sub-
section (a) takes effect upon the effective date of regulations
promulgated by the Secretary of Health and Human Serv-
ices to implement such amendment, or upon the expiration
of the 24-month period beginning on the date of the enact-
ment of this Act, whichever occurs first.
SEC. 13. STREAMLINING CLINICAL RESEARCH ON DRUGS.
Section 505(i) (21 U.S.C. 355(i)) is amended by add-
ing ‘‘(1)’’ before ‘‘The Secretary’’, by redesignating para-
graphs (1), (2), and (3) as subparagraphs (A), (B), and
(C), respectively, by striking the last two sentences, and by
adding the following new paragraphs:
‘‘(2) Subject to paragraph (3), a clinical investigation
of a new drug may begin 30 days after the Secretary has
received from the manufacturer or sponsor of the investiga-
tion a submission containing such information about the
drug and the clinical investigation, including—
‘‘(A) information on design of the investigation
and adequate reports of basic information, certified
by the applicant to be accurate reports, necessary to
assess the safety of the drug for use in clinical inves-
tigation; and
‘‘(B) adequate information on the chemistry and
manufacturing of the drug, controls available for the
drug, and primary data tabulations from animal or
human studies.
‘‘(3)(A) At any time, the Secretary may prohibit the
sponsor of an investigation from conducting the investiga-
tion (referred to in this paragraph as a ‘clinical hold’) if
the Secretary makes a determination described in subpara-
graph (B). The Secretary shall specify the basis for the clin-
ical hold, including the specific information available to the
Secretary which served as the basis for such clinical hold,
and confirm such determination in writing.
‘‘(B) For purposes of subparagraph (A), a determina-
tion described in this subparagraph with respect to a clini-
cal hold is that—
‘‘(i) the drug involved represents an unreason-
able risk to the safety of the persons who are the sub-
ject of the clinical investigation, taking into account
the qualifications of the clinical investigators, infor-
mation about the drug, the design of the clinical in-
vestigation, the condition for which the drug is to be
investigated, and the health status of the subjects in-
volved; or
‘‘(ii) the clinical hold should be issued for such
other reasons as the Secretary may by regulation es-
tablish (including reasons established by regulation
before the date of the enactment of the Prescription
Drug User Fee Reauthorization and Drug Regulatory
Modernization Act of 1997).
Such regulations shall provide that such exemption shall
be conditioned upon the manufacturer, or the sponsor of the
investigation, requiring that experts using such drugs for
investigational purposes certify to such manufacturer or
sponsor that they will inform any human beings to whom
such drugs, or any controls used in connection therewith,
are being administered, or their representatives, that such
drugs are being used for investigational purposes and will
obtain the consent of such human beings or their representa-
tives, except where they deem it not feasible or, in their pro-
fessional judgment, contrary to the best interests of such
human beings. Nothing in this subsection shall be construed
to require any clinical investigator to submit directly to
the Secretary reports on the investigational use of drugs.
‘‘(C) Any request to the Secretary from the sponsor of
an investigation that a clinical hold be removed shall re-
ceive a decision, in writing and specifying the reasons
therefor, within 30 days after receipt of such request. Any
such request shall include sufficient information to support
the removal of such clinical hold.’’.
SEC. 14. DATA REQUIREMENTS FOR DRUGS.
Within 12 months after the date of enactment of this
Act, the Secretary of the Health and Human Services, act-
ing through the Commissioner of Food and Drugs, shall
issue guidance that describes, for certain types of studies,
when abbreviated study reports may be submitted, in lieu
of full reports, with a new drug application under section
505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
355) and with a biologics license application under section
351 of the Public Health Service Act (42 U.S.C. 262). Such
guidance shall describe the kinds of studies for which abbre-
viated reports are appropriate and the appropriate abbre-
viated report formats.
SEC. 15. CONTENT AND REVIEW OF APPLICATIONS.
(a) SECTION
505(b).—Section 505(b) (21 U.S.C.
355(b)) is amended by adding at the end the following:
‘‘(4)(A) The Secretary shall issue guidance for the re-
view of applications submitted under paragraph (1) relat-
ing to promptness, technical excellence, lack of bias and con-
flict of interest, and knowledge of regulatory and scientific
standards which shall apply equally to all individuals who
review such applications.
‘‘(B) The Secretary shall meet with a sponsor of an
investigation or an applicant for approval under this sec-
tion or section 351 of the Public Health Service Act if the
sponsor or applicant makes a reasonable request for a meet-
ing, for the purpose of reaching agreement on the design
and size of clinical trials. Minutes of any such meeting shall
be prepared by the Secretary and made available to the
sponsor or applicant upon request.
‘‘(C) Agreement regarding the parameters of the design
and size of clinical trials of a new drug that are reached
between the Secretary and a sponsor or applicant shall be
reduced to writing and made part of the administrative
record by the Secretary. Such agreement shall not be
changed after the testing begins, except—
‘‘(i) with the written agreement of the sponsor or
applicant; or
‘‘(ii) pursuant to a decision, made in accordance
with subparagraph (D) by the director of the division
in which the drug is reviewed, that a substantial sci-
entific issue essential to determining the safety or ef-
fectiveness of the drug has been identified after the
testing has begun.
‘‘(D) A decision under subparagraph (C)(ii) by the di-
rector shall be in writing and the Secretary shall provide
to the sponsor or applicant an opportunity for a meeting
at which the director and the sponsor or applicant will be
present and at which the director documents the scientific
issue involved.
‘‘(E) The written decisions of the reviewing division
shall be binding upon, and may not directly or indirectly
be changed by, the field or compliance division personnel
unless such field or compliance division personnel dem-
onstrate to the reviewing division why such decision should
be modified. For purposes of this paragraph, the reviewing
division is the division responsible for the review of an ap-
plication for approval of a drug (including all scientific
and medical matters, chemistry, manufacturing, and con-
trols).
‘‘(F) No action by the reviewing division may be de-
layed because of the unavailability of information from or
action by field personnel unless the reviewing division de-
termines that a delay is necessary to assure the marketing
of a safe and effective drug.’’.
(b) SECTION 505(j).—
(1) AMENDMENT.—Section 505(j) (21 U.S.C
355(j)) is amended by redesignating paragraphs (3)
through (8) as paragraphs (4) through (9), respec-
tively, and by adding after paragraph (2) the follow-
ing:
‘‘(3)(A) The Secretary shall issue guidance for the re-
view of applications submitted under paragraph (1) relat-
ing to promptness, technical excellence, lack of bias and con-
flict of interest, and knowledge of regulatory and scientific
standards which shall apply equally to all individuals who
review such applications.
‘‘(B) The Secretary shall meet with an applicant for
approval of a drug under this subsection if the applicant
makes a reasonable request for a meeting for the purpose
of reaching agreement on the design and size of studies
needed for approval of such application. Minutes of any
such meeting shall be prepared by the Secretary and made
available to the sponsor or applicant.
‘‘(C) Agreements regarding the parameters of design
and size of bioavailability and bioequivalence trials of a
drug under this subsection that are reached between the Sec-
retary and a sponsor or applicant shall be reduced to writ-
ing and made part of the administrative record by the Sec-
retary. Such agreement shall not be changed after the test-
ing begins, except—
‘‘(i) with the written agreement of the sponsor or
applicant; or
‘‘(ii) pursuant to a decision, made in accordance
with subparagraph (D) by the director of the division
in which the drug is reviewed, that a substantial sci-
entific issue essential to determining the safety or ef-
fectiveness of the drug has been identified after the
testing has begun.
‘‘(D) A decision under subparagraph (C)(ii) by the di-
rector shall be in writing and the Secretary shall provide
to the sponsor or applicant an opportunity for a meeting
at which the director and the sponsor or applicant will be
present and at which the director documents the scientific
issue involved.
‘‘(E) The written decisions of the reviewing division
shall be binding upon, and may not directly or indirectly
be changed by, the field or compliance office personnel un-
less such field or compliance office personnel demonstrate
to the reviewing division why such decision should be modi-
fied. For purposes of this paragraph, the reviewing division
is the division responsible for the review of an application
under this subsection (including scientific matters, chem-
istry, manufacturing, and controls).
‘‘(F) No action by the reviewing division may at any
time be delayed because of the unavailability of information
from or action by field personnel unless the reviewing divi-
sion determines that a delay is necessary to assure the mar-
keting of a safe and effective drug.’’.
(2) CONFORMING AMENDMENTS.—Section 505(j)
(21 U.S.C. 355(j)), as amended by paragraph (1), is
amended—
(A) in paragraph (2)(A)(i), by striking
‘‘(6)’’ and inserting ‘‘(7)’’;
(B) in paragraph (4), by striking ‘‘(4)’’ and
inserting ‘‘(5)’’;
(C) in paragraph (4)(I), by striking ‘‘(5)’’
and inserting ‘‘(6)’’; and
(D) in paragraph (7)(C), by striking ‘‘(5)’’
each place it occurs and inserting ‘‘(6)’’.
SEC. 16. SCIENTIFIC ADVISORY PANELS.
Section 505 (21 U.S.C. 355) is amended by adding
at the end the following:
‘‘(n)(1) For the purpose of providing expert scientific
advice and recommendations to the Secretary regarding a
clinical investigation of a drug or the approval for market-
ing of a drug under section 505 or section 351 of the Public
Health Service Act, the Secretary shall establish panels of
experts or use panels of experts established before the date
of the enactment of this subsection, or both.
‘‘(2) The Secretary may delegate the appointment and
oversight authority granted under section 904 to a director
of a center or successor entity within the Food and Drug
Administration.
‘‘(3) The Secretary shall make appointments to each
panel established under paragraph (1) so that each panel
shall consist of—
‘‘(A) members who are qualified by training and
experience to evaluate the safety and effectiveness of
119
The Secretary shall compile the list required by paragraph
(1) within 2 years after the date of the enactment of this
section and shall provide the analysis required by para-
graph (2) within 2 years of such date of enactment.
(b) STUDY.—The Secretary of Health and Human
Services, acting through the Food and Drug Administra-
tion, shall conduct a study of the effect on humans of the
use of mercury compounds in nasal sprays. Such study
shall include data from other studies that have been made
of such use.
(c) STUDY OF MERCURY SALES.—
(1) STUDY.—The Secretary of Health and
Human Services, acting through the Food and Drug
Administration and subject to appropriations, shall
conduct, or shall contract with the Institute of Medi-
cine of the National Academy of Sciences to conduct,
a study of the effect on humans of the use of ele-
mental, organic or inorganic mercury when offered
for sale as a drug or dietary supplement. Such study
shall, among other things, evaluate—
(A) the scope of mercury use as a drug or
dietary supplement; and
(B) the adverse effects on health of children
and other sensitive populations resulting from