
From the U.S. Code Online via GPO Access
[wais.access.gpo.gov]
[Laws in effect as of January 2, 2001]
[Document affected by Public Law 107-109 Section 15(c)(1)]
[Document affected by Public Law 107-109 Section 15(d)]
[CITE: 21USC355]

 
                        TITLE 21--FOOD AND DRUGS
 
             CHAPTER 9--FEDERAL FOOD, DRUG, AND COSMETIC ACT
 
                     SUBCHAPTER V--DRUGS AND DEVICES
 
                        Part A--Drugs and Devices
 
Sec. 355. New drugs


(a) Necessity of effective approval of application

    No person shall introduce or deliver for introduction into 
interstate commerce any new drug, unless an approval of an application 
filed pursuant to subsection (b) or (j) of this section is effective 
with respect to such drug.

(b) Filing application; contents

    (1) Any person may file with the Secretary an application with 
respect to any drug subject to the provisions of subsection (a) of this 
section. Such person shall submit to the Secretary as a part of the 
application (A) full reports of investigations which have been made to 
show whether or not such drug is safe for use and whether such drug is 
effective in use; (B) a full list of the articles used as components of 
such drug; (C) a full statement of the composition of such drug; (D) a 
full description of the methods used in, and the facilities and controls 
used for, the manufacture, processing, and packing of such drug; (E) 
such samples of such drug and of the articles used as components thereof 
as the Secretary may require; and (F) specimens of the labeling proposed 
to be used for such drug. The applicant shall file with the application 
the patent number and the expiration date of any patent which claims the 
drug for which the applicant submitted the application or which claims a 
method of using such drug and with respect to which a claim of patent 
infringement could reasonably be asserted if a person not licensed by 
the owner engaged in the manufacture, use, or sale of the drug. If an 
application is filed under this subsection for a drug and a patent which 
claims such drug or a method of using such drug is issued after the 
filing date but before approval of the application, the applicant shall 
amend the application to include the information required by the 
preceding sentence. Upon approval of the application, the Secretary 
shall publish information submitted under the two preceding sentences. 
The Secretary shall, in consultation with the Director of the National 
Institutes of Health and with representatives of the drug manufacturing 
industry, review and develop guidance, as appropriate, on the inclusion 
of women and minorities in clinical trials required by clause (A).
    (2) An application submitted under paragraph (1) for a drug for 
which the investigations described in clause (A) of such paragraph and 
relied upon by the applicant for approval of the application were not 
conducted by or for the applicant and for which the applicant has not 
obtained a right of reference or use from the person by or for whom the 
investigations were conducted shall also include--
        (A) a certification, in the opinion of the applicant and to the 
    best of his knowledge, with respect to each patent which claims the 
    drug for which such investigations were conducted or which claims a 
    use for such drug for which the applicant is seeking approval under 
    this subsection and for which information is required to be filed 
    under paragraph (1) or subsection (c) of this section--
            (i) that such patent information has not been filed,
            (ii) that such patent has expired,
            (iii) of the date on which such patent will expire, or
            (iv) that such patent is invalid or will not be infringed by 
        the manufacture, use, or sale of the new drug for which the 
        application is submitted; and

        (B) if with respect to the drug for which investigations 
    described in paragraph (1)(A) were conducted information was filed 
    under paragraph (1) or subsection (c) of this section for a method 
    of use patent which does not claim a use for which the applicant is 
    seeking approval under this subsection, a statement that the method 
    of use patent does not claim such a use.

    (3)(A) An applicant who makes a certification described in paragraph 
(2)(A)(iv) shall include in the application a statement that the 
applicant will give the notice required by subparagraph (B) to--
        (i) each owner of the patent which is the subject of the 
    certification or the representative of such owner designated to 
    receive such notice, and
        (ii) the holder of the approved application under subsection (b) 
    of this section for the drug which is claimed by the patent or a use 
    of which is claimed by the patent or the representative of such 
    holder designated to receive such notice.

    (B) The notice referred to in subparagraph (A) shall state that an 
application has been submitted under this subsection for the drug with 
respect to which the certification is made to obtain approval to engage 
in the commercial manufacture, use, or sale of the drug before the 
expiration of the patent referred to in the certification. Such notice 
shall include a detailed statement of the factual and legal basis of the 
applicant's opinion that the patent is not valid or will not be 
infringed.
    (C) If an application is amended to include a certification 
described in paragraph (2)(A)(iv), the notice required by subparagraph 
(B) shall be given when the amended application is submitted.
    (4)(A) The Secretary shall issue guidance for the individuals who 
review applications submitted under paragraph (1) or under section 262 
of title 42, which shall relate to promptness in conducting the review, 
technical excellence, lack of bias and conflict of interest, and 
knowledge of regulatory and scientific standards, and 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 for a drug under this subsection or section 
262 of title 42 if the sponsor or applicant makes a reasonable written 
request for a meeting for the purpose of reaching agreement on the 
design and size of clinical trials intended to form the primary basis of 
an effectiveness claim. The sponsor or applicant shall provide 
information necessary for discussion and agreement on the design and 
size of the clinical trials. Minutes of any such meeting shall be 
prepared by the Secretary and made available to the sponsor or applicant 
upon request.
    (C) Any agreement regarding the parameters of the design and size of 
clinical trials of a new drug under this paragraph that is 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 reviewing division, that a 
    substantial scientific issue essential to determining the safety or 
    effectiveness of the drug has been identified after the testing has 
    begun.

    (D) A decision under subparagraph (C)(ii) by the director 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 will document 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 demonstrate to the reviewing division why such decision should 
be modified.
    (F) No action by the reviewing division may be delayed because of 
the unavailability of information from or action by field personnel 
unless the reviewing division determines that a delay is necessary to 
assure the marketing of a safe and effective drug.
    (G) For purposes of this paragraph, the reviewing division is the 
division responsible for the review of an application for approval of a 
drug under this subsection or section 262 of title 42 (including all 
scientific and medical matters, chemistry, manufacturing, and controls).

(c) Period for approval of application; period for, notice, and 
        expedition of hearing; period for issuance of order

    (1) Within one hundred and eighty days after the filing of an 
application under subsection (b) of this section, or such additional 
period as may be agreed upon by the Secretary and the applicant, the 
Secretary shall either--
        (A) approve the application if he then finds that none of the 
    grounds for denying approval specified in subsection (d) of this 
    section applies, or
        (B) give the applicant notice of an opportunity for a hearing 
    before the Secretary under subsection (d) of this section on the 
    question whether such application is approvable. If the applicant 
    elects to accept the opportunity for hearing by written request 
    within thirty days after such notice, such hearing shall commence 
    not more than ninety days after the expiration of such thirty days 
    unless the Secretary and the applicant otherwise agree. Any such 
    hearing shall thereafter be conducted on an expedited basis and the 
    Secretary's order thereon shall be issued within ninety days after 
    the date fixed by the Secretary for filing final briefs.

    (2) If the patent information described in subsection (b) of this 
section could not be filed with the submission of an application under 
subsection (b) of this section because the application was filed before 
the patent information was required under subsection (b) of this section 
or a patent was issued after the application was approved under such 
subsection, the holder of an approved application shall file with the 
Secretary the patent number and the expiration date of any patent which 
claims the drug for which the application was submitted or which claims 
a method of using such drug and with respect to which a claim of patent 
infringement could reasonably be asserted if a person not licensed by 
the owner engaged in the manufacture, use, or sale of the drug. If the 
holder of an approved application could not file patent information 
under subsection (b) of this section because it was not required at the 
time the application was approved, the holder shall file such 
information under this subsection not later than thirty days after 
September 24, 1984, and if the holder of an approved application could 
not file patent information under subsection (b) of this section because 
no patent had been issued when an application was filed or approved, the 
holder shall file such information under this subsection not later than 
thirty days after the date the patent involved is issued. Upon the 
submission of patent information under this subsection, the Secretary 
shall publish it.
    (3) The approval of an application filed under subsection (b) of 
this section which contains a certification required by paragraph (2) of 
such subsection shall be made effective on the last applicable date 
determined under the following:
        (A) If the applicant only made a certification described in 
    clause (i) or (ii) of subsection (b)(2)(A) of this section or in 
    both such clauses, the approval may be made effective immediately.
        (B) If the applicant made a certification described in clause 
    (iii) of subsection (b)(2)(A) of this section, the approval may be 
    made effective on the date certified under clause (iii).
        (C) If the applicant made a certification described in clause 
    (iv) of subsection (b)(2)(A) of this section, the approval shall be 
    made effective immediately unless an action is brought for 
    infringement of a patent which is the subject of the certification 
    before the expiration of forty-five days from the date the notice 
    provided under paragraph (3)(B) is received. If such an action is 
    brought before the expiration of such days, the approval may be made 
    effective upon the expiration of the thirty-month period beginning 
    on the date of the receipt of the notice provided under paragraph 
    (3)(B) or such shorter or longer period as the court may order 
    because either party to the action failed to reasonably cooperate in 
    expediting the action, except that--
            (i) if before the expiration of such period the court 
        decides that such patent is invalid or not infringed, the 
        approval may be made effective on the date of the court 
        decision,
            (ii) if before the expiration of such period the court 
        decides that such patent has been infringed, the approval may be 
        made effective on such date as the court orders under section 
        271(e)(4)(A) of title 35, or
            (iii) if before the expiration of such period the court 
        grants a preliminary injunction prohibiting the applicant from 
        engaging in the commercial manufacture or sale of the drug until 
        the court decides the issues of patent validity and infringement 
        and if the court decides that such patent is invalid or not 
        infringed, the approval shall be made effective on the date of 
        such court decision.

    In such an action, each of the parties shall reasonably cooperate in 
    expediting the action. Until the expiration of forty-five days from 
    the date the notice made under paragraph (3)(B) is received, no 
    action may be brought under section 2201 of title 28 for a 
    declaratory judgment with respect to the patent. Any action brought 
    under such section 2201 shall be brought in the judicial district 
    where the defendant has its principal place of business or a regular 
    and established place of business.
        (D)(i) If an application (other than an abbreviated new drug 
    application) submitted under subsection (b) of this section for a 
    drug, no active ingredient (including any ester or salt of the 
    active ingredient) of which has been approved in any other 
    application under subsection (b) of this section, was approved 
    during the period beginning January 1, 1982, and ending on September 
    24, 1984, the Secretary may not make the approval of another 
    application for a drug for which the investigations described in 
    clause (A) of subsection (b)(1) of this section and relied upon by 
    the applicant for approval of the application were not conducted by 
    or for the applicant and for which the applicant has not obtained a 
    right of reference or use from the person by or for whom the 
    investigations were conducted effective before the expiration of ten 
    years from the date of the approval of the application previously 
    approved under subsection (b) of this section.
        (ii) If an application submitted under subsection (b) of this 
    section for a drug, no active ingredient (including any ester or 
    salt of the active ingredient) of which has been approved in any 
    other application under subsection (b) of this section, is approved 
    after September 24, 1984, no application which refers to the drug 
    for which the subsection (b) application was submitted and for which 
    the investigations described in clause (A) of subsection (b)(1) of 
    this section and relied upon by the applicant for approval of the 
    application were not conducted by or for the applicant and for which 
    the applicant has not obtained a right of reference or use from the 
    person by or for whom the investigations were conducted may be 
    submitted under subsection (b) of this section before the expiration 
    of five years from the date of the approval of the application under 
    subsection (b) of this section, except that such an application may 
    be submitted under subsection (b) of this section after the 
    expiration of four years from the date of the approval of the 
    subsection (b) application if it contains a certification of patent 
    invalidity or noninfringement described in clause (iv) of subsection 
    (b)(2)(A) of this section. The approval of such an application shall 
    be made effective in accordance with this paragraph except that, if 
    an action for patent infringement is commenced during the one-year 
    period beginning forty-eight months after the date of the approval 
    of the subsection (b) application, the thirty-month period referred 
    to in subparagraph (C) shall be extended by such amount of time (if 
    any) which is required for seven and one-half years to have elapsed 
    from the date of approval of the subsection (b) application.
        (iii) If an application submitted under subsection (b) of this 
    section for a drug, which includes an active ingredient (including 
    any ester or salt of the active ingredient) that has been approved 
    in another application approved under subsection (b) of this 
    section, is approved after September 24, 1984, and if such 
    application contains reports of new clinical investigations (other 
    than bioavailability studies) essential to the approval of the 
    application and conducted or sponsored by the applicant, the 
    Secretary may not make the approval of an application submitted 
    under subsection (b) of this section for the conditions of approval 
    of such drug in the approved subsection (b) application effective 
    before the expiration of three years from the date of the approval 
    of the application under subsection (b) of this section if the 
    investigations described in clause (A) of subsection (b)(1) of this 
    section and relied upon by the applicant for approval of the 
    application were not conducted by or for the applicant and if the 
    applicant has not obtained a right of reference or use from the 
    person by or for whom the investigations were conducted.
        (iv) If a supplement to an application approved under subsection 
    (b) of this section is approved after September 24, 1984, and the 
    supplement contains reports of new clinical investigations (other 
    than bioavailabilty \1\ studies) essential to the approval of the 
    supplement and conducted or sponsored by the person submitting the 
    supplement, the Secretary may not make the approval of an 
    application submitted under subsection (b) of this section for a 
    change approved in the supplement effective before the expiration of 
    three years from the date of the approval of the supplement under 
    subsection (b) of this section if the investigations described in 
    clause (A) of subsection (b)(1) of this section and relied upon by 
    the applicant for approval of the application were not conducted by 
    or for the applicant and if the applicant has not obtained a right 
    of reference or use from the person by or for whom the 
    investigations were conducted.
---------------------------------------------------------------------------
    \1\ So in original. Probably should be ``bioavailability''.
---------------------------------------------------------------------------
        (v) If an application (or supplement to an application) 
    submitted under subsection (b) of this section for a drug, which 
    includes an active ingredient (including any ester or salt of the 
    active ingredient) that has been approved in another application 
    under subsection (b) of this section, was approved during the period 
    beginning January 1, 1982, and ending on September 24, 1984, the 
    Secretary may not make the approval of an application submitted 
    under this subsection and for which the investigations described in 
    clause (A) of subsection (b)(1) of this section and relied upon by 
    the applicant for approval of the application were not conducted by 
    or for the applicant and for which the applicant has not obtained a 
    right of reference or use from the person by or for whom the 
    investigations were conducted and which refers to the drug for which 
    the subsection (b) application was submitted effective before the 
    expiration of two years from September 24, 1984.

    (4) A drug manufactured in a pilot or other small facility may be 
used to demonstrate the safety and effectiveness of the drug and to 
obtain approval for the drug prior to manufacture of the drug in a 
larger facility, unless the Secretary makes a determination that a full 
scale production facility is necessary to ensure the safety or 
effectiveness of the drug.

(d) Grounds for refusing application; approval of application; 
        ``substantial evidence'' defined

    If the Secretary finds, after due notice to the applicant in 
accordance with subsection (c) of this section and giving him an 
opportunity for a hearing, in accordance with said subsection, that (1) 
the investigations, reports of which are required to be submitted to the 
Secretary pursuant to subsection (b) of this section, do not include 
adequate tests by all methods reasonably applicable to show whether or 
not such drug is safe for use under the conditions prescribed, 
recommended, or suggested in the proposed labeling thereof; (2) the 
results of such tests show that such drug is unsafe for use under such 
conditions or do not show that such drug is safe for use under such 
conditions; (3) the methods used in, and the facilities and controls 
used for, the manufacture, processing, and packing of such drug are 
inadequate to preserve its identity, strength, quality, and purity; (4) 
upon the basis of the information submitted to him as part of the 
application, or upon the basis of any other information before him with 
respect to such drug, he has insufficient information to determine 
whether such drug is safe for use under such conditions; or (5) 
evaluated on the basis of the information submitted to him as part of 
the application and any other information before him with respect to 
such drug, there is a lack of substantial evidence that the drug will 
have the effect it purports or is represented to have under the 
conditions of use prescribed, recommended, or suggested in the proposed 
labeling thereof; or (6) the application failed to contain the patent 
information prescribed by subsection (b) of this section; or (7) based 
on a fair evaluation of all material facts, such labeling is false or 
misleading in any particular; he shall issue an order refusing to 
approve the application. If, after such notice and opportunity for 
hearing, the Secretary finds that clauses (1) through (6) do not apply, 
he shall issue an order approving the application. As used in this 
subsection and subsection (e) of this section, the term ``substantial 
evidence'' means evidence consisting of adequate and well-controlled 
investigations, including clinical investigations, by experts qualified 
by scientific training and experience to evaluate the effectiveness of 
the drug involved, on the basis of which it could fairly and responsibly 
be concluded by such experts that the drug will have the effect it 
purports or is represented to have under the conditions of use 
prescribed, recommended, or suggested in the labeling or proposed 
labeling thereof. If the Secretary determines, based on relevant 
science, that data from one adequate and well-controlled clinical 
investigation and confirmatory evidence (obtained prior to or after such 
investigation) are sufficient to establish effectiveness, the Secretary 
may consider such data and evidence to constitute substantial evidence 
for purposes of the preceding sentence.

(e) Withdrawal of approval; grounds; immediate suspension upon finding 
        imminent hazard to public health

    The Secretary shall, after due notice and opportunity for hearing to 
the applicant, withdraw approval of an application with respect to any 
drug under this section if the Secretary finds (1) that clinical or 
other experience, tests, or other scientific data show that such drug is 
unsafe for use under the conditions of use upon the basis of which the 
application was approved; (2) that new evidence of clinical experience, 
not contained in such application or not available to the Secretary 
until after such application was approved, or tests by new methods, or 
tests by methods not deemed reasonably applicable when such application 
was approved, evaluated together with the evidence available to the 
Secretary when the application was approved, shows that such drug is not 
shown to be safe for use under the conditions of use upon the basis of 
which the application was approved; or (3) on the basis of new 
information before him with respect to such drug, evaluated together 
with the evidence available to him when the application was approved, 
that there is a lack of substantial evidence that the drug will have the 
effect it purports or is represented to have under the conditions of use 
prescribed, recommended, or suggested in the labeling thereof; or (4) 
the patent information prescribed by subsection (c) of this section was 
not filed within thirty days after the receipt of written notice from 
the Secretary specifying the failure to file such information; or (5) 
that the application contains any untrue statement of a material fact: 
Provided, That if the Secretary (or in his absence the officer acting as 
Secretary) finds that there is an imminent hazard to the public health, 
he may suspend the approval of such application immediately, and give 
the applicant prompt notice of his action and afford the applicant the 
opportunity for an expedited hearing under this subsection; but the 
authority conferred by this proviso to suspend the approval of an 
application shall not be delegated. The Secretary may also, after due 
notice and opportunity for hearing to the applicant, withdraw the 
approval of an application submitted under subsection (b) or (j) of this 
section with respect to any drug under this section if the Secretary 
finds (1) that the applicant has failed to establish a system for 
maintaining required records, or has repeatedly or deliberately failed 
to maintain such records or to make required reports, in accordance with 
a regulation or order under subsection (k) of this section or to comply 
with the notice requirements of section 360(k)(2) of this title, or the 
applicant has refused to permit access to, or copying or verification 
of, such records as required by paragraph (2) of such subsection; or (2) 
that on the basis of new information before him, evaluated together with 
the evidence before him when the application was approved, the methods 
used in, or the facilities and controls used for, the manufacture, 
processing, and packing of such drug are inadequate to assure and 
preserve its identity, strength, quality, and purity and were not made 
adequate within a reasonable time after receipt of written notice from 
the Secretary specifying the matter complained of; or (3) that on the 
basis of new information before him, evaluated together with the 
evidence before him when the application was approved, the labeling of 
such drug, based on a fair evaluation of all material facts, is false or 
misleading in any particular and was not corrected within a reasonable 
time after receipt of written notice from the Secretary specifying the 
matter complained of. Any order under this subsection shall state the 
findings upon which it is based.

(f) Revocation of order refusing, withdrawing or suspending approval of 
        application

    Whenever the Secretary finds that the facts so require, he shall 
revoke any previous order under subsection (d) or (e) of this section 
refusing, withdrawing, or suspending approval of an application and 
shall approve such application or reinstate such approval, as may be 
appropriate.

(g) Service of orders

    Orders of the Secretary issued under this section shall be served 
(1) in person by any officer or employee of the department designated by 
the Secretary or (2) by mailing the order by registered mail or by 
certified mail addressed to the applicant or respondent at his last-
known address in the records of the Secretary.

(h) Appeal from order

    An appeal may be taken by the applicant from an order of the 
Secretary refusing or withdrawing approval of an application under this 
section. Such appeal shall be taken by filing in the United States court 
of appeals or the circuit wherein such applicant resides or has his 
principal place of business, or in the United States Court of Appeals 
for the District of Columbia Circuit, within sixty days after the entry 
of such order, a written petition praying that the order of the 
Secretary be set aside. A copy of such petition shall be forthwith 
transmitted by the clerk of the court to the Secretary, or any officer 
designated by him for that purpose, and thereupon the Secretary shall 
certify and file in the court the record upon which the order complained 
of was entered, as provided in section 2112 of title 28. Upon the filing 
of such petition such court shall have exclusive jurisdiction to affirm 
or set aside such order, except that until the filing of the record the 
Secretary may modify or set aside his order. No objection to the order 
of the Secretary shall be considered by the court unless such objection 
shall have been urged before the Secretary or unless there were 
reasonable grounds for failure so to do. The finding of the Secretary as 
to the facts, if supported by substantial evidence, shall be conclusive. 
If any person shall apply to the court for leave to adduce additional 
evidence, and shall show to the satisfaction of the court that such 
additional evidence is material and that there were reasonable grounds 
for failure to adduce such evidence in the proceeding before the 
Secretary, the court may order such additional evidence to be taken 
before the Secretary and to be adduced upon the hearing in such manner 
and upon such terms and conditions as to the court may seem proper. The 
Secretary may modify his findings as to the facts by reason of the 
additional evidence so taken, and he shall file with the court such 
modified findings which, if supported by substantial evidence, shall be 
conclusive, and his recommendation, if any, for the setting aside of the 
original order. The judgment of the court affirming or setting aside any 
such order of the Secretary shall be final, subject to review by the 
Supreme Court of the United States upon certiorari or certification as 
provided in section 1254 of title 28. The commencement of proceedings 
under this subsection shall not, unless specifically ordered by the 
court to the contrary, operate as a stay of the Secretary's order.

(i) Exemptions of drugs for research; discretionary and mandatory 
        conditions; direct reports to Secretary

    (1) The Secretary shall promulgate regulations for exempting from 
the operation of the foregoing subsections of this section drugs 
intended solely for investigational use by experts qualified by 
scientific training and experience to investigate the safety and 
effectiveness of drugs. Such regulations may, within the discretion of 
the Secretary, among other conditions relating to the protection of the 
public health, provide for conditioning such exemption upon--
        (A) the submission to the Secretary, before any clinical testing 
    of a new drug is undertaken, of reports, by the manufacturer or the 
    sponsor of the investigation of such drug, of preclinical tests 
    (including tests on animals) of such drug adequate to justify the 
    proposed clinical testing;
        (B) the manufacturer or the sponsor of the investigation of a 
    new drug proposed to be distributed to investigators for clinical 
    testing obtaining a signed agreement from each of such investigators 
    that patients to whom the drug is administered will be under his 
    personal supervision, or under the supervision of investigators 
    responsible to him, and that he will not supply such drug to any 
    other investigator, or to clinics, for administration to human 
    beings; and
        (C) the establishment and maintenance of such records, and the 
    making of such reports to the Secretary, by the manufacturer or the 
    sponsor of the investigation of such drug, of data (including but 
    not limited to analytical reports by investigators) obtained as the 
    result of such investigational use of such drug, as the Secretary 
    finds will enable him to evaluate the safety and effectiveness of 
    such drug in the event of the filing of an application pursuant to 
    subsection (b) of this section.

    (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 investigation 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 investigation; 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 investigation (referred to in this 
paragraph as a ``clinical hold'') if the Secretary makes a determination 
described in subparagraph (B). The Secretary shall specify the basis for 
the clinical 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 determination described in 
this subparagraph with respect to a clinical hold is that--
        (i) the drug involved represents an unreasonable risk to the 
    safety of the persons who are the subjects of the clinical 
    investigation, taking into account the qualifications of the 
    clinical investigators, information about the drug, the design of 
    the clinical investigation, the condition for which the drug is to 
    be investigated, and the health status of the subjects involved; or
        (ii) the clinical hold should be issued for such other reasons 
    as the Secretary may by regulation establish (including reasons 
    established by regulation before November 21, 1997).

    (C) Any written request to the Secretary from the sponsor of an 
investigation that a clinical hold be removed shall receive 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.
    (4) Regulations under paragraph (1) 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 
representatives, except where it is not feasible or it is 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.

(j) Abbreviated new drug applications

    (1) Any person may file with the Secretary an abbreviated 
application for the approval of a new drug.
    (2)(A) An abbreviated application for a new drug shall contain--
        (i) information to show that the conditions of use prescribed, 
    recommended, or suggested in the labeling proposed for the new drug 
    have been previously approved for a drug listed under paragraph (7) 
    (hereinafter in this subsection referred to as a ``listed drug'');
        (ii)(I) if the listed drug referred to in clause (i) has only 
    one active ingredient, information to show that the active 
    ingredient of the new drug is the same as that of the listed drug;
        (II) if the listed drug referred to in clause (i) has more than 
    one active ingredient, information to show that the active 
    ingredients of the new drug are the same as those of the listed 
    drug, or
        (III) if the listed drug referred to in clause (i) has more than 
    one active ingredient and if one of the active ingredients of the 
    new drug is different and the application is filed pursuant to the 
    approval of a petition filed under subparagraph (C), information to 
    show that the other active ingredients of the new drug are the same 
    as the active ingredients of the listed drug, information to show 
    that the different active ingredient is an active ingredient of a 
    listed drug or of a drug which does not meet the requirements of 
    section 321(p) of this title, and such other information respecting 
    the different active ingredient with respect to which the petition 
    was filed as the Secretary may require;
        (iii) information to show that the route of administration, the 
    dosage form, and the strength of the new drug are the same as those 
    of the listed drug referred to in clause (i) or, if the route of 
    administration, the dosage form, or the strength of the new drug is 
    different and the application is filed pursuant to the approval of a 
    petition filed under subparagraph (C), such information respecting 
    the route of administration, dosage form, or strength with respect 
    to which the petition was filed as the Secretary may require;
        (iv) information to show that the new drug is bioequivalent to 
    the listed drug referred to in clause (i), except that if the 
    application is filed pursuant to the approval of a petition filed 
    under subparagraph (C), information to show that the active 
    ingredients of the new drug are of the same pharmacological or 
    therapeutic class as those of the listed drug referred to in clause 
    (i) and the new drug can be expected to have the same therapeutic 
    effect as the listed drug when administered to patients for a 
    condition of use referred to in clause (i);
        (v) information to show that the labeling proposed for the new 
    drug is the same as the labeling approved for the listed drug 
    referred to in clause (i) except for changes required because of 
    differences approved under a petition filed under subparagraph (C) 
    or because the new drug and the listed drug are produced or 
    distributed by different manufacturers;
        (vi) the items specified in clauses (B) through (F) of 
    subsection (b)(1) of this section;
        (vii) a certification, in the opinion of the applicant and to 
    the best of his knowledge, with respect to each patent which claims 
    the listed drug referred to in clause (i) or which claims a use for 
    such listed drug for which the applicant is seeking approval under 
    this subsection and for which information is required to be filed 
    under subsection (b) or (c) of this section--
            (I) that such patent information has not been filed,
            (II) that such patent has expired,
            (III) of the date on which such patent will expire, or
            (IV) that such patent is invalid or will not be infringed by 
        the manufacture, use, or sale of the new drug for which the 
        application is submitted; and

        (viii) if with respect to the listed drug referred to in clause 
    (i) information was filed under subsection (b) or (c) of this 
    section for a method of use patent which does not claim a use for 
    which the applicant is seeking approval under this subsection, a 
    statement that the method of use patent does not claim such a use.

The Secretary may not require that an abbreviated application contain 
information in addition to that required by clauses (i) through (viii).
    (B)(i) An applicant who makes a certification described in 
subparagraph (A)(vii)(IV) shall include in the application a statement 
that the applicant will give the notice required by clause (ii) to--
        (I) each owner of the patent which is the subject of the 
    certification or the representative of such owner designated to 
    receive such notice, and
        (II) the holder of the approved application under subsection (b) 
    of this section for the drug which is claimed by the patent or a use 
    of which is claimed by the patent or the representative of such 
    holder designated to receive such notice.

    (ii) The notice referred to in clause (i) shall state that an 
application, which contains data from bioavailability or bioequivalence 
studies, has been submitted under this subsection for the drug with 
respect to which the certification is made to obtain approval to engage 
in the commercial manufacture, use, or sale of such drug before the 
expiration of the patent referred to in the certification. Such notice 
shall include a detailed statement of the factual and legal basis of the 
applicant's opinion that the patent is not valid or will not be 
infringed.
    (iii) If an application is amended to include a certification 
described in subparagraph (A)(vii)(IV), the notice required by clause 
(ii) shall be given when the amended application is submitted.
    (C) If a person wants to submit an abbreviated application for a new 
drug which has a different active ingredient or whose route of 
administration, dosage form, or strength differ from that of a listed 
drug, such person shall submit a petition to the Secretary seeking 
permission to file such an application. The Secretary shall approve or 
disapprove a petition submitted under this subparagraph within ninety 
days of the date the petition is submitted. The Secretary shall approve 
such a petition unless the Secretary finds--
        (i) that investigations must be conducted to show the safety and 
    effectiveness of the drug or of any of its active ingredients, the 
    route of administration, the dosage form, or strength which differ 
    from the listed drug; or
        (ii) that any drug with a different active ingredient may not be 
    adequately evaluated for approval as safe and effective on the basis 
    of the information required to be submitted in an abbreviated 
    application.

    (3)(A) The Secretary shall issue guidance for the individuals who 
review applications submitted under paragraph (1), which shall relate to 
promptness in conducting the review, technical excellence, lack of bias 
and conflict of interest, and knowledge of regulatory and scientific 
standards, and 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 for a drug under this subsection if the 
sponsor or applicant makes a reasonable written request for a meeting 
for the purpose of reaching agreement on the design and size of 
bioavailability and bioequivalence studies needed for approval of such 
application. The sponsor or applicant shall provide information 
necessary for discussion and agreement on the design and size of such 
studies. Minutes of any such meeting shall be prepared by the Secretary 
and made available to the sponsor or applicant.
    (C) Any agreement regarding the parameters of design and size of 
bioavailability and bioequivalence studies of a drug under this 
paragraph that is 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 reviewing division, that a 
    substantial scientific issue essential to determining the safety or 
    effectiveness of the drug has been identified after the testing has 
    begun.

    (D) A decision under subparagraph (C)(ii) by the director 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 will document 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 unless such field or compliance office 
personnel demonstrate to the reviewing division why such decision should 
be modified.
    (F) No action by the reviewing division may be delayed because of 
the unavailability of information from or action by field personnel 
unless the reviewing division determines that a delay is necessary to 
assure the marketing of a safe and effective drug.
    (G) For purposes of this paragraph, the reviewing division is the 
division responsible for the review of an application for approval of a 
drug under this subsection (including scientific matters, chemistry, 
manufacturing, and controls).
    (4) Subject to paragraph (5), the Secretary shall approve an 
application for a drug unless the Secretary finds--
        (A) the methods used in, or the facilities and controls used 
    for, the manufacture, processing, and packing of the drug are 
    inadequate to assure and preserve its identity, strength, quality, 
    and purity;
        (B) information submitted with the application is insufficient 
    to show that each of the proposed conditions of use have been 
    previously approved for the listed drug referred to in the 
    application;
        (C)(i) if the listed drug has only one active ingredient, 
    information submitted with the application is insufficient to show 
    that the active ingredient is the same as that of the listed drug;
        (ii) if the listed drug has more than one active ingredient, 
    information submitted with the application is insufficient to show 
    that the active ingredients are the same as the active ingredients 
    of the listed drug, or
        (iii) if the listed drug has more than one active ingredient and 
    if the application is for a drug which has an active ingredient 
    different from the listed drug, information submitted with the 
    application is insufficient to show--
            (I) that the other active ingredients are the same as the 
        active ingredients of the listed drug, or
            (II) that the different active ingredient is an active 
        ingredient of a listed drug or a drug which does not meet the 
        requirements of section 321(p) of this title,

    or no petition to file an application for the drug with the 
    different ingredient was approved under paragraph (2)(C);
        (D)(i) if the application is for a drug whose route of 
    administration, dosage form, or strength of the drug is the same as 
    the route of administration, dosage form, or strength of the listed 
    drug referred to in the application, information submitted in the 
    application is insufficient to show that the route of 
    administration, dosage form, or strength is the same as that of the 
    listed drug, or
        (ii) if the application is for a drug whose route of 
    administration, dosage form, or strength of the drug is different 
    from that of the listed drug referred to in the application, no 
    petition to file an application for the drug with the different 
    route of administration, dosage form, or strength was approved under 
    paragraph (2)(C);
        (E) if the application was filed pursuant to the approval of a 
    petition under paragraph (2)(C), the application did not contain the 
    information required by the Secretary respecting the active 
    ingredient, route of administration, dosage form, or strength which 
    is not the same;
        (F) information submitted in the application is insufficient to 
    show that the drug is bioequivalent to the listed drug referred to 
    in the application or, if the application was filed pursuant to a 
    petition approved under paragraph (2)(C), information submitted in 
    the application is insufficient to show that the active ingredients 
    of the new drug are of the same pharmacological or therapeutic class 
    as those of the listed drug referred to in paragraph (2)(A)(i) and 
    that the new drug can be expected to have the same therapeutic 
    effect as the listed drug when administered to patients for a 
    condition of use referred to in such paragraph;
        (G) information submitted in the application is insufficient to 
    show that the labeling proposed for the drug is the same as the 
    labeling approved for the listed drug referred to in the application 
    except for changes required because of differences approved under a 
    petition filed under paragraph (2)(C) or because the drug and the 
    listed drug are produced or distributed by different manufacturers;
        (H) information submitted in the application or any other 
    information available to the Secretary shows that (i) the inactive 
    ingredients of the drug are unsafe for use under the conditions 
    prescribed, recommended, or suggested in the labeling proposed for 
    the drug, or (ii) the composition of the drug is unsafe under such 
    conditions because of the type or quantity of inactive ingredients 
    included or the manner in which the inactive ingredients are 
    included;
        (I) the approval under subsection (c) of this section of the 
    listed drug referred to in the application under this subsection has 
    been withdrawn or suspended for grounds described in the first 
    sentence of subsection (e) of this section, the Secretary has 
    published a notice of opportunity for hearing to withdraw approval 
    of the listed drug under subsection (c) of this section for grounds 
    described in the first sentence of subsection (e) of this section, 
    the approval under this subsection of the listed drug referred to in 
    the application under this subsection has been withdrawn or 
    suspended under paragraph (6), or the Secretary has determined that 
    the listed drug has been withdrawn from sale for safety or 
    effectiveness reasons;
        (J) the application does not meet any other requirement of 
    paragraph (2)(A); or
        (K) the application contains an untrue statement of material 
    fact.

    (5)(A) Within one hundred and eighty days of the initial receipt of 
an application under paragraph (2) or within such additional period as 
may be agreed upon by the Secretary and the applicant, the Secretary 
shall approve or disapprove the application.
    (B) The approval of an application submitted under paragraph (2) 
shall be made effective on the last applicable date determined under the 
following:
        (i) If the applicant only made a certification described in 
    subclause (I) or (II) of paragraph (2)(A)(vii) or in both such 
    subclauses, the approval may be made effective immediately.
        (ii) If the applicant made a certification described in 
    subclause (III) of paragraph (2)(A)(vii), the approval may be made 
    effective on the date certified under subclause (III).
        (iii) If the applicant made a certification described in 
    subclause (IV) of paragraph (2)(A)(vii), the approval shall be made 
    effective immediately unless an action is brought for infringement 
    of a patent which is the subject of the certification before the 
    expiration of forty-five days from the date the notice provided 
    under paragraph (2)(B)(i) is received. If such an action is brought 
    before the expiration of such days, the approval shall be made 
    effective upon the expiration of the thirty-month period beginning 
    on the date of the receipt of the notice provided under paragraph 
    (2)(B)(i) or such shorter or longer period as the court may order 
    because either party to the action failed to reasonably cooperate in 
    expediting the action, except that--
            (I) if before the expiration of such period the court 
        decides that such patent is invalid or not infringed, the 
        approval shall be made effective on the date of the court 
        decision,
            (II) if before the expiration of such period the court 
        decides that such patent has been infringed, the approval shall 
        be made effective on such date as the court orders under section 
        271(e)(4)(A) of title 35, or
            (III) if before the expiration of such period the court 
        grants a preliminary injunction prohibiting the applicant from 
        engaging in the commercial manufacture or sale of the drug until 
        the court decides the issues of patent validity and infringement 
        and if the court decides that such patent is invalid or not 
        infringed, the approval shall be made effective on the date of 
        such court decision.

    In such an action, each of the parties shall reasonably cooperate in 
    expediting the action. Until the expiration of forty-five days from 
    the date the notice made under paragraph (2)(B)(i) is received, no 
    action may be brought under section 2201 of title 28, for a 
    declaratory judgment with respect to the patent. Any action brought 
    under section 2201 shall be brought in the judicial district where 
    the defendant has its principal place of business or a regular and 
    established place of business.
        (iv) If the application contains a certification described in 
    subclause (IV) of paragraph (2)(A)(vii) and is for a drug for which 
    a previous application has been submitted under this subsection 
    continuing such a certification, the application shall be made 
    effective not earlier than one hundred and eighty days after--
            (I) the date the Secretary receives notice from the 
        applicant under the previous application of the first commercial 
        marketing of the drug under the previous application, or
            (II) the date of a decision of a court in an action 
        described in clause (iii) holding the patent which is the 
        subject of the certification to be invalid or not infringed,

    whichever is earlier.

    (C) If the Secretary decides to disapprove an application, the 
Secretary shall give the applicant notice of an opportunity for a 
hearing before the Secretary on the question of whether such application 
is approvable. If the applicant elects to accept the opportunity for 
hearing by written request within thirty days after such notice, such 
hearing shall commence not more than ninety days after the expiration of 
such thirty days unless the Secretary and the applicant otherwise agree. 
Any such hearing shall thereafter be conducted on an expedited basis and 
the Secretary's order thereon shall be issued within ninety days after 
the date fixed by the Secretary for filing final briefs.
    (D)(i) If an application (other than an abbreviated new drug 
application) submitted under subsection (b) of this section for a drug, 
no active ingredient (including any ester or salt of the active 
ingredient) of which has been approved in any other application under 
subsection (b) of this section, was approved during the period beginning 
January 1, 1982, and ending on September 24, 1984, the Secretary may not 
make the approval of an application submitted under this subsection 
which refers to the drug for which the subsection (b) application was 
submitted effective before the expiration of ten years from the date of 
the approval of the application under subsection (b) of this section.
    (ii) If an application submitted under subsection (b) of this 
section for a drug, no active ingredient (including any ester or salt of 
the active ingredient) of which has been approved in any other 
application under subsection (b) of this section, is approved after 
September 24, 1984, no application may be submitted under this 
subsection which refers to the drug for which the subsection (b) 
application was submitted before the expiration of five years from the 
date of the approval of the application under subsection (b) of this 
section, except that such an application may be submitted under this 
subsection after the expiration of four years from the date of the 
approval of the subsection (b) application if it contains a 
certification of patent invalidity or noninfringement described in 
subclause (IV) of paragraph (2)(A)(vii). The approval of such an 
application shall be made effective in accordance with subparagraph (B) 
except that, if an action for patent infringement is commenced during 
the one-year period beginning forty-eight months after the date of the 
approval of the subsection (b) application, the thirty-month period 
referred to in subparagraph (B)(iii) shall be extended by such amount of 
time (if any) which is required for seven and one-half years to have 
elapsed from the date of approval of the subsection (b) application.
    (iii) If an application submitted under subsection (b) of this 
section for a drug, which includes an active ingredient (including any 
ester or salt of the active ingredient) that has been approved in 
another application approved under subsection (b) of this section, is 
approved after September 24, 1984, and if such application contains 
reports of new clinical investigations (other than bioavailability 
studies) essential to the approval of the application and conducted or 
sponsored by the applicant, the Secretary may not make the approval of 
an application submitted under this subsection for the conditions of 
approval of such drug in the subsection (b) application effective before 
the expiration of three years from the date of the approval of the 
application under subsection (b) of this section for such drug.
    (iv) If a supplement to an application approved under subsection (b) 
of this section is approved after September 24, 1984, and the supplement 
contains reports of new clinical investigations (other than 
bioavailability studies) essential to the approval of the supplement and 
conducted or sponsored by the person submitting the supplement, the 
Secretary may not make the approval of an application submitted under 
this subsection for a change approved in the supplement effective before 
the expiration of three years from the date of the approval of the 
supplement under subsection (b) of this section.
    (v) If an application (or supplement to an application) submitted 
under subsection (b) of this section for a drug, which includes an 
active ingredient (including any ester or salt of the active ingredient) 
that has been approved in another application under subsection (b) of 
this section, was approved during the period beginning January 1, 1982, 
and ending on September 24, 1984, the Secretary may not make the 
approval of an application submitted under this subsection which refers 
to the drug for which the subsection (b) application was submitted or 
which refers to a change approved in a supplement to the subsection (b) 
application effective before the expiration of two years from September 
24, 1984.
    (6) If a drug approved under this subsection refers in its approved 
application to a drug the approval of which was withdrawn or suspended 
for grounds described in the first sentence of subsection (e) of this 
section or was withdrawn or suspended under this paragraph or which, as 
determined by the Secretary, has been withdrawn from sale for safety or 
effectiveness reasons, the approval of the drug under this subsection 
shall be withdrawn or suspended--
        (A) for the same period as the withdrawal or suspension under 
    subsection (e) of this section or this paragraph, or
        (B) if the listed drug has been withdrawn from sale, for the 
    period of withdrawal from sale or, if earlier, the period ending on 
    the date the Secretary determines that the withdrawal from sale is 
    not for safety or effectiveness reasons.

    (7)(A)(i) Within sixty days of September 24, 1984, the Secretary 
shall publish and make available to the public--
        (I) a list in alphabetical order of the official and proprietary 
    name of each drug which has been approved for safety and 
    effectiveness under subsection (c) of this section before September 
    24, 1984;
        (II) the date of approval if the drug is approved after 1981 and 
    the number of the application which was approved; and
        (III) whether in vitro or in vivo bioequivalence studies, or 
    both such studies, are required for applications filed under this 
    subsection which will refer to the drug published.

    (ii) Every thirty days after the publication of the first list under 
clause (i) the Secretary shall revise the list to include each drug 
which has been approved for safety and effectiveness under subsection 
(c) of this section or approved under this subsection during the thirty-
day period.
    (iii) When patent information submitted under subsection (b) or (c) 
of this section respecting a drug included on the list is to be 
published by the Secretary, the Secretary shall, in revisions made under 
clause (ii), include such information for such drug.
    (B) A drug approved for safety and effectiveness under subsection 
(c) of this section or approved under this subsection shall, for 
purposes of this subsection, be considered to have been published under 
subparagraph (A) on the date of its approval or September 24, 1984, 
whichever is later.
    (C) If the approval of a drug was withdrawn or suspended for grounds 
described in the first sentence of subsection (e) of this section or was 
withdrawn or suspended under paragraph (6) or if the Secretary 
determines that a drug has been withdrawn from sale for safety or 
effectiveness reasons, it may not be published in the list under 
subparagraph (A) or, if the withdrawal or suspension occurred after its 
publication in such list, it shall be immediately removed from such 
list--
        (i) for the same period as the withdrawal or suspension under 
    subsection (e) of this section or paragraph (6), or
        (ii) if the listed drug has been withdrawn from sale, for the 
    period of withdrawal from sale or, if earlier, the period ending on 
    the date the Secretary determines that the withdrawal from sale is 
    not for safety or effectiveness reasons.

A notice of the removal shall be published in the Federal Register.
    (8) For purposes of this subsection:
        (A) The term ``bioavailability'' means the rate and extent to 
    which the active ingredient or therapeutic ingredient is absorbed 
    from a drug and becomes available at the site of drug action.
        (B) A drug shall be considered to be bioequivalent to a listed 
    drug if--
            (i) the rate and extent of absorption of the drug do not 
        show a significant difference from the rate and extent of 
        absorption of the listed drug when administered at the same 
        molar dose of the therapeutic ingredient under similar 
        experimental conditions in either a single dose or multiple 
        doses; or
            (ii) the extent of absorption of the drug does not show a 
        significant difference from the extent of absorption of the 
        listed drug when administered at the same molar dose of the 
        therapeutic ingredient under similar experimental conditions in 
        either a single dose or multiple doses and the difference from 
        the listed drug in the rate of absorption of the drug is 
        intentional, is reflected in its proposed labeling, is not 
        essential to the attainment of effective body drug 
        concentrations on chronic use, and is considered medically 
        insignificant for the drug.

    (9) The Secretary shall, with respect to each application submitted 
under this subsection, maintain a record of--
        (A) the name of the applicant,
        (B) the name of the drug covered by the application,
        (C) the name of each person to whom the review of the chemistry 
    of the application was assigned and the date of such assignment, and
        (D) the name of each person to whom the bioequivalence review 
    for such application was assigned and the date of such assignment.

The information the Secretary is required to maintain under this 
paragraph with respect to an application submitted under this subsection 
shall be made available to the public after the approval of such 
application.

(k) Records and reports; required information; regulations and orders; 
        access to records

    (1) In the case of any drug for which an approval of an application 
filed under subsection (b) or (j) of this section is in effect, the 
applicant shall establish and maintain such records, and make such 
reports to the Secretary, of data relating to clinical experience and 
other data or information, received or otherwise obtained by such 
applicant with respect to such drug, as the Secretary may by general 
regulation, or by order with respect to such application, prescribe on 
the basis of a finding that such records and reports are necessary in 
order to enable the Secretary to determine, or facilitate a 
determination, whether there is or may be ground for invoking subsection 
(e) of this section. Regulations and orders issued under this subsection 
and under subsection (i) of this section shall have due regard for the 
professional ethics of the medical profession and the interests of 
patients and shall provide, where the Secretary deems it to be 
appropriate, for the examination, upon request, by the persons to whom 
such regulations or orders are applicable, of similar information 
received or otherwise obtained by the Secretary.
    (2) Every person required under this section to maintain records, 
and every person in charge or custody thereof, shall, upon request of an 
officer or employee designated by the Secretary, permit such officer or 
employee at all reasonable times to have access to and copy and verify 
such records.

(l) Public disclosure of safety and effectiveness data

    Safety and effectiveness data and information which has been 
submitted in an application under subsection (b) of this section for a 
drug and which has not previously been disclosed to the public shall be 
made available to the public, upon request, unless extraordinary 
circumstances are shown--
        (1) if no work is being or will be undertaken to have the 
    application approved,
        (2) if the Secretary has determined that the application is not 
    approvable and all legal appeals have been exhausted,
        (3) if approval of the application under subsection (c) of this 
    section is withdrawn and all legal appeals have been exhausted,
        (4) if the Secretary has determined that such drug is not a new 
    drug, or
        (5) upon the effective date of the approval of the first 
    application under subsection (j) of this section which refers to 
    such drug or upon the date upon which the approval of an application 
    under subsection (j) of this section which refers to such drug could 
    be made effective if such an application had been submitted.

(m) ``Patent'' defined

    For purposes of this section, the term ``patent'' means a patent 
issued by the United States Patent and Trademark Office.

(n) Scientific advisory panels

    (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 marketing of a drug under this section or 
section 262 of title 42, the Secretary shall establish panels of experts 
or use panels of experts established before November 21, 1997, or both.
    (2) The Secretary may delegate the appointment and oversight 
authority granted under section 394 of this title 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 the drugs to be referred to 
    the panel and who, to the extent feasible, possess skill and 
    experience in the development, manufacture, or utilization of such 
    drugs;
        (B) members with diverse expertise in such fields  as  clinical  
    and  administrative  medicine, pharmacy, pharmacology, 
    pharmacoeconomics, biological and physical sciences, and other 
    related professions;
        (C) a representative of consumer interests, and a representative 
    of interests of the drug manufacturing industry not directly 
    affected by the matter to be brought before the panel; and
        (D) two or more members who are specialists or have other 
    expertise in the particular disease or condition for which the drug 
    under review is proposed to be indicated.

Scientific, trade, and consumer organizations shall be afforded an 
opportunity to nominate individuals for appointment to the panels. No 
individual who is in the regular full-time employ of the United States 
and engaged in the administration of this chapter may be a voting member 
of any panel. The Secretary shall designate one of the members of each 
panel to serve as chairman thereof.
    (4) Each member of a panel shall publicly disclose all conflicts of 
interest that member may have with the work to be undertaken by the 
panel. No member of a panel may vote on any matter where the member or 
the immediate family of such member could gain financially from the 
advice given to the Secretary. The Secretary may grant a waiver of any 
conflict of interest requirement upon public disclosure of such conflict 
of interest if such waiver is necessary to afford the panel essential 
expertise, except that the Secretary may not grant a waiver for a member 
of a panel when the member's own scientific work is involved.
    (5) The Secretary shall, as appropriate, provide education and 
training to each new panel member before such member participates in a 
panel's activities, including education regarding requirements under 
this chapter and related regulations of the Secretary, and the 
administrative processes and procedures related to panel meetings.
    (6) Panel members (other than officers or employees of the United 
States), while attending meetings or conferences of a panel or otherwise 
engaged in its business, shall be entitled to receive compensation for 
each day so engaged, including traveltime, at rates to be fixed by the 
Secretary, but not to exceed the daily equivalent of the rate in effect 
for positions classified above grade GS-15 of the General Schedule. 
While serving away from their homes or regular places of business, panel 
members may be allowed travel expenses (including per diem in lieu of 
subsistence) as authorized by section 5703 of title 5, for persons in 
the Government service employed intermittently.
    (7) The Secretary shall ensure that scientific advisory panels meet 
regularly and at appropriate intervals so that any matter to be reviewed 
by such a panel can be presented to the panel not more than 60 days 
after the matter is ready for such review. Meetings of the panel may be 
held using electronic communication to convene the meetings.
    (8) Within 90 days after a scientific advisory panel makes 
recommendations on any matter under its review, the Food and Drug 
Administration official responsible for the matter shall review the 
conclusions and recommendations of the panel, and notify the affected 
persons of the final decision on the matter, or of the reasons that no 
such decision has been reached. Each such final decision shall be 
documented including the rationale for the decision.

(June 25, 1938, ch. 675, Sec. 505, 52 Stat. 1052; Pub. L. 86-507, 
Sec. 1(18), June 11, 1960, 74 Stat. 201; Pub. L. 87-781, title I, 
Secs. 102(b)-(d), 103(a), (b), 104(a)-(d)(2), Oct. 10, 1962, 76 Stat. 
781-783, 784, 785; Pub. L. 92-387, Sec. 4(d), Aug. 16, 1972, 86 Stat. 
562; Pub. L. 98-417, title I, Secs. 101, 102(a)-(b)(5), 103, 104, Sept. 
24, 1984, 98 Stat. 1585, 1592, 1593, 1597; Pub. L. 102-282, Sec. 5, May 
13, 1992, 106 Stat. 161; Pub. L. 103-80, Sec. 3(n), Aug. 13, 1993, 107 
Stat. 777; Pub. L. 105-115, title I, Secs. 115, 117, 119, 120, 124(a), 
Nov. 21, 1997, 111 Stat. 2313, 2315, 2316, 2318, 2324; Pub. L. 106-113, 
div. B, Sec. 1000(a)(9) [title IV, Sec. 4732(b)(11)], Nov. 29, 1999, 113 
Stat. 1536, 1501A-584.)

                       References in Text

    The General Schedule, referred to in subsec. (n)(6), is set out 
under section 5332 of Title 5, Government Organization and Employees.


                               Amendments

    1999--Subsec. (m). Pub. L. 106-113 substituted ``United States 
Patent and Trademark Office'' for ``Patent and Trademark Office of the 
Department of Commerce''.
    1997--Subsec. (b)(1). Pub. L. 105-115, Sec. 115(b), inserted at end 
``The Secretary shall, in consultation with the Director of the National 
Institutes of Health and with representatives of the drug manufacturing 
industry, review and develop guidance, as appropriate, on the inclusion 
of women and minorities in clinical trials required by clause (A).''
    Subsec. (b)(4). Pub. L. 105-115, Sec. 119(a), added par. (4).
    Subsec. (c)(4). Pub. L. 105-115, Sec. 124(a), added par. (4).
    Subsec. (d). Pub. L. 105-115, Sec. 115(a), inserted at end ``If the 
Secretary determines, based on relevant science, that data from one 
adequate and well-controlled clinical investigation and confirmatory 
evidence (obtained prior to or after such investigation) are sufficient 
to establish effectiveness, the Secretary may consider such data and 
evidence to constitute substantial evidence for purposes of the 
preceding sentence.''
    Subsec. (i). Pub. L. 105-115, Sec. 117, inserted ``(1)'' after 
``(i)'', redesignated former pars. (1) to (3) as subpars. (A) to (C), 
respectively, of par. (1), added pars. (2) to (4), and struck out 
closing provisions which read as follows: ``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 representatives, except where they deem it not feasible 
or, in their professional 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.''
    Subsec. (j)(2)(A)(i). Pub. L. 105-115, Sec. 119(b)(2)(A), 
substituted ``paragraph (7)'' for ``paragraph (6)''.
    Subsec. (j)(3). Pub. L. 105-115, Sec. 119(b)(1)(B), added par. (3). 
Former par. (3) redesignated (4).
    Subsec. (j)(4). Pub. L. 105-115, Sec. 119(b)(1)(A), (2)(B), 
redesignated par. (3) as (4) and in introductory provisions substituted 
``paragraph (5)'' for ``paragraph (4)''. Former par. (4) redesignated 
(5).
    Subsec. (j)(4)(I). Pub. L. 105-115, Sec. 119(b)(2)(C), substituted 
``paragraph (6)'' for ``paragraph (5)''.
    Subsec. (j)(5), (6). Pub. L. 105-115, Sec. 119(b)(1)(A), 
redesignated pars. (4) and (5) as (5) and (6), respectively. Former par. 
(6) redesignated (7).
    Subsec. (j)(7). Pub. L. 105-115, Sec. 119(b)(1)(A), (2)(D), 
redesignated par. (6) as (7) and in subpar. (C) substituted ``paragraph 
(6)'' for ``paragraph (5)'' in two places. Former par. (7) redesignated 
(8).
    Subsec. (j)(8), (9). Pub. L. 105-115, Sec. 119(b)(1)(A), 
redesignated pars. (7) and (8) as (8) and (9), respectively.
    Subsec. (n). Pub. L. 105-115, Sec. 120, added subsec. (n).
    1993--Subsec. (j)(6)(A)(ii). Pub. L. 103-80, Sec. 3(n)(1)(A), 
substituted ``Secretary'' for ``Secretry''.
    Subsec. (j)(6)(A)(iii). Pub. L. 103-80, Sec. 3(n)(1)(B), inserted 
comma after ``published by the Secretary''.
    Subsec. (k)(1). Pub. L. 103-80, Sec. 3(n)(2), substituted ``section. 
Regulations'' for ``section: Provided, however, That regulations''.
    1992--Subsec. (j)(8). Pub. L. 102-282 added par. (8).
    1984--Subsec. (a). Pub. L. 98-417, Sec. 102(b)(1), inserted ``or 
(j)'' after ``subsection (b)''.
    Subsec. (b). Pub. L. 98-417, Secs. 102(a)(1), 103(a), designated 
existing provisions of subsec. (b) as par. (1) thereof and redesignated 
existing cls. (1) through (6) of such par. (1) as cls. (A) through (F) 
thereof, respectively, inserted requirement that the applicant file with 
the application the patent number and the expiration date of any patent 
which claims the drug for which the applicant submitted the application 
or which claims a method of using such drug and with respect to which a 
claim of patent infringement could reasonably by asserted if a person 
not licensed by the owner engaged in the manufacture, use, or sale of 
the drug, that the applicant amend the application to include such 
information if an application is filed under this subsection for a drug 
and a patent which claims such drug or a method of using such drug is 
issued after the filing date but before approval of the application, and 
that upon approval of the application, the Secretary publish the 
information submitted, and added pars. (2) and (3).
    Subsec. (c). Pub. L. 98-417, Secs. 102(a)(2), (b)(2), 103(b), 
designated existing provisions of subsec. (c) as par. (1) thereof and in 
par. (1) as so designated substituted ``subsection (b) of this section'' 
for ``this subsection'' and redesignated former pars. (1) and (2) as 
subpars. (A) and (B), respectively, and added pars. (2) and (3).
    Subsec. (d)(6), (7). Pub. L. 98-417, Sec. 102(a)(3)(A), added cl. 
(6) relating to the failure of the application to contain the patent 
information prescribed by subsec. (b) of this section, and redesignated 
former cl. (6) as (7).
    Subsec. (e). Pub. L. 98-417, Sec. 102(a)(3)(B), in first sentence, 
added a new cl. (4) relating to the failure to file the patent 
information prescribed by subsec. (c) of this section within 30 days 
after the receipt of written notice from the Secretary specifying the 
failure to file such information, and redesignated former cl. (4) as 
(5).
    Pub. L. 98-417, Sec. 102(b)(3), (4), in second sentence, inserted in 
provisions preceding cl. (1) ``submitted under subsection (b) or (j) of 
this section'' and in cl. (1) substituted ``under subsection (k) of this 
section or to comply with the notice requirements of section 360(k)(2) 
of this title'' for ``under subsection (j) of this section or to comply 
with the notice requirements of section 360(j)(2) of this title''.
    Subsecs. (j), (k). Pub. L. 98-417, Sec. 101, added subsec. (j) and 
redesignated former subsec. (j) as (k).
    Subsec. (k)(1). Pub. L. 98-417, Sec. 102(b)(5), substituted ``under 
subsection (b) or (j) of this section'' for ``pursuant to this 
section''.
    Subsecs. (l), (m). Pub. L. 98-417, Sec. 104, added subsecs. (l) and 
(m).
    1972--Subsec. (e). Pub. L. 92-387 inserted ``or to comply with the 
notice requirements of section 360(j)(2) of this title'' in cl. (1) of 
second sentence relating to the maintenance of records.
    1962--Subsec. (a). Pub. L. 87-781, Sec. 104(a), inserted ``an 
approval of'' before ``an application''.
    Subsec. (b). Pub. L. 87-781, Sec. 102(b), inserted ``and whether 
such drug is effective in use'' after ``is safe for use''.
    Subsec. (c). Pub. L. 87-781, Sec. 104(b), substituted provisions 
requiring the Secretary, within 180 days after filing an application, or 
such additional period as the Secretary and the applicant agree upon, to 
either approve the application, if meeting the requirements of subsec. 
(d) of this section, or give notice of opportunity for hearing on 
question of whether such application is approvable, and providing that 
if applicant requests hearing in writing within 30 days, the hearing 
shall begin within 90 days after expiration of said 30 days, unless the 
Secretary and applicant agree otherwise, that such hearing shall be 
expedited, and that the Secretary's order shall be issued within 90 days 
after date for filing final briefs, for provisions which had an 
application become effective on the sixtieth day after filing thereof 
unless prior thereto the Secretary postponed the date by written notice 
to such time, but not more than 180 days after filing, as the Secretary 
deemed necessary to study and investigate the application.
    Subsec. (d). Pub. L. 87-781, Sec. 102(c), inserted references to 
subsec. (c), added cls. (5) and (6), provided that if after notice and 
opportunity for hearing, the Secretary finds that cls. (1) to (6) do not 
apply, he shall approve the application, and defined ``substantial 
evidence'' as used in this subsection and subsec. (e) of this section.
    Subsec. (e). Pub. L. 87-781, Sec. 102(d), amended subsec. (e) 
generally, and among other changes, directed the Secretary to withdraw 
approval of an application if by tests, other scientific data or 
experience, or new evidence of clinical experience not contained in the 
application or available at the time of its approval, the drug is shown 
to be unsafe, or on the basis of new information, there is shown a lack 
of substantial evidence that the drug has the effect it is represented 
to have, and provided that if the Secretary, or acting Secretary, finds 
there is an imminent hazard to the public health, he may suspend 
approval immediately, notify the applicant, and give him opportunity for 
an expedited hearing, that the Secretary may withdraw approval if the 
applicant fails to establish a system for maintaining required records, 
or has repeatedly or deliberately failed to maintain records and make 
reports, or has refused access to, or copying or verification of such 
records, or if the Secretary finds on new evidence that the methods, 
facilities and controls in the manufacturing, processing, and packing 
are inadequate to assure and preserve the drugs' identity, strength, 
quality and purity, and were not made adequate within a reasonable time 
after receipt of written notice thereof, or finds on new evidence, that 
the labeling is false or misleading and was not corrected within a 
reasonable time after receipt of written notice thereof.
    Subsec. (f). Pub. L. 87-781, Sec. 104(c), substituted provisions 
requiring the Secretary to revoke any previous order under subsecs. (d) 
or (e) of this section refusing, withdrawing, or suspending approval of 
an application and to approve such application or reinstate such 
approval, for provisions which required him to revoke an order refusing 
effectiveness to an application.
    Subsec. (h). Pub. L. 87-781, Sec. 104(d)(1), (2), inserted ``as 
provided in section 2112 of title 28'', and ``except that until the 
filing of the record the Secretary may modify or set aside his order'', 
substituted ``or withdrawing approval of an application under this 
section'' for ``to permit the application to become effective, or 
suspending the effectiveness of the application'', ``United States court 
of appeals for the circuit'' for ``district court of the United States 
within any district'', ``Court of Appeals for the District of Columbia 
Circuit'' for ``District Court for the District of Columbia'', 
``transmitted by the clerk of the court to'' for ``served upon'', and 
``by the Supreme Court of the United States upon certiorari or 
certification as provided in section 1254 of title 28'' for ``as 
provided in sections 225, 346, and 347 of title 28, as amended, and in 
section 7, as amended, of the Act entitled `An Act to establish a Court 
of Appeals for the District of Columbia', approved February 9, 1893'', 
and eliminated ``upon'' before ``any officer designated'', ``a 
transcript of'' before ``the record'' and ``and decree'' before ``of the 
court affirming''.
    Subsec. (i). Pub. L. 87-781, Sec. 103(b), inserted ``the foregoing 
subsections of'' after ``operation of'', and ``and effectiveness'' after 
``safety'', and provided that the regulations may condition exemptions 
upon the submission of reports of preclinical tests to justify the 
proposed clinical testing, upon the obtaining by the manufacturer or 
sponsor of the investigation of a new drug of a signed agreement from 
each of the investigators that patients to whom the drug is administered 
will be under his supervision or under investigators responsible to him, 
and that he will not supply such drug to any other investigator, or to 
clinics, for administration to human beings, or upon the establishment 
and maintenance of records and reports of data obtained by the 
investigational use of such drug, as the Secretary finds will enable him 
to evaluate the safety and effectiveness of such drug, and provided that 
the regulations shall condition an exemption upon the manufacturer or 
sponsor of the investigation requiring that experts using such drugs 
certify that they will inform humans to whom such drugs or any controls 
connected therewith are administered, or their representatives, and will 
obtain the consent of such people where feasible and not contrary to the 
best interests of such people, and that reports on the investigational 
use of drugs are not required to be submitted directly to the Secretary.
    Subsec. (j). Pub. L. 87-781, Sec. 103(a), added subsec. (j).
    1960--Subsec. (g). Pub. L. 86-507 inserted ``or by certified mail'' 
after ``registered mail''.


                    Effective Date of 1999 Amendment

    Amendment by Pub. L. 106-113 effective 4 months after Nov. 29, 1999, 
see section 1000(a)(9) [title IV, Sec. 4731] of Pub. L. 106-113, set out 
as a note under section 1 of Title 35, Patents.


                    Effective Date of 1997 Amendment

    Amendment by Pub. L. 105-115 effective 90 days after Nov. 21, 1997, 
except as otherwise provided, see section 501 of Pub. L. 105-115, set 
out as a note under section 321 of this title.


                    Effective Date of 1984 Amendment

    Section 105 of Pub. L. 98-417 provided that:
    ``(a) The Secretary of Health and Human Services shall promulgate, 
in accordance with the notice and comment requirements of section 553 of 
title 5, United States Code, such regulations as may be necessary for 
the administration of section 505 of the Federal Food, Drug, and 
Cosmetic Act [this section], as amended by sections 101, 102, and 103 of 
this Act, within one year of the date of enactment of this Act [Sept. 
24, 1984].
    ``(b) During the period beginning sixty days after the date of the 
enactment of this Act [Sept. 24, 1984], and ending on the date 
regulations promulgated under subsection (a) take effect, abbreviated 
new drug applications may be submitted in accordance with the provisions 
of section 314.2 of title 21 of the Code of Federal Regulations and 
shall be considered as suitable for any drug which has been approved for 
safety and effectiveness under section 505(c) of the Federal Food, Drug, 
and Cosmetic Act [subsec. (c) of this section] before the date of the 
enactment of this Act. If any such provision is inconsistent with the 
requirements of section 505(j) of the Federal Food, Drug, and Cosmetic 
Act, the Secretary shall consider the application under the applicable 
requirements of such section. The Secretary of Health and Human Services 
may not approve such an abbreviated new drug application which is filed 
for a drug which is described in sections 505(c)(3)(D) and 505(j)(4)(D) 
of the Federal Food, Drug, and Cosmetic Act, except in accordance with 
such section.''


                    Effective Date of 1972 Amendment

    Amendment by Pub. L. 92-387 effective on first day of sixth month 
beginning after Aug. 16, 1972, see section 5 of Pub. L. 92-387, set out 
as a note under section 360 of this title.


                    Effective Date of 1962 Amendment

    Amendment by Pub. L. 87-781 effective on first day of seventh 
calendar month following October 1962, see section 107 of Pub. L. 87-
781, set out as a note under section 321 of this title.


              Construction of Amendments by Pub. L. 102-282

    Amendment by Pub. L. 102-282 not to preclude any other civil, 
criminal, or administrative remedy provided under Federal or State law, 
including any private right of action against any person for the same 
action subject to any action or civil penalty under an amendment made by 
Pub. L. 102-282, see section 7 of Pub. L. 102-282, set out as a note 
under section 335a of this title.

                          Transfer of Functions

    For transfer of functions of Federal Security Administrator to 
Secretary of Health, Education, and Welfare [now Health and Human 
Services], and of Food and Drug Administration in the Department of 
Agriculture to Federal Security Agency, see note set out under section 
41 of this title.


                Data Requirements for Drugs and Biologics

    Section 118 of Pub. L. 105-115 provided that: ``Within 12 months 
after the date of enactment of this Act [Nov. 21, 1997], the Secretary 
of Health and Human Services, acting through the Commissioner of Food 
and Drugs, shall issue guidance that describes when abbreviated study 
reports may be submitted, in lieu of full reports, with a new drug 
application under section 505(b) of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 355(b)) and with a biologics license application under 
section 351 of the Public Health Service Act (42 U.S.C. 262) for certain 
types of studies. Such guidance shall describe the kinds of studies for 
which abbreviated reports are appropriate and the appropriate 
abbreviated report formats.''


    Requirements for Review of Approval Procedures and Current Good 
        Manufacturing Practices for Positron Emission Technology

    Section 121(c) of Pub. L. 105-115 provided that:
    ``(1) Procedures and requirements.--
        ``(A) In general.--In order to take account of the special 
    characteristics of positron emission tomography drugs and the 
    special techniques and processes required to produce these drugs, 
    not later than 2 years after the date of enactment of this Act [Nov. 
    21, 1997], the Secretary of Health and Human Services shall 
    establish--
            ``(i) appropriate procedures for the approval of positron 
        emission tomography drugs pursuant to section 505 of the Federal 
        Food, Drug, and Cosmetic Act (21 U.S.C. 355); and
            ``(ii) appropriate current good manufacturing practice 
        requirements for such drugs.
        ``(B) Considerations and consultation.--In establishing the 
    procedures and requirements required by subparagraph (A), the 
    Secretary of Health and Human Services shall take due account of any 
    relevant differences between not-for-profit institutions that 
    compound the drugs for their patients and commercial manufacturers 
    of the drugs. Prior to establishing the procedures and requirements, 
    the Secretary of Health and Human Services shall consult with 
    patient advocacy groups, professional associations, manufacturers, 
    and physicians and scientists licensed to make or use positron 
    emission tomography drugs.
    ``(2) Submission of new drug applications and abbreviated new drug 
applications.--
        ``(A) In general.--Except as provided in subparagraph (B), the 
    Secretary of Health and Human Services shall not require the 
    submission of new drug applications or abbreviated new drug 
    applications under subsection (b) or (j) of section 505 (21 U.S.C. 
    355), for compounded positron emission tomography drugs that are not 
    adulterated drugs described in section 501(a)(2)(C) of the Federal 
    Food, Drug, and Cosmetic Act (21 U.S.C. 351(a)(2)(C)) (as amended by 
    subsection (b)), for a period of 4 years after the date of enactment 
    of this Act [Nov. 21, 1997], or for 2 years after the date on which 
    the Secretary establishes procedures and requirements under 
    paragraph (1), whichever is longer.
        ``(B) Exception.--Nothing in this Act [see Short Title of 1997 
    Amendment note set out under section 301 of this title] shall 
    prohibit the voluntary submission of such applications or the review 
    of such applications by the Secretary of Health and Human Services. 
    Nothing in this Act shall constitute an exemption for a positron 
    emission tomography drug from the requirements of regulations issued 
    under section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 
    U.S.C. 355(i)).''


        ``Compounded Positron Emission Topography Drug'' Defined

    Section 121(e) of Pub. L. 105-115 provided that: ``As used in this 
section [amending sections 321 and 351 of this title and enacting 
provisions set out as notes under this section and section 351 of this 
title], the term `compounded positron emission tomography drug' has the 
meaning given the term in section 201 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 321).''


                  Requirements for Radiopharmaceuticals

    Section 122 of Pub. L. 105-115 provided that:
    ``(a) Requirements.--
        ``(1) Regulations.--
            ``(A) Proposed regulations.--Not later than 180 days after 
        the date of enactment of this Act [Nov. 21, 1997], the Secretary 
        of Health and Human Services, after consultation with patient 
        advocacy groups, associations, physicians licensed to use 
        radiopharmaceuticals, and the regulated industry, shall issue 
        proposed regulations governing the approval of 
        radiopharmaceuticals. The regulations shall provide that the 
        determination of the safety and effectiveness of such a 
        radiopharmaceutical under section 505 of the Federal Food, Drug, 
        and Cosmetic Act (21 U.S.C. 355) or section 351 of the Public 
        Health Service Act (42 U.S.C. 262) shall include consideration 
        of the proposed use of the radiopharmaceutical in the practice 
        of medicine, the pharmacological and toxicological activity of 
        the radiopharmaceutical (including any carrier or ligand 
        component of the radiopharmaceutical), and the estimated 
        absorbed radiation dose of the radiopharmaceutical.
            ``(B) Final regulations.--Not later than 18 months after the 
        date of enactment of this Act, the Secretary shall promulgate 
        final regulations governing the approval of the 
        radiopharmaceuticals.
        ``(2) Special rule.--In the case of a radiopharmaceutical, the 
    indications for which such radiopharmaceutical is approved for 
    marketing may, in appropriate cases, refer to manifestations of 
    disease (such as biochemical, physiological, anatomic, or 
    pathological processes) common to, or present in, one or more 
    disease states.
    ``(b) Definition.--In this section, the term `radiopharmaceutical' 
means--
        ``(1) an article--
            ``(A) that is intended for use in the diagnosis or 
        monitoring of a disease or a manifestation of a disease in 
        humans; and
            ``(B) that exhibits spontaneous disintegration of unstable 
        nuclei with the emission of nuclear particles or photons; or
        ``(2) any nonradioactive reagent kit or nuclide generator that 
    is intended to be used in the preparation of any such article.''


                              Special Rule

    Section 123(f) of Pub. L. 105-115 provided that: ``The Secretary of 
Health and Human Services shall take measures to minimize differences in 
the review and approval of products required to have approved biologics 
license applications under section 351 of the Public Health Service Act 
(42 U.S.C. 262) and products required to have approved new drug 
applications under section 505(b)(1) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 355(b)(1)).''


                               Transition

    Section 125(d) of Pub. L. 105-115 provided that:
    ``(1) In general.--An application that was approved by the Secretary 
of Health and Human Services before the date of the enactment of this 
Act [Nov. 21, 1997] for the marketing of an antibiotic drug under 
section 507 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 357), 
as in effect on the day before the date of the enactment of this Act, 
shall, on and after such date of enactment, be considered to be an 
application that was submitted and filed under section 505(b) of such 
Act (21 U.S.C. 355(b)) and approved for safety and effectiveness under 
section 505(c) of such Act (21 U.S.C. 355(c)), except that if such 
application for marketing was in the form of an abbreviated application, 
the application shall be considered to have been filed and approved 
under section 505(j) of such Act (21 U.S.C. 355(j)).
    ``(2) Exception.--The following subsections of section 505 (21 
U.S.C. 355) shall not apply to any application for marketing in which 
the drug that is the subject of the application contains an antibiotic 
drug and the antibiotic drug was the subject of any application for 
marketing received by the Secretary of Health and Human Services under 
section 507 of such Act (21 U.S.C. 357) before the date of the enactment 
of this Act [Nov. 21, 1997]:
        ``(A)(i) Subsections (c)(2), (d)(6), (e)(4), (j)(2)(A)(vii), 
    (j)(2)(A)(viii), (j)(2)(B), (j)(4)(B), and (j)(4)(D); and
        ``(ii) The third and fourth sentences of subsection (b)(1) 
    (regarding the filing and publication of patent information); and
        ``(B) Subsections (b)(2)(A), (b)(2)(B), (b)(3), and (c)(3) if 
    the investigations relied upon by the applicant for approval of the 
    application were not conducted by or for the applicant and for which 
    the applicant has not obtained a right of reference or use from the 
    person by or for whom the investigations were conducted.
    ``(3) Publication.--For purposes of this section, the Secretary is 
authorized to make available to the public the established name of each 
antibiotic drug that was the subject of any application for marketing 
received by the Secretary for Health and Human Services under section 
507 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 357) before 
the date of enactment of this Act [Nov. 21, 1997].''


                     Termination of Advisory Panels

    Advisory panels established after Jan. 5, 1973, to terminate not 
later than the expiration of the 2-year period beginning on the date of 
their establishment, unless, in the case of a panel established by the 
President or an officer of the Federal Government, such panel is renewed 
by appropriate action prior to the expiration of such 2-year period, or 
in the case of a panel established by Congress, its duration is 
otherwise provided for by law. See sections 3(2) and 14 of Pub. L. 92-
463, Oct. 6, 1972, 86 Stat. 770, 776, set out in the Appendix to Title 
5, Government Organization and Employees.


                 Appeals Taken Prior to October 10, 1962

    Section 104(d)(3) of Pub. L. 87-781 made amendments to subsec. (h) 
of this section inapplicable to any appeal taken prior to Oct. 10, 1962.

                  Section Referred to in Other Sections

    This section is referred to in sections 321, 331, 333, 334, 335a, 
352, 353, 353a, 355a, 356, 356a, 356c, 360, 360b, 360j, 360aa to 360ee, 
360aaa, 360bbb, 360bbb-1, 374, 379g, 379h, 379r, 381, 382, 384, 802, 
811, 827 of this title; title 10 section 1107; title 26 section 45C; 
title 28 section 2201; title 35 sections 155A, 156, 271; title 42 
sections 236, 262, 282, 300cc-12, 300cc-13, 300cc-17, 1395y, 1396r-8.
