I 
108TH CONGRESS 
2D SESSION 
H. R. 4598
To provide for the establishment of certain restrictions with respect to drugs 
containing isotretinoin (including the drug marketed as Accutane). 
IN THE HOUSE OF REPRESENTATIVES 
JUNE 16, 2004
Mr. STUPAK (for himself, Mr. SMITH of New Jersey, Mr. WELDON of Florida, 
Ms. KILPATRICK, Mr. WAMP, Ms. DEGETTE, Mr. BURTON of Indiana, 
Ms. DELAURO, Mr. DOYLE, Mr. BACA, and Mr. GORDON) introduced the 
following bill; which was referred to the Committee on Energy and Com-
merce 
A BILL 
To provide for the establishment of certain restrictions with 
respect to drugs containing isotretinoin (including the 
drug marketed as Accutane).
Be it enacted by the Senate and House of Representa-
tives of the United States of America in Congress assembled, 
SECTION 1. SHORT TITLE. 
This Act may be cited as the ‘‘Accutane Safety and 
Risk Management Act’’.
SEC. 2. FEDERAL FOOD, DRUG, AND COSMETIC ACT; RE-
STRICTIONS 
REGARDING 
DRUG 
ISOTRETINOIN. 
(a) IN GENERAL.—Not later than the expiration of 
the 30-day period beginning on the date of the enactment 
of this Act, the Secretary of Health and Human Services 
(referred to in this Act as the ‘‘Secretary’’), acting 
through the Commissioner of Food and Drugs, shall with-
draw the approval under section 505 of the Federal Food, 
Drug, and Cosmetic Act of each application for a drug 
that contains isotretinoin as an active ingredient (includ-
ing the drug marketed as Accutane). During or after such 
period, any holder of an application that is subject to the 
preceding sentence may file with the Secretary a supple-
mental application for such drug, and the Secretary may 
approve the supplemental application in accordance with 
subsection (b). 
(b) RESTRICTIONS.—Any approval by the Secretary 
of a supplemental application for a drug containing 
isotretinoin pursuant to subsection (a) shall provide that 
such drug is being approved as a drug subject to subpart 
H of part 314 of title 21, Code of Federal Regulations. 
The Secretary shall under such subpart H establish re-
strictions on the distribution of the drug. Such restrictions 
shall require that distribution of the drug under all the 
approved supplemental applications be exclusively through
a single program, approved by the Secretary, that provides 
for the distribution of the drug in accordance with the fol-
lowing conditions: 
(1) Distribution of the drug by manufacturers 
is directly to pharmacists (without the involvement 
of entities engaged in the wholesale distribution of 
drugs), and each pharmacist receiving the drug is in 
compliance with the following: 
(A) The pharmacist has registered with the 
program. 
(B) The pharmacist has received education 
on potential side effects of the drug relating to 
birth defects and mental health or behavioral 
issues that, as of the day before the date of the 
enactment of this Act, were described on the 
approved labeling for the drug (including de-
pression, suicidal ideation, suicide attempts, 
suicide, and aggressive or violent behavior). 
(C) The pharmacist agrees that the drug 
will be dispensed only pursuant to prescriptions 
issued by practitioners at treatment centers cer-
tified under paragraph (2). 
(D) The pharmacist has signed and filed 
with the program a statement that the phar-
macist understands the conditions for participa-
tion in the program as a pharmacist, and will 
maintain compliance with the agreement de-
scribed in subparagraph (C) and otherwise com-
ply with applicable conditions. 
(2) The program certifies clinics and medical 
offices as treatment centers regarding the drug, 
makes the certifications in accordance with the con-
ditions described in subsection (c), provides that the 
certifications are effective for one year, and main-
tains a registry of treatment centers for which cer-
tifications are in effect. 
(3) The program develops and makes available 
to practitioners materials for educating patients on 
the drug, including managing the risks associated 
with the drug, and such materials include a ques-
tionnaire, to be completed monthly by patients, that 
warns patients of the adverse side effects described 
in paragraph (1)(B) and monitors for the develop-
ment of any such effects in patients. 
(4) The drug is prescribed for a patient by a 
practitioner only in accordance with the following: 
(A) The drug is prescribed for severe, re-
calcitrant nodular acne that is unresponsive to 
conventional therapy, including antibiotics.
(B) The patient is registered with the pro-
gram. 
(C) Using the materials referred to in 
paragraph (3), the practitioner educates the pa-
tient on the drug, including providing one-on-
one, in-person counseling. 
(D) The practitioner provides to the pa-
tient the questionnaire referred to in paragraph 
(3), and the patient completes the question-
naire. 
(E) The patient signs a statement pro-
viding the informed consent of the patient to 
undergo treatment with the drug (or a parent 
or guardian of the patient signs the statement, 
in the case of a patient who is a minor or other-
wise lacks legal capacity). 
(F) The patient undergoes the appropriate 
blood tests. 
(G) In the case of a female patient—
(i) the education under subparagraph 
(C) includes education on the need to avoid 
becoming pregnant while being treated 
with the drug; and 
(ii) the practitioner determines that 
the patient is not pregnant, as indicated by
an electronic verification, provided to the 
practitioner by an accredited laboratory, 
that the patient has undergone a preg-
nancy test and received a negative result. 
(H) In the case of a male patient, the edu-
cation under subparagraph (C) includes edu-
cation on the need to avoid impregnating 
women while being treated with the drug. 
(I) The prescription is issued only after 
compliance with subparagraphs (B) through 
(H). 
(J) The prescription is for a 30-day supply 
of the drug, with no refills. 
(K) Each further prescription for the drug 
is issued by the practitioner to the patient only 
pursuant to another in-person consultation with 
the practitioner, and prior to issuing the pre-
scription, compliance with subparagraphs (C) 
through (I) is repeated. 
(L) The patient undergoes the appropriate 
blood tests 30 days after the conclusion of 
treatment with the drug. 
(5) Such additional conditions as the Secretary 
may by regulation determine to be necessary to pro-
tect the public health with respect to the drug.
(c) CERTIFICATION OF TREATMENT CENTERS.—For 
purposes of subsection (b)(2), the conditions for the pro-
gram to certify a clinic or medical office as a treatment 
center regarding a drug containing isotretinoin are as fol-
lows: 
(1) The program determines that each of the 
practitioners at the clinic or office who will prescribe 
the drug is in compliance with the following: 
(A) The practitioner is authorized under 
the law of the State involved to administer pre-
scription drugs. 
(B) The practitioner has registered with 
the program and received education on the po-
tential side effects referred to in subsection 
(b)(1)(B). 
(C) The practitioner agrees as follows: 
(i) The practitioner will prescribe the 
drug for a patient in accordance with sub-
section (b)(4). 
(ii) If a female patient being treated 
with the drug becomes pregnant, the prac-
titioner will immediately report the preg-
nancy to the program and provide follow-
up in accordance with the program.
(iii) The practitioner will not issue 
prescriptions for the drug by telephone or 
facsimile transmission, or through the 
Internet. 
(iv) The practitioner will—
(I) report to the Secretary any 
information received by the practi-
tioner on adverse events that are asso-
ciated with the use of the drug by pa-
tients of the practitioner; and 
(II) submit such reports quar-
terly, except in the case of a patient 
death associated with the drug, in 
which case the report will be sub-
mitted immediately, but in no case 
later than 15 days after the date on 
which the practitioner learns of the 
death. 
(D) The practitioner has signed and filed 
with the program a statement that the practi-
tioner understands the conditions for participa-
tion in the program as a practitioner, and will 
maintain compliance with the agreements de-
scribed in subparagraph (C) and otherwise com-
ply with applicable conditions.
(2) After the initial certification of the clinic or 
office, the program renews a certification for addi-
tional-one year periods only if the program has con-
ducted an evaluation to determine whether, during 
the preceding one-year period, each practitioner at 
the center who prescribes the drug has maintained 
substantial compliance with applicable conditions of 
the program. 
(3) Such additional conditions as the Secretary 
may by regulation determine to be necessary to pro-
tect the public health with respect to the drug. 
(d) MONITORING
BY SECRETARY.—The Secretary 
shall monitor the distribution of drugs containing 
isotretinoin under supplemental applications approved 
under subsection (b), including the prescribing and dis-
pensing of the drug, to determine whether the drug is 
being distributed in accordance with the program ap-
proved by the Secretary under such subsection. 
SEC. 3. REPORTING OF ADVERSE EVENTS BY MANUFAC-
TURERS AND DISTRIBUTORS. 
(a) IN GENERAL.—Each person who is a manufac-
turer or distributor of a drug containing isotretinoin shall 
report to the Secretary any information received by such 
person on adverse events that are associated with such 
drug. In any case in which an individual reports an ad-
verse event to such person and states that the individual 
believes the drug is a factor in the event, the person shall 
consider the event to be associated with the drug for pur-
poses of the preceding sentence. 
(b) TIMEFRAME
FOR REPORTING.—A person de-
scribed in subsection (a) shall submit reports under such 
subsection to the Secretary on a quarterly basis, except 
that in the case of a death associated with isotretinoin, 
the report shall be submitted immediately, but in no case 
later than 15 days after the date on which the person 
learns of the death. 
SEC. 4. FURTHER STUDIES. 
(a) IN GENERAL.—The Secretary, in consultation 
with the Director of the Centers for Disease Control and 
Prevention, the Director of the National Institutes of 
Health, and the Director of the National Institute of Men-
tal Health, shall continue to conduct and support appro-
priate studies to explore, in adolescents and adults—
(1) the effects of isotretinoin and retinoid acid 
on the central nervous system, including the brain; 
and 
(2) the behavioral effects of isotretinoin, includ-
ing depression, suicidal ideation, suicide attempts, 
suicide, and aggressive or violent behavior.
(b) AUTHORIZATION OF APPROPRIATIONS.—For the 
purpose of studies under subsection (a), there are author-
ized to be appropriated such sums as may be necessary 
for fiscal year 2005 and each subsequent fiscal year, in 
addition to any other authorizations of appropriations that 
are available for such purpose.
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