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 Commerce 

A BILL

To provide for the establishment of certain restrictions with 

respect to drugs containing isotretinoin (including the 

drug marketed as Accutane).

1 Be it enacted by the Senate and House of Representa2 tives of the United States of America in Congress assembled,

3 SECTION 1. SHORT TITLE. 

4 This Act may be cited as the ‘‘Accutane Safety and 

5 Risk Management Act’’. 
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1 SEC. 2. FEDERAL FOOD, DRUG, AND COSMETIC ACT; RE2 STRICTIONS REGARDING DRUG 

3 ISOTRETINOIN. 

4 (a) IN GENERAL.—Not later than the expiration of 

5 the 30-day period beginning on the date of the enactment 

6 of this Act, the Secretary of Health and Human Services 

7 (referred to in this Act as the ‘‘Secretary’’), acting 

8 through the Commissioner of Food and Drugs, shall with9 draw the approval under section 505 of the Federal Food, 

10 Drug, and Cosmetic Act of each application for a drug 

11 that contains isotretinoin as an active ingredient (includ12 ing the drug marketed as Accutane). During or after such 

13 period, any holder of an application that is subject to the 

14 preceding sentence may file with the Secretary a supple15 mental application for such drug, and the Secretary may 

16 approve the supplemental application in accordance with 

17 subsection (b). 

18 (b) RESTRICTIONS.—Any approval by the Secretary 

19 of a supplemental application for a drug containing 

20 isotretinoin pursuant to subsection (a) shall provide that 

21 such drug is being approved as a drug subject to subpart 

22 H of part 314 of title 21, Code of Federal Regulations. 

23 The Secretary shall under such subpart H establish re24 strictions on the distribution of the drug. Such restrictions 

25 shall require that distribution of the drug under all the 

26 approved supplemental applications be exclusively through 
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1 a single program, approved by the Secretary, that provides 

2 for the distribution of the drug in accordance with the fol3 lowing conditions: 

4 (1) Distribution of the drug by manufacturers 

5 is directly to pharmacists (without the involvement 

6 of entities engaged in the wholesale distribution of 

7 drugs), and each pharmacist receiving the drug is in 

8 compliance with the following: 

9 (A) The pharmacist has registered with the 

10 program. 

11 (B) The pharmacist has received education 

12 on potential side effects of the drug relating to 

13 birth defects and mental health or behavioral 

14 issues that, as of the day before the date of the 

15 enactment of this Act, were described on the 

16 approved labeling for the drug (including de17 pression, suicidal ideation, suicide attempts, 

18 suicide, and aggressive or violent behavior). 

19 (C) The pharmacist agrees that the drug 

20 will be dispensed only pursuant to prescriptions 

21 issued by practitioners at treatment centers cer22 tified under paragraph (2). 

23 (D) The pharmacist has signed and filed 

24 with the program a statement that the phar25 macist understands the conditions for participa-
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1 tion in the program as a pharmacist, and will 

2 maintain compliance with the agreement de3 scribed in subparagraph (C) and otherwise com4 ply with applicable conditions. 

5 (2) The program certifies clinics and medical 

6 offices as treatment centers regarding the drug, 

7 makes the certifications in accordance with the con8 ditions described in subsection (c), provides that the 

9 certifications are effective for one year, and main10 tains a registry of treatment centers for which cer11 tifications are in effect. 

12 (3) The program develops and makes available 

13 to practitioners materials for educating patients on 

14 the drug, including managing the risks associated 

15 with the drug, and such materials include a ques16 tionnaire, to be completed monthly by patients, that 

17 warns patients of the adverse side effects described 

18 in paragraph (1)(B) and monitors for the develop19 ment of any such effects in patients. 

20 (4) The drug is prescribed for a patient by a 

21 practitioner only in accordance with the following: 

22 (A) The drug is prescribed for severe, re23 calcitrant nodular acne that is unresponsive to 

24 conventional therapy, including antibiotics. 
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1 (B) The patient is registered with the pro2 gram. 

3 (C) Using the materials referred to in 

4 paragraph (3), the practitioner educates the pa5 tient on the drug, including providing one-on6 one, in-person counseling. 

7 (D) The practitioner provides to the pa8 tient the questionnaire referred to in paragraph 

9 (3), and the patient completes the question10 naire. 

11 (E) The patient signs a statement pro12 viding the informed consent of the patient to 

13 undergo treatment with the drug (or a parent 

14 or guardian of the patient signs the statement, 

15 in the case of a patient who is a minor or other16 wise lacks legal capacity). 

17 (F) The patient undergoes the appropriate 

18 blood tests. 

19 (G) In the case of a female patient—

20 (i) the education under subparagraph 

21 (C) includes education on the need to avoid 

22 becoming pregnant while being treated 

23 with the drug; and 

24 (ii) the practitioner determines that 

25 the patient is not pregnant, as indicated by 
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1 an electronic verification, provided to the 

2 practitioner by an accredited laboratory, 

3 that the patient has undergone a preg4 nancy test and received a negative result. 

5 (H) In the case of a male patient, the edu6 cation under subparagraph (C) includes edu7 cation on the need to avoid impregnating 

8 women while being treated with the drug. 

9 (I) The prescription is issued only after 

10 compliance with subparagraphs (B) through 

11 (H). 

12 (J) The prescription is for a 30-day supply 

13 of the drug, with no refills. 

14 (K) Each further prescription for the drug 

15 is issued by the practitioner to the patient only 

16 pursuant to another in-person consultation with 

17 the practitioner, and prior to issuing the pre18 scription, compliance with subparagraphs (C) 

19 through (I) is repeated. 

20 (L) The patient undergoes the appropriate 

21 blood tests 30 days after the conclusion of 

22 treatment with the drug. 

23 (5) Such additional conditions as the Secretary 

24 may by regulation determine to be necessary to pro25 tect the public health with respect to the drug. 
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1 (c) CERTIFICATION OF TREATMENT CENTERS.—For 

2 purposes of subsection (b)(2), the conditions for the pro3 gram to certify a clinic or medical office as a treatment 

4 center regarding a drug containing isotretinoin are as fol5 lows: 

6 (1) The program determines that each of the 

7 practitioners at the clinic or office who will prescribe 

8 the drug is in compliance with the following: 

9 (A) The practitioner is authorized under 

10 the law of the State involved to administer pre11 scription drugs. 

12 (B) The practitioner has registered with 

13 the program and received education on the po14 tential side effects referred to in subsection 

15 (b)(1)(B). 

16 (C) The practitioner agrees as follows: 

17 (i) The practitioner will prescribe the 

18 drug for a patient in accordance with sub19 section (b)(4). 

20 (ii) If a female patient being treated 

21 with the drug becomes pregnant, the prac22 titioner will immediately report the preg23 nancy to the program and provide follow24 up in accordance with the program. 
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1 (iii) The practitioner will not issue 

2 prescriptions for the drug by telephone or 

3 facsimile transmission, or through the 

4 Internet. 

5 (iv) The practitioner will—

6 (I) report to the Secretary any 

7 information received by the practi8 tioner on adverse events that are asso9 ciated with the use of the drug by pa10 tients of the practitioner; and 

11 (II) submit such reports quar12 terly, except in the case of a patient 

13 death associated with the drug, in 

14 which case the report will be sub15 mitted immediately, but in no case 

16 later than 15 days after the date on 

17 which the practitioner learns of the 

18 death. 

19 (D) The practitioner has signed and filed 

20 with the program a statement that the practi21 tioner understands the conditions for participa22 tion in the program as a practitioner, and will 

23 maintain compliance with the agreements de24 scribed in subparagraph (C) and otherwise com25 ply with applicable conditions. 
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1 (2) After the initial certification of the clinic or 

2 office, the program renews a certification for addi3 tional-one year periods only if the program has con4 ducted an evaluation to determine whether, during 

5 the preceding one-year period, each practitioner at 

6 the center who prescribes the drug has maintained 

7 substantial compliance with applicable conditions of 

8 the program. 

9 (3) Such additional conditions as the Secretary 

10 may by regulation determine to be necessary to pro11 tect the public health with respect to the drug. 

12 (d) MONITORING BY SECRETARY.—The Secretary 

13 shall monitor the distribution of drugs containing 

14 isotretinoin under supplemental applications approved 

15 under subsection (b), including the prescribing and dis16 pensing of the drug, to determine whether the drug is 

17 being distributed in accordance with the program ap18 proved by the Secretary under such subsection. 

19 SEC. 3. REPORTING OF ADVERSE EVENTS BY MANUFAC20 TURERS AND DISTRIBUTORS. 

21 (a) IN GENERAL.—Each person who is a manufac22 turer or distributor of a drug containing isotretinoin shall 

23 report to the Secretary any information received by such 

24 person on adverse events that are associated with such 

25 drug. In any case in which an individual reports an ad-
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1 verse event to such person and states that the individual 

2 believes the drug is a factor in the event, the person shall 

3 consider the event to be associated with the drug for pur4 poses of the preceding sentence. 

5 (b) TIMEFRAME FOR REPORTING.—A person de6 scribed in subsection (a) shall submit reports under such 

7 subsection to the Secretary on a quarterly basis, except 

8 that in the case of a death associated with isotretinoin, 

9 the report shall be submitted immediately, but in no case 

10 later than 15 days after the date on which the person 

11 learns of the death. 

12 SEC. 4. FURTHER STUDIES. 

13 (a) IN GENERAL.—The Secretary, in consultation 

14 with the Director of the Centers for Disease Control and 

15 Prevention, the Director of the National Institutes of 

16 Health, and the Director of the National Institute of Men17 tal Health, shall continue to conduct and support appro18 priate studies to explore, in adolescents and adults—

19 (1) the effects of isotretinoin and retinoid acid 

20 on the central nervous system, including the brain; 

21 and 

22 (2) the behavioral effects of isotretinoin, includ23 ing depression, suicidal ideation, suicide attempts, 

24 suicide, and aggressive or violent behavior. 
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1 (b) AUTHORIZATION OF APPROPRIATIONS.—For the 

2 purpose of studies under subsection (a), there are author3 ized to be appropriated such sums as may be necessary 

4 for fiscal year 2005 and each subsequent fiscal year, in 

5 addition to any other authorizations of appropriations that 

6 are available for such purpose.

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