I 

109TH CONGRESS 

1ST SESSION H. R. 2956 

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, 2005 

Mr. STUPAK 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’’. 

6 SEC. 2. FEDERAL FOOD, DRUG, AND COSMETIC ACT; RE7 STRICTIONS REGARDING DRUG 

8 ISOTRETINOIN. 

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

10 the 30-day period beginning on the date of the enactment 
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1 of this Act, the Secretary of Health and Human Services 

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

3 through the Commissioner of Food and Drugs, shall with4 draw the approval under section 505 of the Federal Food, 

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

6 that contains isotretinoin as an active ingredient (includ7 ing the drug marketed as Accutane). During or after such 

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

9 preceding sentence may file with the Secretary a supple10 mental application for such drug, and the Secretary may 

11 approve the supplemental application in accordance with 

12 subsection (b). 

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

14 of a supplemental application for a drug containing 

15 isotretinoin pursuant to subsection (a) shall provide that 

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

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

18 The Secretary shall under such subpart H establish re19 strictions on the distribution of the drug. Such restrictions 

20 shall require that distribution of the drug under all the 

21 approved supplemental applications be exclusively through 

22 a single program, approved by the Secretary, that provides 

23 for the distribution of the drug in accordance with the fol24 lowing conditions: 
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1 (1) Distribution of the drug by manufacturers 

2 is directly to pharmacists (without the involvement 

3 of entities engaged in the wholesale distribution of 

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

5 compliance with the following: 

6 (A) The pharmacist has registered with the 

7 program. 

8 (B) The pharmacist has received education 

9 on potential side effects of the drug relating to 

10 birth defects and mental health or behavioral 

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

12 enactment of this Act, were described on the 

13 approved labeling for the drug (including de14 pression, suicidal ideation, suicide attempts, 

15 suicide, and aggressive or violent behavior). 

16 (C) The pharmacist agrees that the drug 

17 will be dispensed only pursuant to prescriptions 

18 issued by practitioners at treatment centers cer19 tified under paragraph (2). 

20 (D) The pharmacist has signed and filed 

21 with the program a statement that the phar22 macist understands the conditions for participa23 tion in the program as a pharmacist, and will 

24 maintain compliance with the agreement de-
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1 scribed in subparagraph (C) and otherwise com2 ply with applicable conditions. 

3 (2) The program certifies clinics and medical 

4 offices as treatment centers regarding the drug, 

5 makes the certifications in accordance with the con6 ditions described in subsection (c), provides that the 

7 certifications are effective for one year, and main8 tains a registry of treatment centers for which cer9 tifications are in effect. 

10 (3) The program develops and makes available 

11 to practitioners materials for educating patients on 

12 the drug, including managing the risks associated 

13 with the drug, and such materials include a ques14 tionnaire, to be completed monthly by patients, that 

15 warns patients of the adverse side effects described 

16 in paragraph (1)(B) and monitors for the develop17 ment of any such effects in patients. 

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

19 practitioner only in accordance with the following: 

20 (A) The drug is prescribed for severe, re21 calcitrant nodular acne that is unresponsive to 

22 conventional therapy, including antibiotics. 

23 (B) The patient is registered with the pro24 gram. 
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1 (C) Using the materials referred to in 

2 paragraph (3), the practitioner educates the pa3 tient on the drug, including providing one-on4 one, in-person counseling. 

5 (D) The practitioner provides to the pa6 tient the questionnaire referred to in paragraph 

7 (3), and the patient completes the question8 naire. 

9 (E) The patient signs a statement pro10 viding the informed consent of the patient to 

11 undergo treatment with the drug (or a parent 

12 or guardian of the patient signs the statement, 

13 in the case of a patient who is a minor or other14 wise lacks legal capacity). 

15 (F) The patient undergoes the appropriate 

16 blood tests. 

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

18 (i) the education under subparagraph 

19 (C) includes education on the need to avoid 

20 becoming pregnant while being treated 

21 with the drug; and 

22 (ii) the practitioner determines that 

23 the patient is not pregnant, as indicated by 

24 an electronic verification, provided to the 

25 practitioner by an accredited laboratory, 
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1 that the patient has undergone a preg2 nancy test and received a negative result. 

3 (H) In the case of a male patient, the edu4 cation under subparagraph (C) includes edu5 cation on the need to avoid impregnating 

6 women while being treated with the drug. 

7 (I) The prescription is issued only after 

8 compliance with subparagraphs (B) through 

9 (H). 

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

11 of the drug, with no refills. 

12 (K) Each further prescription for the drug 

13 is issued by the practitioner to the patient only 

14 pursuant to another in-person consultation with 

15 the practitioner, and prior to issuing the pre16 scription, compliance with subparagraphs (C) 

17 through (I) is repeated. 

18 (L) The patient undergoes the appropriate 

19 blood tests 30 days after the conclusion of 

20 treatment with the drug. 

21 (5) Such additional conditions as the Secretary 

22 may by regulation determine to be necessary to pro23 tect the public health with respect to the drug. 

24 (c) CERTIFICATION OF TREATMENT CENTERS.—For 

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

2 center regarding a drug containing isotretinoin are as fol3 lows: 

4 (1) The program determines that each of the 

5 practitioners at the clinic or office who will prescribe 

6 the drug is in compliance with the following: 

7 (A) The practitioner is authorized under 

8 the law of the State involved to administer pre9 scription drugs. 

10 (B) The practitioner has registered with 

11 the program and received education on the po12 tential side effects referred to in subsection 

13 (b)(1)(B). 

14 (C) The practitioner agrees as follows: 

15 (i) The practitioner will prescribe the 

16 drug for a patient in accordance with sub17 section (b)(4). 

18 (ii) If a female patient being treated 

19 with the drug becomes pregnant, the prac20 titioner will immediately report the preg21 nancy to the program and provide follow22 up in accordance with the program. 

23 (iii) The practitioner will not issue 

24 prescriptions for the drug by telephone or 
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1 facsimile transmission, or through the 

2 Internet. 

3 (iv) The practitioner will— 

4 (I) report to the Secretary any 

5 information received by the practi6 tioner on adverse events that are asso7 ciated with the use of the drug by pa8 tients of the practitioner; and 

9 (II) submit such reports quar10 terly, except in the case of a patient 

11 death associated with the drug, in 

12 which case the report will be sub13 mitted immediately, but in no case 

14 later than 15 days after the date on 

15 which the practitioner learns of the 

16 death. 

17 (D) The practitioner has signed and filed 

18 with the program a statement that the practi19 tioner understands the conditions for participa20 tion in the program as a practitioner, and will 

21 maintain compliance with the agreements de22 scribed in subparagraph (C) and otherwise com23 ply with applicable conditions. 

24 (2) After the initial certification of the clinic or 

25 office, the program renews a certification for addi-
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1 tional one-year periods only if the program has con2 ducted an evaluation to determine whether, during 

3 the preceding one-year period, each practitioner at 

4 the center who prescribes the drug has maintained 

5 substantial compliance with applicable conditions of 

6 the program. 

7 (3) Such additional conditions as the Secretary 

8 may by regulation determine to be necessary to pro9 tect the public health with respect to the drug. 

10 (d) MONITORING BY SECRETARY.—The Secretary 

11 shall monitor the distribution of drugs containing 

12 isotretinoin under supplemental applications approved 

13 under subsection (b), including the prescribing and dis14 pensing of the drug, to determine whether the drug is 

15 being distributed in accordance with the program ap16 proved by the Secretary under such subsection. 

17 (e) ADDITIONAL APPROVED USES.— 

18 (1) IN GENERAL.—With respect to a drug that 

19 contains isotretinoin as an active ingredient, this 

20 section may not be construed as prohibiting the Sec21 retary from approving an application under section 

22 505 of the Federal Food, Drug, and Cosmetic Act 

23 for such a drug for a use different than the use de24 scribed in subsection (b)(4)(A) (which different use 

25 is referred to in this subsection as a ‘‘new use’’). 
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1 (2) CONDITIONS.—For purposes of paragraph 

2 (1): 

3 (A) An approval by the Secretary of a new 

4 use is subject to the same conditions as apply 

5 under subsection (b) with respect to the use de6 scribed in paragraph (4)(A) of such subsection. 

7 (B) In applying such conditions to the new 

8 use, the Secretary may authorize the program 

9 under subsection (b) to be expanded to include 

10 the new use, or the Secretary may require the 

11 establishment of a separate program for the 

12 new use. 

13 (C) The requirement of monitoring under 

14 subsection (d) applies with respect to the new 

15 use to the same extent and in the same manner 

16 as the requirement applies with respect to the 

17 use described in subsection (b)(4)(A). 

18 (D) Section 3 applies with respect to the 

19 new use. 

20 SEC. 3. REPORTING OF ADVERSE EVENTS BY MANUFAC21 TURERS AND DISTRIBUTORS. 

22 (a) IN GENERAL.—Each person who is a manufac23 turer or distributor of a drug containing isotretinoin shall 

24 report to the Secretary any information received by such 

25 person on adverse events that are associated with such 
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1 drug. In any case in which an individual reports an ad2 verse event to such person and states that the individual 

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

4 consider the event to be associated with the drug for pur5 poses of the preceding sentence. 

6 (b) TIMEFRAME FOR REPORTING.—A person de7 scribed in subsection (a) shall submit reports under such 

8 subsection to the Secretary on a quarterly basis, except 

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

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

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

12 learns of the death. 

13 SEC. 4. FURTHER STUDIES. 

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

15 with the Director of the Centers for Disease Control and 

16 Prevention, the Director of the National Institutes of 

17 Health, and the Director of the National Institute of Men18 tal Health, shall continue to conduct and support appro19 priate studies to explore, in adolescents and adults— 

20 (1) the effects of isotretinoin and retinoid acid 

21 on the central nervous system, including the brain; 

22 and 

23 (2) the behavioral effects of isotretinoin, includ24 ing depression, suicidal ideation, suicide attempts, 

25 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 2006 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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