Federal Register / Vol. 68, No. 71 / Monday, April 14, 2003 / Notices 17953 CFR Number of Responses per Avg burden per Total annual reference Data collection respondents respondent response (in hrs.) burden (in hrs.) 73.6 (c–e) Request for exemption .............................. 17 1 70/60 20 73.14 ........ Transfer of select agent ............................ 1,000 5 1.75 8,750 73.6 (a)(2) Clinical and diagnostic laboratory exemp- 1,000 4 1 4,000 tion report. 73.7(i) ....... Notification of inactivation .......................... 6 1 30/60 3 73.8(g) ..... Request expedited review ......................... 6 1 30/60 3 73.10(b) ... Documentation of self-inspection .............. 1,000 1 1 1,000 73.13(f) .... Documentation of training ......................... 1,000 1 2 8,700 73.18 ........ Administrative review ................................. 14 1 4 56 73.15(d) ... Ensure secure recordkeeping system ....... 1,000 1 30/60 4,000 Total .. .................................................................... 1,000 ................................ ................................ 34,804 Dated: April 7, 2003. and other comments should be patients not improved by estrogen Thomas Bartenfeld, identified with Docket No. 76N–0377 alone.’’ Acting Associate Director for Policy, Planning and submitted to the Dockets In the Federal Register of December and Evaluation, Centers for Disease Control Management Branch (HFA–305), Food 17, 1998 (63 FR 69631), FDA withdrew and Prevention. and Drug Administration, 5630 Fishers approval of estrogen-containing drugs [FR Doc. 03–9019 Filed 4–11–03; 8:45 am] Lane, rm. 1061, Rockville, MD 20852. A insofar as they are indicated for BILLING CODE 4163–18–P request for an opinion on the postpartum breast engorgement because applicability of this notice to a specific estrogens have not been shown to be drug product should be directed to the safe for this use. That Federal Register DEPARTMENT OF HEALTH AND Division of New Drugs and Labeling notice included, among others, four of HUMAN SERVICES Compliance (HFD–310), Center for Drug the five NDAs listed above. (NDA 11– Evaluation and Research, Food and 267 was not included because the drug Food and Drug Administration Drug Administration, 5600 Fishers product covered by that application, [Docket Nos. 78N–0377 and 98P–1041; DESI Lane, Rockville, MD 20857. Halodrin Tablets, was not labeled for 7661] use for postpartum breast engorgement.) FOR FURTHER INFORMATION CONTACT: Given this December 17, 1998 notice, David T. Read, Center for Drug Certain Estrogen-Androgen the following discussion relates only to Evaluation and Research (HFD–7), Food Combination Drugs; Drugs for Human the second indication found safe and Use; Drug Efficacy Study and Drug Administration, 5600 Fishers effective in the 1972 notice, i.e., ‘‘for the Implementation; Amendment and Lane, Rockville, MD 20857, 301–594– menopausal syndrome in patients not Opportunity for Hearing 2041. improved by estrogen alone.’’ SUPPLEMENTARY INFORMATION: In the Federal Register of September AGENCY: Food and Drug Administration, 29, 1976 (41 FR 43112), the agency HHS. I. Background announced that the menopausal ACTION: Notice. In a notice published in the Federal indication for combination drugs SUMMARY: The Food and Drug Register of September 8, 1972 (37 FR containing an estrogen and an androgen Administration (FDA) is amending a 18225), FDA announced its evaluation was revised to read as follows: previous Federal Register notice to of the various indications claimed for Moderate to severe vasomotor symptoms the following combination drugs that associated with the menopause in those reclassify certain estrogen-androgen patients not improved by estrogen alone. combination drugs as lacking contain an estrogen and an androgen: (There is no evidence that estrogens are substantial evidence of effectiveness for 1. Halodrin Tablets (NDA 11–267), effective for nervous symptoms or depression the treatment of moderate to severe containing fluoxymesterone and ethinyl which might occur during menopause, and vasomotor symptoms associated with estradiol; they should not be used to treat these the menopause in those patients not 2. Tylosterone Injection (NDA 8–099), conditions.) 41 FR 43112 at 43113. (emphasis improved by estrogen alone. The agency containing diethylstilbestrol and in original) This action was taken as one part of is taking this action because for this methyltestosterone; a large agency undertaking with respect indication there is not substantial 3. Tylosterone Tablets (NDA 7–661), to the labeling (patient-directed as well evidence of the contribution of each containing diethylstilbestrol and as physician-directed) for all estrogen- component to the effectiveness of these methyltestosterone; containing drug products. The following combination drugs. FDA is offering an 4. Tace with Androgen Capsules documents were also published in the opportunity for a hearing to persons (NDA 10–597), containing Federal Register of September 29, 1976: affected by this action. chlorotrianisene and (1) 41 FR 43110 (DESI 2238; Certain DATES: Requests for hearings are due on methyltestosterone; Preparations for Vaginal Use); (2) 41 FR or before May 14, 2003. Data in support 5. Deladumone Injection and 43114 (DESI 1543; Certain Estrogen- of hearing requests are due June 13, Deladumone OB Injection (NDA 9–545), Containing Drugs for Oral or Parenteral 2003. containing testosterone enanthate and Use); (3) 41 FR 43117 (DESI 740, 1543, ADDRESSES: Communications in estradiol valerate. 2238, and 7661; Physician Labeling and response to this notice should be As announced in that 1972 notice, Patient Labeling for Estrogens for identified with the reference number FDA found these drugs to be safe and General Use); and (4) 41 FR 43108 (a DESI 7661 and directed to the attention effective for the ‘‘prevention of proposed rule that would require certain of the appropriate office named below. postpartum breast engorgement and ‘‘for patient-directed labeling for estrogens A request for hearing, supporting data, the menopausal syndrome in those for general use). VerDate Jan<31>2003 14:06 Apr 11, 2003 Jkt 200001 PO 00000 Frm 00048 Fmt 4703 Sfmt 4703 E:\FR\FM\14APN1.SGM 14APN1 17954 Federal Register / Vol. 68, No. 71 / Monday, April 14, 2003 / Notices The five applications listed below (59 FR 9989), respectively. The agency improved by estrogen alone. The use of were approved on the basis of the 1976 withdrew approval of NDA 7–661 these combination drug products for any notice, and their approvals are (Tylosterone Tablets) and NDA 8–099 other use, including but not limited to withdrawn in a notice published (Tylosterone Injection), both containing the treatment of other menopausal elsewhere in today’s issue of the diethylstilbestrol and symptoms, will not be considered in Federal Register: methyltestosterone, and NDA 9–545 this proceeding. The effectiveness of 1. NDA 17–968 and ANDA 85–603 (Deladumone OB Injection and estrogen-androgen combination (testosterone cypionate 50 milligrams/ Deladumone Injection, each containing products for indications not covered by milliliter (mg/mL) and estradiol testosterone enanthate and estradiol this proceeding should be addressed cypionate 2 mg/mL injection). valerate) in a notice published in the through the new drug application 2. ANDA 85–860 and ANDA 86–423 Federal Register of October 29, 1998 (63 process. (testosterone enanthate 180 mg/mL and FR 58053). estradiol valerate 8 mg/mL injection). In response to the notice of October II. The Safety and Effectiveness of 3. ANDA 85–865 (testosterone 29, 1998, on November 24, 1998, Solvay Estrogen-Androgen Combination Drug enanthate 90 mg/mL and estradiol Pharmaceuticals submitted a citizen Products for the Treatment of valerate 4 mg/mL injection). petition (Docket No. 98P–1041) Vasomotor Symptoms Associated With In 1981, the Center for Drug requesting that FDA determine that the Menopause in Patients Not Improved Evaluation and Research (CDER) (then products covered by the three by Estrogen Alone the Bureau of Drugs) determined in applications withdrawn in the October The agency took a renewed interest in response to requests from the sponsors 21, 1998, notice were not withdrawn for estrogen-androgen combination drug that the effectiveness finding of the 1976 reasons of safety or effectiveness. As products when concerns were raised DESI 7661 Federal Register notice could FDA is doing for the five estrogen- about the effect of androgens in be applied to two combination drug androgen combination products whose lowering high-density lipoproteins products that were not listed in the 1976 approvals are being withdrawn in a (Refs. notice, but were being marketed at the notice published elsewhere in today’s 1 and 2). It is believed that oral time: (1) Conjugated estrogens and issue of the Federal Register, the agency androgens can reverse the favorable methyltestosterone and (2) esterified is deferring to the outcome of this impact of estrogen on lipoproteins (Ref. estrogens and methyltestosterone. Based proceeding to amend the 1976 notice 3). Other safety concerns were on this finding, FDA filed (i.e., accepted the determination of whether the for review) abbreviated new drug virilization (Refs. 4 and 5) and possible products covered by the three liver toxicity (Refs. 6, 7, and 8). applications (ANDAs) for these drug applications named in Solvay’s petition products. Wyeth-Ayerst submitted FDA concluded that the negative were withdrawn for reasons of safety or effects