Unknown

listed under "unknown," it is because the patient failed to note the information in her correspondence or the clinician did not note the information on the inquiry form.

Side Reactions

Table 3 shows the incidence of side effects following administration of diethylstilbestrol. Usually, no reaction was noted before a lapse of at least six hours after ingestion of the first pill. Enteric coated diethylstilbestrol only delayed the onset of reaction but did not prevent it. No serious side effect was known in any of the 1,000 cases while taking diethylstilbestrol or afterward. It will be noted that 45.2% had virtually no side reactions. In some cases, patients observed more than one side effect.

Patients having headaches were carefully questioned. The headaches varied in location from frontal to generalized and most were dull. Only one girl had a vascular headache by histom and sha was known on bara a

past mistory of Bigtailie. Ine charac ter of the following menses varied

from the usual, as noted in Table i

The mechanism of action appeas to be on the endometrial implantace site, though other actions such as increase in speed of ovum transpor through the genital tract, have been noted in animal observations. There are many animal studies in the liter ature concerning this subject, and a few additional references are listed

References

1. Tietze C: Problems of pregnancy resulting from a single unprotected coitus. Fertil Ster 11:485-483, 1950.

2. Morris JM. Van Wagenen G: Compend Amer J Obstet Gynec 96:54, 1965.

3. Heckel GP. Allen WM: Maintenance of m pus luteum and inhibition of partantes in bits by injection of estrogenic normone. Eno nology 24:137, 1939.

4. Courrier R, Raynaud R: Etude quantra SER de l'avortement folliculinique provoque coxt a lapine par l'hormone cristalisee: Realization o un avortement partiel Compt Band Sor Zi 116:1073, 1934..

5. Nutting EF. Saunders FJ: Postropulat effect of two antifertility agents on ova 29 port and implantation Sue Exp End X-4 131:1326-1331, 1969.

6. Jacob D. Morris J: Estrogenic activity of postcoital antifertility compounds. Fertil Steri 20:211-222, 1959.

7. Emmens CW: Postcoital contraception. Ent Med Bull 26:45-51, 1970.

National Bureau of Standards EXPANDED VINYL FABRICS FOR APPAREL USE

Withdrawal of Commercial Standard

In accordance with § 10.12 of the Department's "Procedures for the Development of Voluntary Product Standards" (15 CFR Part 10, as revised: 35 FR 8349 dated May 28, 1970), notice is hereby given of the withdrawal of Commercial Standard CS 258-63, "Expanded Vinyl Fabrics for Apparel Use."

This action is taken in furtherance of the Department's announced intentions as set forth in the public notice appearing in the FEDERAL REGISTER of July 2, 1973 (38 FR 17520), to withdraw this standard.

The effective date for the withdrawal of this standard will be November 26, 1973. This withdrawal action terminates the authority to refer to this standard as a voluntary standard developed under the Department of Commerce Procedures.

Dated September 19, 1973.

RICHARD W. ROBERTS,
Director.

[FR Doc.73-20475 Filed 9-25-73:8:45 am]

DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE Food and Drug Administration (DESI 740; Docket No. FDC-D-664; NQA 4-038, etc.]

CERTAIN ESTROGENS FOR ORAL OR PARENTERAL USE

Drogs for Human Use, Drug Efficacy Study Implementation; Follow-Up Notice

In a notice published in the FEDERAL

REGISTER of November 10, 1971 (36 FR 21537), the Commissioner of Foods and Drugs announced his conclusions pursuant to evaluation of reports received from the National Academy of SciencesNational Research Council, Drug Efficacy Study Group on the following drugs:

1. Preparations containing dienestrol.

a. Restrol tablets: The Central Pharmacal Co., 116-128 East Third Street, Seymour, IN 47274 (NDA 6-428). (Two reports.)

b. Synestrol tablets; White Laboratories, Inc., Kenilworth, N.J. 07033 (NDA 5-991).

2. Preparations containing diethylstilbestrol. a. Diethylstilbestrol Enseals and Tablets; Eli Lilly and Co., Post Office Box 818. Indianapolis, IN 46204 (NDA 4-039 and 4-041 (previously stated to be 4 040). (Three reports.)

4-297).

e. Stilbestrol tablets; High Chemical Co., 1760 North Howard Street, Philadelphia, PA 19122 (NDA 5-233).

1. Stilbetin tablets and enteric coated tablets; E. R. Squibb and Sons, Inc. Georges Road, New Brunswick, N.J. 08903 (NDA 4-056).

g. Diethylstilbestrol Perles; The Upjohn Co., 7171 Portage Road, Kalamazoo, MI 49002 (NDA 4-073).

h. Diethylstilbestrol in oil injections: Eli Lilly and Co. (NDA 4-038 (previously stated to be 1-221)).

1 Diethylstilbestrol in ethyl oleate injection; Eli Lilly and Co. (NDA 7-844). 3. Preparations containing other diethylstilbestrol derivatives. a. D.S.D. tabdiethylstilbestrol dipropionate: The Blue lets and enteric coated tables, containing Line Chemical Co., 302 South Broadway. St. Louis, MO 63102 (NDA 5-159).

b. Stilphostrol ampoules and tableta, diphics. containing diethylstilbestrol

phate; Dome Laboratories, Divine Miles Laboratories. Inc., 400 Mc Lane, West Haven, CT 06316 0.5%

10-010).

4. Preparation containing promethestrol dipropionate. a. Mebrane Debrapionate tablets; Reed and Carrick Pharmaceuticals, 30 Boright Atende Kenilworth, N.J. 07033 (NDA 6-012).

The notice stated that these drugs were regarded as effective, probably elfective, possibly effective, and lacking substantial evidence of effectiveness for their various indications.

No data were submitted in sumport af any of the less than effective Indications and the drugs are now regarded to either lack substantial evidence of effectivenes or are not shown to be safe for those indications.

Accordingly, with respect to these products, the revised effectiveness clas sification and marketing status are as follows: classification The

A. Effectiveness Food and Drug Administration has considered the Academy's reports, as well as other available evidence, and concludes that, except for oral dosage forms containing 25 milligrams or more of diethylstilbestrol per tablet and parenteral dosage forms containing 25 milligram or more of diethylstilbestrol per millliter, the drugs are effective for those indications described as effective in the notice of November 10, 1971. Dosage forms containing 25 milligrams or more of diethylstilbestrol per tablet or r liter are either regarded as contra cated or inappropriate dosages for the indications claimed in the labeling and raise a question of safety. Appearing elsewhere in this issue of the Fores hearing on the proposal to withdraw ap REGISTER is a notice of opportunity for proval of those parts of new drug applcations providing for such dosage form strengths.

The drugs lack substantial evidence of effectiveness for all of their other labeled indications.

B. Conditions for approval and marketing. The Food and Drug Administration is prepared to approve abbreviated new drug applications and abbreviated supplements to previously approved new drug applications under the conditions

described herein.

1. Form of drug. These preparations are in tablet, enteric coated tablet, or

capsule form suitable for oral administration; or are sterile preparations in a form suitable for parenteral administra

tion.

2. Labeling conditions. The labeling conditions are the same as those described in the notice of November 10. 1971, except that the probably efective and possibly effective indications are no longer, allowable. Complete labeling guidelines are available upon request.

3. Marketing status. Marketing of such drugs may be continued under the condtions described in the notice entr "Conditions for Marketing New D Evaluated in Drug Efficacy Study." puplished in the FEDERAL REGISTER July 14. 1970 (35 FR 11273), as follows:

a. For holders of "deemed approved" new drug applications (ie., an application which became effective on the basts

of safety prior to October 10, 1962), the submission of a supplement for revised labeling and an abbreviated supplement for updating information as described in paragraphs (a) (1) (i) and (iii) of the notice of July 14, 1970.

b. For any person who does not hold an approved or effective new drug application, the submission of an abbreviated new drug application as described in paragraph (a) (3) (i) of that notice.

c. For any distributor of the drug, the use of labeling in accord with this announcement for any such drug shipped within the jurisdiction of the Act as described in paragraph (b) of that notice.

C. Notice of opportunity for a hearing. Notice is given to the holder's) of the new drug application (s) and to any other interested person that the Commissioner proposes to issue an order under section 505(e) of the Federal Food, Drug, and Cosmetic Act (21 US.C. 355(e)) withdrawing approval of the listed new drug application (s) and all amendments and supplements thereto providing for indications lacking substantial evidence of effectiveness referred to in paragraph A of this notice on the grounds that new information before him with respect to the drug (s), evaluated together with the evidence available to him at the time of approval of the application(s), shows there is a lack of substantial evidence that the drug (s) will have all the effects purported or represented to have under the conditions of use prescribed, recommended, or suggested in the labeling. An order withdrawing approval will not issue wit' respect to any application (s) supplemented, in accord with this notice, to delete the claim (s) lacking substantial evidence of effectiveness.

Any manufacturer or distributor of such an identical, related, or similar product is an interested person who may in response to this notice submit data and information, request that the new drug application (s) not be withdrawn, request hearing, and participate as a party in any hearing.

In accordance with the provisions of section 505 of the Act (21 U.S.C. 355)

and the regulations promulgated thereunder (21 CFR Part 130), the Commis

sioner hereby gives the applicant(s) and any other interested person an opportunity for a hearing to show why approval of the new drug application(s) providing for the claim (s) involved should not be withdrawn.

On or before October 26, 1973, the applicant(s) and any other interested person may file with the Hearing Clerk, Food and Drug Administration, Room 6-86, 5600 Fishers Lane, Rockville, Maryland 20852, a written appearance electing whether or not to avail himself of the opportunity for a hearing. Failure of an applicant or any other interested person to file a written appearance of election within the specified time will constitute an election by him not to avail himself of the opportunity for a hearing. No extension of time may be granted..

NOTICES

26825

Supplements (identify with NDA number): Office of Scientific Evaluation (BD-100', Bureau of Drugs.

(Identify as such): Generic Drug Staff (BD-69), Office of Scientific Evaluation, Bureau of Drugs.

If an applicant or any other interested person elects to avail himself of the opportunity for a hearing. he must file, on or before October 26, 1973, a written appearance requesting the hearing, giving the reasons why approval of the new drug application(s) should not be withdrawn, together with a well-organized and full-factual analysis of the clinical and other investigational data he is prepared to prove in support of his opposition. A request for a hearing may not rest upon mere allegations or denials, but must set forth specific acts showing that a genuine and substantial issue of fact requires a hearing (21 CFR 130.14(b)).

If review of the data submitted by an applicant or any other interested person warrants the conclusion that there exists substantial evidence demonstrating the effectiveness of the product(s) for the labeling claim (s) involved, the Commissioner will rescind this notice of opportunity for hearing.

If review of the data in the application(s) and data submitted by the applicant(s) or any other interested person in a request for a hearing, together with the reasoning and factual analysis in a request for a hearing, warrants the coclusion that no genuine and substantial issue of fact precludes the withdrawal of approval of the application(s), the Commissioner will enter an order making findings and conclusions on such data and withdrawing approval of application(s) not supplemented to delete the claim (s) involved.

If., upon the request of the new drug applicant(s) or any other interested person, a hearing is justified, the issues will be defined, a hearing examiner will be named, and he shall issue, as soon as practicable after October 26, 1973, a written notice of the time and place at which the hearing will commence. All persons interested in identical, related, or similar products covered by the new opportunity to appear at the hearing, file drug application(s) will be afforded an briefs, present evidence, cross-examine witnesses, submit suggested findings of fact, and otherwise participate as a party. The hearing contemplated by this notice will be open to the public except that any portion of the hearing that concerns a method or process the Commissioner finds entitled to protection as a trade secret will not be open to the public, unless the respondent specifies

otherwise in his appearance.

Communications forwarded in response to this notice should be identified with the reference number DESI 740, directed to the attention of the appropriate office listed below, and addressed to the Food and Drug Administration, 600 Fishers Lane, Rockville, MD 20852

Request for Hearing (identify with Docket number): Hearing Clerk (CC-20), Room 6-86. Parklawn Building.

Requests for Academy's report: Drug Efficacy Study Information Control (BD-66), Bureau of Drugs.

All other communications regarding this announcement: Drug Efficacy Study Implementation Project Manager (BD-101), Bureau of Drugs.

Received requests for a hearing may be seen in the Office of the Hearing Clerk (address given above) during regular business hours, Monday through Friday.

This notice is issued pursuant to provisions of the Federal Food, Drug, and Cosmetic Act (secs. 502, 505, 52 Stat. 1050-53, as amended; 21 U.S.C. 352, 355), and the Administrative Procedure Act (5 U.S.C. 554), and under the authority delegated to the Commissioner of Food and Drugs (21 CFR 2.120). Dated September 12, 1973.

A. M. SCHMIDT, Commissioner of Food and Drugs. [FR Doc.73-20442 Filed 9-21-73;8:45 am]

a notice (DESI 740 published in the FEDERAL REGISTER of November 10, 1971 (36 FR 21537), the Commissioner of Foods and Drugs announced his conclusions pursuant to evaluation of reports received from the National Academy of Sciences-National

Research Council, Drug Efficacy Study Group concerning certain orally and parenterally administered estrogens. Appearing elsewhere in this issue of the FEDERAL REGISTER is a followup notice describing the conditions under which certain of those products are regarded to be effective:

The following new drug applications referenced in the notice provide for oral dosage forms containing 25 mg. or more of diethylstilbestrol and a parenteral dosage form (1 ml. ampule) containing 25 mg. of diethylstilbestrol. Such large single dosages of diethylstilbestrol are regarded as either contraindicated (e.g.. for accidents of pregnancy), and/or are in excess of the amounts recognized as appropriate for the indications claimed in the labeling reviewed by the Academy.

thus raising a question of safety for use

for the indications claimed.

NDAS 4-039 and 4-041: Those parts of the NDA's providing for Diethylstilbestrol Tablets and Enseals containing 25 Post Office Box 618, Indianapolis, IN mg. diethylstilbestrol; Eli Lilly and Co., 46206.

NDA 6-603: Those parts of the NDA providing for a tablet containing 25 mg.

26826

diethylstilbestrol; Rexall Drug Company, 3901 North Kingshighway, St. Louis, MO 63115.

NDA 4-056: Those parts of the NDA providing for tablets containing 25 and 100 mg. diethylstilbestrol; E. R. Squibb and Sons, Lawrenceville-Princeton Road, Post Office Box 4000, Princeton, N.J. 08540.

NDA 7-844: Diethylstilbestrol Ampoules (1 ml.), containing 25 mg. diethylstilbestrol in ethyl oleate; Eli Lilly and Co. This dosage form had been labeled only for use in certain types of accidents of pregnancy. Lilly discontinued this product in 1966 and approval of the NDA was withdrawn February 8, 1972 (37 FR 2851), on grounds that the applicant had failed to make reports under section 505(j) of the Act (21 U.S.C. 355 (j)) and § 130.13 or § 130.35(e) and (f) of the new drug regulations (21 CFR 130.13 and 130.35). In view of that, this product is included in this notice only for the purpose of informing interested persons of the conclusions reached in the Drug Efficacy Study concerning

it.

Therefore, notice is given to the holder(s) of the new drug application(s) and to any other interested person that the Commissioner proposes to issue an order under section 505(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355

(e)) withdrawing approval of pertinent parts of the listed new drug application(s) and all amendments and supplements thereto on the grounds that new Information before him with respect to the drug(s), evaluated together with the evidence available to him at the time of approval of the application(s) shows that the drugs are not shown to be safe for use under the conditions of use prescribed, recommended, or suggested in the labeling.

All identical, related, or similar products, not the subject of an approved new drug application, are covered by the new drug application(s) reviewed. See 21 CFR 130.40 (37 F.R. 23185, October 31, 1972). Any manufacturer or distributor of such an identical, related, or similar product is an interested person who may in response to this notice submit data and information, request that the new drug application (s) not be withdrawn, request a hearing, and participate as a party in any hearing. Any person who wishes to determine whether a specific product is covered by this notice should write to the Food and Drug Administration, Bureau of Drugs, Office of Compliance (BD-300), 5600 Fishers Lane, Rockville, Maryland 20852.

In accordance with the provisions of section 505 of the Act (21 US.C. 355) and the regulations promulgated there under (21 CFR Part 130), the Commissioner hereby gives the applicant(s) and any other interested person an opportunity for a hearing to show why approval of the new drug application(s) should not be withdrawn.

On or before October 26, 1973, the applicant(s) and any other interested person is required to file with the Hearing

NOTICES

Clerk, Food and Drug Administration, Room 6-86, 5600 Fishers Lane, Rockville, Maryland 20852, a written appearance electing whether or not to avail himself of the opportunity for a hearing. Failure of an applicant or any other interested person to file a written appearance of election within the specified time will constitute an election by him not to avail himself of the opportunity for a hearing. No extension of time may be granted.

If no person elects to avail himself of the opportunity for a hearing, the Commissioner without further notice will enter a final order withdrawing approval of pertinent parts of the application(s).

If an applicant or any other interested person elects to avail himself of the opportunity for a hearing, he must file, on or before October 26, 1973, a written appearance requesting the hearing, giving the reasons why approval of the new drug application(s) should not be withdrawn, together with a well-organized and full-factual analysis of the clinical and other investigational data he is prepared to prove in support of his opposition. A request for a hearing may not rest upon mere allegations or denials, but must set forth specific facts showing that a genuine and substantial issue of fact requires a hearing (21 CFR 130.14

(b)).

(address given above) during regular business hours, Monday through Friday.

This notice is issued pursuant to provisions of the Federal Food. Drug, and Cosmetic Act (sec. 505, 52 Stat. 1052-33, as amended: 21 US.C. 355) and the Administrative Procedure Act (5 US.C. 554), and under authority delegated to the Commissioner (21 CFR 2.120). Dated September 12, 1973.

A. M. SCHMIDT. Commissioner of Food and Drugs. {FR Doc.73-20443 Piled 9-21-73:8.45 am

Office of Education NATIONAL ADVISORY COUNCIL ON

INDIAN EDUCATION

Notice of Meeting

Notice is hereby given, pursuant to section 10 (a) (2) of the Federal Advisory Committee Act (P.L. 92-463), that the next meeting of the National Advisory Council on Indian Education will be held on October 23-24, 1973, from 9:00 am. to 5:00 p.m. at the Northern Hotel, Billings, Montana.

Indian Education is established under The National Advisory Council un,

section 401 of the Indian Education Act (PL. 92-318, Title IV). The Council is

If review of the data submitted by an applicant or any other interested person directed to: warrants the conclusion that the drugs are safe for use for the labeling claims involved, the Commissioner will rescind this notice of opportunity for hearing.

If review of the data in the applica tion(s) and data submitted by the applicant(s) or any other interested person in a request for a hearing, together with the reasoning and factual analysis in a request for a hearing, warrants the conclusion that no genuine and substantial issue of fact precludes the withdrawal of approval of the application (s), the Commissioner will enter an order of withdrawal making findings and conclusions on such data.

If, upon the request of the new drug applicant(s) or any other interested person, a hearing is justified, the issues will be defined, a hearing examiner will be named, and he shall issue, as soon as practicable after October 26, 1973, a written notice of the time and place at which the hearing will commence. All persons interested in identical, related, or similar products covered by the new drug application(s) will be afforded an opportunity to appear at the hearing, file briefs, present evidence, cross-examine witnesses, submit suggested findings of fact, and otherwise participate as a party. The hearing contemplated by this notice will be open to the public except that any portion of the hearing that concerns a method or process the Commissioner finds entitled to protection as a trade secret will not be open to the public, unless the respondent specifies otherwise in his appearance.

Requests for a hearing and/or elections not to request a hearing may be seen in the Office of the Hearing Clerk

Advise the Commissioner in the preparation of general regulations and with respect to policy matters arising in the administration of this title, including policies and pr cedures governing the approval of State plans under section 318 and policies to eliminate duplication, and to effectuate the coordina tion of programs under this title and other programs offering Indian Education activities and services.

The Council shall review the administration and effectiveness of programs under this thereto, and make annual reports to the title, make recommendations with respect President of its findings and recommendstions (including recommendations changes in this title and other general laws relating to Indian Education activities and such report to the Congress together with its services). The President shall transmit each

comments and recommendations.

for

The meeting of the Council, under the authority of Section 10(b) of the Federal Advisory Committee Act (PL 92-463 and section 552(b) of Title 5 of the United States Code, will be partially closed to the public during the selection of nominees for the position of Deputy Commis sioner of Indian Education. The proposed agenda includes:

Executive Director's Report.
Committee Reports.

Selection of nominees for Deputy Commis

sioner of Indian Education. Review of Title IV Indian Education.

Indian Education Inter-Change.

Records shall be kept of all Council proceedings (and shall be available for public inspection at the Office of the National Advisory Council on Indian Education located at 425 13th Street, NW. Pennsylvania Bldg, Washington, DC 20004).