Hess & Clark, Division of Rhodia, Inc. v. Food & Drug Admin.

• Decision Date: 24 January 1974
• Docket Number: 73-1589.,No. 73-1581,73-1581
• Citation: 495 F.2d 975
• Parties: HESS & CLARK, DIVISION OF RHODIA, INC., Petitioner, v. FOOD & DRUG ADMINISTRATION et al., Respondents. VINELAND LABORATORIES, INC., Petitioner, v. Caspar W. WEINBERGER, Secretary, Department of Health, Education & Welfare, et al., Respondent.
• Court: U.S. Court of Appeals — District of Columbia Circuit

495 F.2d 975 (1974)

HESS & CLARK, DIVISION OF RHODIA, INC., Petitioner, v. FOOD & DRUG ADMINISTRATION et al., Respondents.

VINELAND LABORATORIES, INC., Petitioner, v. Caspar W. WEINBERGER, Secretary, Department of Health, Education & Welfare, et al., Respondent.

Nos. 73-1581, 73-1589.

United States Court of Appeals, District of Columbia Circuit.

Argued October 16, 1973.

Decided January 24, 1974.

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Eugene I. Lambert, Washington, D. C., for petitioner in No. 73-1581.

James L. Kaler, Washington, D. C., with whom Frederick S. Hird, Jr., Washington, D. C., was on the brief, for petitioner in No. 73-1589.

Robert M. Spiller, Jr., Atty., Food and Drug Administration, with whom Alvin L. Gottlieb, Deputy Asst. Gen. Counsel, Joanne S. Sisk, Chief, Appellate and Special Proceedings Branch, Food and Drug Administration, and Howard S. Epstein, Atty., Dept. of Justice, were on the brief, for respondent.

Before BAZELON, Chief Judge, and LEVENTHAL and ROBINSON, Circuit Judges.

LEVENTHAL, Circuit Judge:

Petitioners challenge an order of the Commissioner of the Food and Drug Administration (FDA), entered April 27, 1973, which withdrew approval of their New Animal Drug Applications (NADA's) for pellets of diethylstilbestrol (DES). They also challenge the Commissioner's order of May 3, 1973, issued ancillary to the withdrawal of the NADA's, and revoking certain use regulations. The Commissioner acted in the exercise of the authority conferred on the Secretary of Health, Education and Welfare by the Food, Drug and Cosmetic Act of 1938 (the Act) and delegated by the Secretary to the Commissioner.

We set aside the Commissioner's orders and remand the case to the FDA for further proceedings.

I. BACKGROUND OF FDA WITHDRAWAL ORDER

Pursuant to FDA approval of their NADA's, petitioners began manufacturing and selling DES in the 1950's.¹ DES is a synthetic estrogen which is fed to animals to increase their feeding efficiency; when given DES, animals gain weight more quickly with less feed. The drug is available in two dosage forms, a feed premix which the animals eat, and pellets which are implanted in the animal's ear.² Petitioners manufacture DES pellets.

DES has been recognized as a carcinogen for some years.³ As such the Delaney Clause⁴ would ordinarily have kept it from the market; the Clause automatically prohibits FDA approval of any drug that has been shown to be carcinogenic. But DES apparently passes out of the system of an animal in a very short time. An exception to the Delaney Clause is applicable if

the Secretary finds that, under the conditions of use specified in proposed labeling and reasonably certain to be followed in practice (i) such drug will not adversely affect the animals for which it is intended, and (ii) no residue of such drug will be found (by methods of examination prescribed or approved by the Secretary by regulations . . .) in any edible portion of such animals after slaughter or in any food yielded by or derived from the living animals . . .⁵

This clause, carving an exception out of the Delaney Clause, was enacted in 1962 with the DES situation in mind, and it is apparently sometimes referred to as the "DES clause."

Since 1962 the FDA has examined carcasses of slaughtered animals using its approved method of examination, the "mouse-uterine" test. To date this testing has revealed no DES residues in edible tissues under conditions of use of 10 milligrams of DES per head per day, combined with a minimum 48 hour withdrawal prior to slaughter. FDA accordingly continued approval of all NADA's for DES until 1972.

During 1971, however, the United States Department of Agriculture (USDA) began to test carcasses using a new method, Gas-Liquid Chromatography (GLC). The FDA represents that this method is quicker than the "mouse-uterine" test, and apparently more sensitive.⁶ Using the GLC test, the USDA detected small amounts of residue in beef livers, a fact which it reported to the FDA.

Acting on this information the FDA, on June 21, 1972, issued a Notice which was in form a notice to withdraw approval of NADA's for DES, but in substance a notice triggering a public hearing to develop pertinent information.⁷ The Notice cited increased public concern about the use of DES, and stated that

The Commissioner has concluded that the most appropriate forum for public consideration of this matter is a public hearing to develop on the public record the information necessary for a conclusion as to the proper handling of this matter. . . . Accordingly, the Commissioner has concluded that it would be appropriate to propose withdrawal of the approval of the new animal drug applications for DES in order to utilize the hearing mechanism provided in the statute for this purpose.⁸

The agency stated that it had not yet decided to withdraw approval for DES, and that it contemplated consideration of proposals that would provide both a check on misuse and more effective restrictions on use of DES to reduce illegal residues. It requested that the manufacturers' responses suggest protocols that would check such misuse and establish more effective restrictions on use of DES.⁹ The Notice then listed several types of information that the FDA wished to obtain from interested persons in the event a hearing were held.¹⁰

In accordance with agency regulations,¹¹ the Notice required interested parties requesting a pre-withdrawal hearing to file responses within thirty days, requesting such hearing and giving reasons why the NADA's should not be withdrawn. The petitioners responded within the thirty-day period.

Thereafter, on August 4, 1972, the FDA issued an order denying a hearing to the manufacturers of DES feed premixes, and withdrawing FDA approval of NADA's for premixes.¹² The order specified that the withdrawal of approval resulted from the failure of the manufacturers to come forward with practicable guidelines for curtailing abuses in the administration of DES by premix.¹³ But finding that the matter "is a regulatory, not a public health problem," with discontinuance of DES premix resulting from the inability to develop controls on the use of DES in animal feed that are reasonably certain to be followed in practice, and "because there is no evidence of a public health hazard," the FDA allowed the manufacturers to continue to sell their stocks of DES until December, 1972, and permitted the continued slaughter and marketing of cattle that had been fed DES.¹⁴

In denying a hearing, the Commissioner stated that the objections which he had received from premix manufacturers had failed to "set forth specific facts showing that there is a genuine and substantial issue of fact that requires a hearing."¹⁵ The FDA cited the USDA's particularized test results, which it found to be uncontroverted by any specific data in the responses.

With regard to implants, the FDA stated that the latest USDA study did not include implants, that earlier study had failed to detect any implant-related residues, and that therefore the implants could be continued on the market pending further study by the USDA.¹⁶ The order particularly recognized that the implants normally given to a cow during feeding placed into the cow's system one-thirtieth of the amount of DES which feed premix would place. The order advised that testing of implants had recently begun, utilizing the most recently evolved technique, radioactive tracer studies, with results expected within several weeks. For that reason, the Commissioner stated:

The Commissioner has therefore concluded that it is premature to rule at this time on the objections and requests for a hearing with respect to DES implants. A ruling on this matter will await the results of the USDA study now underway.

At the present time, the Commissioner has no reason to believe that DES implants raise a public health hazard. Thus, while it is prudent to pursue and to resolve existing scientific questions about DES implants, it is unnecessary to remove existing implants or to be concerned about the safety of meat from animals implanted with DES.¹⁷

Thus the FDA stated its intent "to pursue and resolve existing scientific questions about DES implants" through "the USDA study underway." It invited no further submissions from implant manufacturers.

Almost nine months passed. Then on April 27, 1973, the FDA issued an order withdrawing its approval of the NADA's for DES pellets, and denying a hearing to the petitioners.¹⁸ The order contained these findings:

The data obtained from the USDA radioactive-tagged DES implant study clearly establish the presence of residues of DES and/or its conjugates 120 days after implantation. No known data utilizing comparably sensitive methodology shows the absence of DES residues. The Commissioner and USDA are unaware of any valid basis for rejecting the results of this study as erroneous.

* * * * * *

The data now available in the NADA\'s demonstrate no residues only when tested by the mouse uterine and GLC methods, neither of which is sufficiently sensitive to permit a finding that no residue of DES exists 120 days after implantation.¹⁹

The order stated that the FDA had notified the petitioner of its intention to withdraw approval on June 21, 1972, that the petitioners' response to that notice had not raised any issues that required a hearing, and that the results of the latest USDA study made it impossible to allow the marketing of DES Pellets under any controls. Once again, the FDA stressed that the withdrawal was a regulatory matter and that:

. . . The Commissioner has no reason to believe that the use of DES implants has presented a public health hazard . . .²⁰

Accordingly, the order allowed the continued marketing of cattle which had already received DES by implant.²¹

Both petitioners challenge the validity of the April 27, 1973, Order on the ground, inter alia, that the Commissioner erred in failing to grant a pre-withdrawal...