Marshall Minerals, Inc. v. Food and Drug Administration

• Decision Date: 16 November 1981
• Docket Number: No. 80-7369,80-7369
• Citation: 661 F.2d 409
• Parties: MARSHALL MINERALS, INC., Petitioner-Appellant, v. FOOD AND DRUG ADMINISTRATION, Respondent-Appellee. . Unit B *
• Court: U.S. Court of Appeals — Fifth Circuit

Page 409

661 F.2d 409

MARSHALL MINERALS, INC., Petitioner-Appellant, v. FOOD AND DRUG ADMINISTRATION, Respondent-Appellee.

No. 80-7369.

United States Court of Appeals, Fifth Circuit.

Unit B ^*

Nov. 16, 1981.

Kirbo & Conger, Ben Kirbo, Bainbridge, Ga., for petitioner-appellant.

Food and Drug Administration, Dept. of Health, Education & Welfare, Nancy L. Buc, Frederick H. Degnan, Rockville, Md., Assoc. Chief Counsel for Veterinary Medicine, Appellate Section, Antitrust Div., U. S. Dept. of Justice, Robert B. Nicholson, Atty., Sanford M. Litvack, Asst. Atty. Gen., Daniel J. Conway, Dept. of Justice, Washington, D. C., for respondent-appellee.

Petition for Review of an Order of the Food and Drug Administration

Before MILLER ^**, Judge, and FRANK M. JOHNSON, Jr., and THOMAS A. CLARK, Circuit Judges.

MILLER, Judge:

This appeal is from the March 28, 1980, Food and Drug Administration ("FDA") final order, 45 Fed.Reg. 20,559, denying a request by Marshall Minerals, Inc. ("Marshall"), for a public hearing on its petition, dated August 12, 1977, for a food additive regulation pursuant to sections 409(b) and (c) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. §§ 348(b) and (c). ¹ We reverse

and remand for a public hearing pursuant to 21 U.S.C. § 348(f)(1), which provides for a public hearing on objections to an order by any person adversely affected thereby and action thereon by the Secretary by order made public.

BACKGROUND

Much of the relevant background for this case is reported in Southeastern Minerals, Inc. v. Harris, 622 F.2d 758 (5th Cir. 1980), and United States v. An Article of Food Consisting of 345/50-Pound Bags, 622 F.2d 768 (5th Cir. 1980), and need not be repeated here.

Marshall's petition relates to its gentian violet premix poultry feed. After the petition was filed and after the district court in Southeastern Minerals, supra, ruled that FDA had violated its own rules by failing promptly to notify Marshall of the disallowance of the petition, as noted by this court in Southeastern Minerals, supra at 762, FDA accepted the petition and published the proposed regulation. ² On May 8, 1978, however, FDA notified Marshall by letter that the stability data required under 21 C.F.R. § 571.1(A) still had not been received. ³ In this letter FDA first stated that its denial of the regulation was based on deficiencies in four areas: safety, utility, stability, and Environmental Impact Analysis Report ("EIAR"). FDA's position with respect to these four areas not only framed the issues in the subsequent proceedings before FDA but is crucial to resolution of the issue in this appeal. The letter stated that the data contained in Marshall's petition had been reviewed, but were inadequate for the following reasons:

A. Safety Data:

The submitted short-term toxicity studies reveal no clear adverse production effects of feeding gentian violet to chickens, however there were no histological examinations of tissues from the treated birds in those studies. The short-term duration of these studies and the lack of histological examination precludes assessment of the demonstrated carcinogenic potential of gentian violet .... The submitted residue data are identical to those data submitted by Naremco in 1974 ( ⁴ and conflict with other more recent data which indicate residues of gentian violet in edible tissues and eggs and which were derived from studies using significantly more sensitive detection methods.

B. Utility Data:

1. The studies reported in this submission concerning the inhibitory effects of gentian violet on growth of Aspergilli and other fungi and the biosynthesis of aflatoxins are not adequate to support the claim of utility in poultry feed. Most of these data have been generated from studies in which laboratory media were used as the substrate for fungal growth. The utility of gentian violet must be demonstrated.

2. The Somporn Study, ( ⁵ part of which was conducted in feed, indicated that crystal violet had no inhibitory effect on Aspergilli in feed when the dye was added at 150 ppm. This concentration is approximately ten times the proposed use level.

3. The submitted report by Kingsland and Anderson does not qualify as supportive data for utility because of experimental deficiencies.

a. No zero time samples were taken to determine the level of contamination

of the feed prior to inoculation with the test organisms.

b. Experimental conditions during the 12 week feed incubation period were not specified.

c. Isolates from the uninoculated controls were not identified. Therefore, the fungi growing in the feed could have been any fungi including those used to inoculate.

d. If the fungal counts from the uninoculated controls are compared after 12 weeks of incubation it is evident that a tremendous amount of variation occurred among them (range of 4.3 X 10 3 to 1.9 X 10 7). This variation in background contamination makes it impossible to draw conclusions about the effectiveness of gentian violet on the test organisms because the proportion of total counts due to contaminants in the treated feed is unknown.

C. Stability Data:

As noted above and in our letter of January 23, 1978, ( ⁶ another inadequacy in your petition is the lack of stability data specified under and required by 21 C.F.R. 571.1(A).

(D. EIAR is covered in Conclusion 4, infra.)

Conclusions:

1. Properly designed and carefully conducted and controlled chronic toxicity studies in test animals must be performed and completed. Studies reported in your submission are inadequate to determine long-term effects of feeding gentian violet. Therefore, it is impossible to evaluate the safety to humans from the use of your product under the conditions of intended use.

2. Adequate studies to demonstrate the utility of gentian violet as (a) fungistat in feed above have not been conducted.

3. It is apparent from studies reported elsewhere that fungi differ considerably in their sensitivity to gentian violet. Therefore, the fungi against which gentian violet is effective at the proposed concentration for use will have to be specified.

4. The (EIAR) submitted with your petition is incomplete. See Title 21 CFR 25.1. Specific data supporting safety of gentian violet and specific details of the blending process were not included. Final analysis of your EIAR is not possible until the pending questions on safety have been resolved and until the details of your blending process have been submitted.

Pursuant to the decision of the District Court, entered on April 19, 1978, your petition has been deemed "filed". Notice of the regulation you have proposed will be published in the Federal Register within 30 days of April 19, 1978. This letter constitutes a determination, on the merits of the data you have submitted, that your petition is inadequate and, as submitted, would not support such a Food Additive regulation. Consistent with agency policy and in accord with the Court's decision, you have thirty days to advise us whether, and if so, how you intend to satisfy the serious deficiencies in your petition. In the absence of the required data, an order consonant with the data submitted will be issued.

In response to FDA's letter, Marshall stated in a letter dated July 7, 1978, that it intended to maintain its position that gentian violet in general as well as in its premix is not subject to the Food, Drug and Cosmetic Act because gentian violet is generally recognized as safe. See United States v. An Article of Food Consisting of 345/50-Pound Bags, 622 F.2d at 770.

In regard to the alleged safety deficiencies Marshall declined to respond, requesting definition from FDA for the terms "short-term" and "long-term" in the context of gentian violet toxicity studies as well as copies of the "other more recent In regard to the alleged utility deficiencies Marshall stated that the "mere fact that some of the work has been generated from studies in which laboratory media were used as the substrate for fungal growth does not preclude their value as supported (sic supportive) data for such utility claim." Marshall also noted "that the sections of Food and Drug Administration law regarding the food additive petition are directed more toward safety than toward utility ... (and assumed) ... that any problems regarding utility would work themselves out in the market place, for certainly if the product does not work the consumer will not purchase it."

data" referred to in FDA's May 8, 1978, letter. Marshall indicated that it would respond after it had reviewed this requested information.

Regarding the "Somporn Study" comments in the May 8, 1978, FDA letter, Marshall explained "that the claim of Marshall Minerals is not for specificity of action against Aspergilli, but as an aid in the control of fungus and mold growth in poultry feed." Marshall pointed to data in the "Somporn Study" on four fungi or molds under varying conditions with gentian violet concentrations of from 15-80 parts per million ("ppm") showing growth inhibitions ranging from partial to complete, and concluded from these data that its utility claim was clearly supported. ⁷

As to the report of Kingsland and Anderson, Marshall submitted a letter and statement by Mr. Graydon C. Kingsland, Associate Professor in the Department of Plant Pathology and Physiology at Clemson University and coauthor of the study, the relevant portions of which follow:

a. Zero time values for propagules of the test fungi in the feed are the values labeled "Unaltered Controls" in Table 2. These values were obtained from dilutions of the unaltered feed. Relatively little, if any, growth or sporulation would be expected at 8.5% moisture. These values, consequently, are probably good approximations of the level of original contamination.

b. The samples were stored under general laboratory conditions with temperatures between 70o and 76o F. This is near the optimum temperature for growth and development of F. moniliforme. It is 8o...