Nor am I in a position to resolve questions concerning possible absorption problems associated with orally administered free estrogens. Compare Tr. at 29-30 (Dr. Archer) with Tr. at 82-86 (Dr. Krantz). As I stated earlier, the issue in this case is not actual safety and efficacy. That is a question committed to the FDA.
Rather, I must determine, under the standards explicated previously, whether the Hormonin products are "generally recognized" by qualified experts as safe and effective based upon "substantial evidence" as defined in the Act. I must conclude that they are not so recognized. I am convinced that both the government experts and those presented by Carnrick testified in accordance with their best professional judgment. There is no need to make credibility determinations. The lack of consensus among qualified experts concerning these products is manifest. While I do not believe unanimity is required, there is certainly "a genuine dispute among qualified experts" concerning the safety and efficacy of the Hormonin products. Carnrick submitted no "well-controlled" investigations concerning the combination of active ingredients in Hormonin. The evidence demonstrates that there is a paucity of scientific literature on the Hormonin products. Moreover, Estriol was never reviewed in DESI. The evidence concerning the protective function of Estriol is, at best, mixed. Tr. at 262-266 (Dr. Longcope), 357-359 (Dr. Vande Wiele), 468-469, 472 (Dr. Lemon).
Based on the foregoing, I conclude that the Hormonin products are not "generally recognized", based upon substantial evidence, among qualified experts as safe and effective for their labeled indications. As I have previously stated, I do not believe that the use "to a material extent or for a material time" affords a basis of "old drug" status independent of the "general recognition" standard. Having heard all the evidence, it appears to me that Hormonin is no more or less safe and effective than other estrogenic drugs. That, however, is not the issue. We are dealing with a narrow statutory exception from the premarketing clearance requirements of the Act. I do not hold that Hormonin is unsafe or inefficacious. However, since "general recognition" of the safety and efficacy of the Hormonin products has not been established, the products must be scrutinized by the FDA in the context of an NDA before they can be marketed. I conclude that the Hormonin products are "new drugs" within the meaning of the Act which have not received an approved NDA from the FDA and are, therefore, subject to seizure and forfeiture. 21 U.S.C. § 334.
I do not believe the 1964 opinion letter affords any basis for relief to Carnrick. Carnrick argues that the 1964 opinion letter, Claimants' Ex. N, O, concerning the formulation denominated Hormonin No. 1 forms the basis of an estoppel against assertion by the government that the Hormonin products are "new drugs". Carnrick contends that it relied, to its detriment, upon the opinion expressed by the FDA concerning marketing of Hormonin No. 1 and that the FDA never individually apprised Carnrick as to whether the 1964 letter was revoked.
The well-established general rule is "that the United States (is) neither bound nor estopped by the acts of ... (its) agents in entering into an ... arrangement to ... cause to be done what the law does not sanction or permit." Wilber Nat'l Bank v. United States, 294 U.S. 120, 122, 55 S. Ct. 362, 363, 79 L. Ed. 798 (1935); Utah Power & Light Co. v. United States, 243 U.S. 389, 409, 37 S. Ct. 387, 391, 61 L. Ed. 791 (1917); Lee v. Munroe & Thornton, 11 U.S. (7 Cranch) 366, 368-70, 3 L. Ed. 373 (1813); In re Hooper's Estate, 359 F.2d 569 (3d Cir. 1966). As stated in Federal Crop Ins. Corp. v. Merrill, 332 U.S. 380, 68 S. Ct. 1, 92 L. Ed. 10 (1947), "anyone entering into an arrangement with the Government takes the risk of having accurately ascertained that he who purports to act for the Government stays within the bounds of his authority. The scope of this authority may be explicitly defined by Congress or be limited by delegated legislation ... exercised through the rule-making power." Id. at 384, 68 S. Ct. at 3.
I note that the above stated general rule has been applied several times in the context of statements and representations made by agents of the FDA. Bentex Pharmaceuticals, Inc. v. Richardson, 463 F.2d 363, 368 n.17 (4th Cir. 1972), rev'd on other grounds, 412 U.S. 645, 93 S. Ct. 2488, 37 L. Ed. 2d 235 (1973); AMP, Inc. v. Gardner, 275 F. Supp. 410, 412 n.1 (S.D.N.Y.1967), aff'd, 389 F.2d 825 (2d Cir.), cert. denied, 393 U.S. 825, 89 S. Ct. 86, 21 L. Ed. 2d 95 (1968); United States v. 354 Bulk Cartons ... Trim Reducing-Aid Cigarettes, 178 F. Supp. 847, 853-54 (D.N.J.1959).
I believe that issuance of the 1964 opinion letter concerning the formulation known as Hormonin No. 1 was plainly beyond the statutory authority of the FDA. The 1962 amendments to the Act redefined "new drug" to include a drug not generally recognized as effective as well as safe. Such "new drugs" required premarketing clearance in the form of an NDA. 21 U.S.C. § 355(a), (b). There is absolutely no doubt that Hormonin No. 1 was a "new drug" under the statute in 1964. Carnrick never had an approved pre-1962 NDA for Hormonin No. 1 based upon safety. The combination of ingredients in Hormonin was not DESI reviewed. Estriol was never reviewed in DESI. There is no dispute that Carnrick's submission to the FDA in 1964 did not include the information required in 21 U.S.C. § 355(b). The FDA plainly had no legal authority to permit the marketing of Hormonin in 1964 without an NDA approved for safety and efficacy.
Moreover, the 1968 notice in the Federal Register plainly operated as a revocation of such letters. 33 Fed.Reg. 7758, see Hoffmann-LaRoche v. Weinberger, 425 F. Supp. at 893. Carnrick was aware, as early as 1967, that a clinical study of Hormonin was needed. Govt.Ex. 1103. There is evidence that Edmond J. Bergeron was informed prior to 1976 that an NDA for the Hormonin products was necessary because of the aforementioned notice. Govt.Ex. 1001 at 12-13. Although there was an ambiguous proviso in the Federal Register publication indicating that up to date opinions of the "new drug" status of drugs being marketed under such opinion letters would be forthcoming, the notice unambiguously states that the previously given letters were "revoked". 33 Fed.Reg. 7758. The FDA quite clearly had a duty to correct its position concerning these opinion letters when it became clear that the issuance of such letters was legally untenable. United States v. 60 28-Capsule Bottles, More or Less ... Unitrol, 211 F. Supp. 207, 215 (D.N.J.1962), aff'd, 325 F.2d 513 (3d Cir. 1963). The FDA recognized this duty in the notice published in the Federal Register.
Finally, no opinion letter was, apparently, ever secured relative to Hormonin No. 2. There is, accordingly, no basis for an estoppel concerning the marketing of that product.
I have a great deal of sympathy for Carnrick. In a very real sense Carnrick is the victim of bureaucratic ineptitude, the unwillingness of the FDA to follow the 1962 drug amendments and Congress' failure to provide FDA with the tools to accomplish the herculean task of reviewing all drug products for efficacy as required by the statute.
In my estimation, however, FDA had no authority under the statute to approve the marketing of Hormonin No. 1 in 1964 without an NDA. Accordingly, under the general rule enunciated above, the government is not estopped from asserting that the Hormonin products are "new drugs" under the Act. I have serious reservations as to whether equitable estoppel could ever be invoked to prevent enforcement of the policy of the Act, i. e., the protection of the public health and safety.
In sum, I find that Hormonin No. 1 and Hormonin No. 2 are "new drugs" within the meaning of 21 U.S.C. § 321(p). Hormonin No. 1 and Hormonin No. 2 have been introduced into interstate commerce without approval of an NDA. 21 U.S.C. § 355(a), (b). These drug products are, therefore, subject to seizure and forfeiture pursuant to 21 U.S.C. § 334(a). I find no basis upon which equitable estoppel may be applied against the government's assertion of "new drug" status of the Hormonin products.
Accordingly, judgment will be entered in favor of the United States forfeiting the seized quantities of Hormonin No. 1 and Hormonin No. 2. An order in conformity with this opinion will be submitted by the United States with consent as to form if possible.