# Petition for Writ of Certiorari — Efamol, Ltd. v. United States > Briefs, arguments, decisions, and more. URL: https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386011_1042%3A1 ## Record - **Collection:** Supreme Court brief - **Document type:** Petition for Writ of Certiorari - **Published:** January 1, 1992 - **Citation:** 506 U.S. 940 ## Text Supreme Court, U.S, rFiLeD 992-173 JUL 28 1992 GFFICE OF THE “p | No. 92- — c CLERK come IN THE Supreme Court of the United States OCTOBER TERM, 1992 EFAMOL, LTD., Petitioner, f €titiviieciy, vs UNITED STATES OF AMERICA, Respondent. ON PETITION FOR WRIT OF CERTIORARI TO THE UNITED STATES COURT OF APPEALS FOR THE NINTH CIRCUIT PETITION FOR WRIT OF CERTIORARI JAMES R. PHELPS Counsel of Record ROBERT A. DORMER A. WES SIEGNER, JR. MARY BETH NERAAS HYMAN, PHELPS & McNAMARA, P.C. 700 Thirteenth Street, N.W. Suite 1200 Washington, D.C. 20005 (202) 737-5600 July 28, 1992 Attorneys for Petitioners Balmar Legal Publishing Services, Washington, D.C., (202) 68209800 i QUESTIONS PRESENTED 1. Should this Court permit the Ninth Circuit, in conflict with other circuits and the plain language of the Federal Rules of Evidence, to use Rule 703 of the Federal Rules of Evidence and Frye v. United States, 293 F. 1013 (D.C. Cir. 1923), to exclude from the jury on a motion for summary judgment more than 300 pages of expert testimony that is based upon facts and data routinely and reasonably relied upon by experts in the field to make the type of food safety determination at issue in this case’ 2. Should this Court permit the Ninth Circuit, in conflict with other circuits, the Federal Food, Drug, and Cosmetic Act (FDC Act), and the legislative history of the FDC Act, to shift to manufacturers of food products the burden of proving in a seizure action that the food in question is “generally recognized as safe” for its intended use within the meaning of the FDC Act, 21 U.S.C. § 321(s} (1992)? 3. Is there a genuine issue of materia! fact as to whether the food at issue is “misbranded” within the meaning of the FDC Act, 21 U.S.C. § 343 (1992)? 1] TABLE OF CONTENTS QUESTIONS PRESENTED OPINIONS BELOW JURISDICTION STATUTORY PROVISIONS INVOLVED STATEMENT OF THE CASE . 1. Statutory And Regulatory Framework a. Statutory and regulatory requirements pertaining to general recognition yf Safety |) Data from unpublished studies 2) Drug study data b. Statutory and regulatory requirements pertaining to misbranding Proceedings In The District Court... . WwW Proceedings In The Court of Appeals REASONS FOR GRANTING THE WRIT ..... 1. This Court Should Resolve The Conflict In The Circuits Over Fed. R. Evid. 703 And a a. The split in the circuits over Fed. R. Evid. 703 and the Frye test b. The test that should be used by the courts The Supreme Court Should Resolve The Conflict As To Which Party Bears The Burden Of Proof On The Issue Of GRAS Status ..... Pages > ho W 3 »~6Efamol’s Fvidence On The Misbranding Issues Raises Genuine Issues Of Fact Requiring A Trial Li CONCLUSION 1 TABLE OF AUTHORITIES (Cases Pages a Ambrosini 3 Labarraque, No. 90-7 \4¢ ind No. 90-714&,. shi D.C. Cir. June 12. 1992 Anderson v. Liberty Lobby. J) 5-7-9 ieee ae . + S. 242 (19%6 f Beech Aircraft Corp Raine, Le ) wat 188 U.S. 153 (198% Christophersen v. Allied Signal Corp No. W-®&-CA-09% slip Op (W.D. Tex October 12, 1989), aff d en han 939 F.2d 1106 (Sth Cir. 1991), cert. denied U.S 112 S. Ct. 1280 (1992) (White & Blackmun, J.J., dissenting from denial of certiorari) passim Clinchfield R.R. Co. v. Lynch, 7&4 F.2d 545 (4th Cir. 19&6) . . 1%, 23 Daubert v. Merrell Dow Pharmaceuticals. Ine 951 F.2d 1128 (9th Cir. 1991), petition for cert filed No 92 102 (July 7 1992) Dass m DeLuca v. Merrell Dow Pharmaceuticals. Ini 911 F.2d 941 (3d Cir. 1990'. summan judgment granted on remand, No. 87-226 (GEB), 1992 U.S. Dist. LEXIS 6511 (D.N.J. April 29, 1992) 16, 17, 20, 23 Ellis v. Int'l Playtex, In (4th Cir l 984) Fmali Herb, Inc. v. Heckler. 715 F.2d 1385 (Oth Cir. 1983) 28 Frvey.l ‘nited States, 293 F 1013 = (D.C. Cir. 1923 passim Pages Head v. Lithonia Corp., Inc., 881 F.2d 941 PH Le. SOY cg ss mace eel es 20 In re “Agent Orange” Prod. Liab. Litig., 611 F. Supp. 1223 (E.D.N.Y. 1985), aff'd on other grounds, 818 F.2d 187 (2d Cir. 1987), cert. denied, 487 U.S. 1234 (1988) 14.19 - Int'l Adhesive Coating Co., Inc. v. Bolton Emerson Int'l, Inc., 851 F.2d 540 (1st Cir. 1988). 17 Japanese Elec. Prod. Antitrust Litig. v. Matsushita lec. Indus. Co., Ltd.., 723 F.2d 238 (3d Cir. 1983), rev'd on other grounds sub nom., Matsushita Elec. Indus. Co., Ltd Zenith Radio Corp., 475 U.S. 574 (1986) 14 Kropinski v. World Plan Executive Council - U.S., 853 F.2d 948 (D.C. Cir. 1988). ae 20 Mannino vy. Int'l Mfg. Co., 650 F.2d 846 1 2 ae Loo Ze oes are ese 18, 23 Mustafa v. United States, 479 U.S. 953 (1986) (White & Brennan, J.J., dissenting from denial of certaOnGMi) ww wk 16 Nat'l Labor Relations Bd. v. Transport. Management Corp., 462 U.S. 393 (1983) . . . 26 Rogers v. Raymark Indus., Inc., 922 F.2d 1426 ‘A ey dt eee eon Ao 1X Udall v. Tallman, 380 U.S. 1 (1965) ........ 28 United States v.46 Cases, More or Less . .. “Welch's Nut Caramels * * *,” 204 F. Supp. S21 (DRL. IFS) 2. es eee ee 26 (/nited States v. 88 Cases, More or Less, Bireley' s Orange Beverage, 187 F.2d 967 (3d Cir.), cert. denied, 342 U.S. 861 (1951) U/nited States v. 119 Cases, More or Less New Dextra Brand Fortified Cane Suga 231 F. Supp. 551 (S.D. Fla. 1963), aff'd per curiam, 334 F.2d 238 (Sth Cir. 1964) (/nited States v. 217 Cases Efamol Evening Primrose Oil. No Q? BF int. 1B (D. Utah filed June 1, 1992) / } ited States \ A hel. 469 [ S 45 { 1QK4 U/nited States v. Alcon Lab., 636 §.2d &76 (1st ¢ cert. denied, 451 U.S. 10)7 {198] U/nited States v. An Article of Drug Bentex Uleerine,” 469 F.2d %75 (Sth Cir. 19 cert. denied, 412 U.S. 93% (1973 United States v. An Article of Food Coco Rico 752 F.2d 11 (1st Cir. 1985) 2t United States v. An Article of Food FoodScience Lab., Inc., 678% F.2d 735 (7th Cir. 1982 United States v. An Article of Food 345/50 Pound Bags, 622 F.2d 768 (Sth Cir. 1980 United States v. Articles of Food and Drug Coli-Trol, 372 F. Supp. 915 (N.D. Ga. 1974 aff d, 518 F.2d 743 (Sth Cir. 1975) ~y United States v. Dixon, 547 F.2d 1079 (Oth Cir. 1975) United States v. Downing, 753 F.2d 1224 (3d Cir. 1985) Vii United States v. Ewig Bros. Co., Inc., 502 F.2d 715 (7th Cir. 1974), cert. denied, oe 3 ty 7 | a eee 28 United States v. General Foods Corp.. 446 F. Supp. 740 (N.D.N.Y.), aff d, 591 F208 1332 (2a Cir. 1978) . ww 26 United States v. Grajeda, 570 F.2d 872 (9th Cir. ), withdrawn and new opinion issued on alternate ground, 587 F.2d 1017 (9th Cir. 1978) .. . . 24 United States v. Jakobetz, 955 F.2d 786 (2d Cir. 1992), petition for cert. filed, No. 91-7921 (April 8, 1992) ......... passim United States v. Kail, 804 F.2d 441 eRe, INN 0 ore aking gk ek aw 18 United States v. Metzger, 778 F.2d 1195 UO | a a Cra ena 19 United States v. Rogers, 918 F.2d 207 Fe ED ere ee ee Fk we Se 24 United States v. Smith, 869 F.2d 348 Po CN 6m ee ace ee eS 16, 19 United States v. © slomon, 753 F.2d 1522 Pee EU a one os ae a ee 20 United States v. Two Bulls, 918 F.2d 56 CR EME 3258 a - G oe bo 3 88s 16, 20 United States v. Tranowski, 659 F.2d 750 (7th Cir. 1981), rev'd on other grounds, 702 F.2d 668 (1983), cert. denied, 468 U.S. Bre Se ne. a tae ee ek 18 United States v. Western Serum Co., Inc., 666 F.2d 335 (9th Cir. 1982) .. 2... 29 Weinberger v. Bentex Pharmaceuticals, Inc.., 412 U.S. 645 (1973) Zuber v. Allen, 396 U.S Regulations, Statutes and Public Laws Crk. a Sh C.F.R ot Ok it FF Ci.R Crus rr we A U.S.C U.S.C Ly ke U.S.C USA... U.S.C. U.S.C. OS Be Lok. U.S.C USA. USA. Part 182 (1991) torn wor Or LQ ven Or tr Gr LM . Part 184 (1991) 101.100(d) (1991) 101.100(d)(2) (1991) 170.3(h) (1991) 170.30(b) (1991) 170.30(d) (1991) 170.35 (1991) 1$2.1(a) (1991) 321(f) (1992) 321(s) (1992) 334 (1992) 334(a) (1992) 334(d) (1992) 334(d)(1) (1992) 342(a)(1) (1992) 342(a)(2)(C) (1992) 342(a)(3) (1992) § 343(a) (1992) uP unr 343(a)(1) (1992) 343(b) ( 1992) 16% { 1969) d& | 4 gee 4 £ QS V4 4 4 ISSIUM - £ a. + 4\ 2 4 5. 27 % - 6 ~ 343; 1) { 1992) 2i U.S.C. LN AY Us SP 21 U.S.C. § 348 (1992) 21 U.S.C. § 348(a) (1992) 28 U.S.C. § 1254(1) (1992) 28 U.S.C. § 2072-74 (1992) Pub. L. No. 75-717, 52 Stat. 1050 (1938) Pub. L. No. 85-929, 72 Stat. 1784 (1958) Pub. L. No. ‘ ~~ 3-595. 88 Stat. 1926 (1975) Rules Federal Rules of Evidence Rule 403 Rule 703 Miscellaneous 42 Fed. Reg. 38,609 (July 29, 1977) 42 Fed. Reg. 41,876 (August 19, 1977 343(1)(1) (1992) d. 43 Fed. 43 Fed. 48 Fed. 48 Fed. 55 Fed. 55 Fed. Reg. 14,064 (April 4, 1978) Reg. 31,349 (July 21, 1978) Reg. 239 (January 4, 1983) Reg. 5716 (February 8, 1983) Reg. 6384 (February 23, 1990) Reg. 10,932 (March 23, 1990) 3 Jack B. Weinstein & Margaret A. Berger, Weinstein’ s Evidence § 703[(01] (1991) 22 C. Wright & K. Graham, Federal Practice and Procedure § 5169 (1978) Pages 8, 30 12,13 5 99 5 } I . : 19 passim 6 5 i) - Pages Chemical Additives in Foods: Hearings Before a Subcomm. of the House Comm. on Interstate and Foreign Commerce, 84th Cong., 2d Sess. 226 (1956) 28 Edward J. Imwinkelreid, The Standard For Admit- ting Scientific Evidence: A Critique From The Perspective Of Juror Psychol ey, 28 Vill. L. Rev. 554 (1982-83) hm 7 Edward J. Imwinkelried, The “Bases” Of Expert Testimony: The Syllogistic Structure Of Scientific Testimony, 67 N.C.L. Rev. 1 Gok oe ak awe ke wk ee ae a 15, i i” Faust F. Rossi, Modern Evidence and the Expert Witness, 12 Litig. 18 (Fall 1985) ....... 22 Food Additives: Hearings Before a Subcomm. of the House Comm. on Interstate and Foreign Commerce, 85th Cong., 2d Sess. Eos hata nee er at Aa tare eth ata a Le 27 Gary Taylor, Expert Witness Opinion Eyed; Circuits Split on Issue, Nati L.J. (Oct. 21,1991) ... 16 Michael C. McCarthy, Note, “Helpful” Or “Reasonably Reliable” ? Analyzing The Expert Witness s Methodology Under Federal Rules Of Evidence 702 And 703, 77 Cornell L. Rev. 350 (Jan. 1992) ... 14, 16, 19, 20 Recent Case, 105 Harv. L. Rev. 791 (1992) .... 22 S. Rep. No. 93-1277, 93d Cong., 2d Sess. (1974), reprinted in 1974 U.S. Code Cong. & Admin. ee ee 4k eS ee ee 24 ————————— OPINIONS BELOW The decision of the United States Court of Appeals for the Ninth Circuit affirming the District Court’s grant of summary judgment for respondent is dated April 7, 1992, is not yet reported, and is reprinted in the Appendix at A-1. (References to the appendices bound with this petition are styled “A-__”.) On June 12, 1992, the Ninth Circuit denied petitioners’ petition for rehearing and suggestions for rehearing en banc. A-11. On June 29, 1992, the Ninth Circuit granted petitioners’ motion for stay of the mandate. A-12. The Order of the United Stutes District Court for the Central District of California granting respondent's motion for summary judgment, from which appeal was taken, is dated November 27, 1989, is unreported, and is reprinted in the Appendix at A-17. JURISDICTION The decision of the Court of Appeals was announced on April 7, 1992, and the petition for rehearing and suggestions for rehearing en banc was denied on June 12, 1992. The jurisdiction of this Court is invoked under 28 U.S.C. § 1254(1) (1992). STATUTORY PROVISIONS INVOLVED The Federal Rules of Evidence were enacted by Congress as a Statute in 1975, Pub. L. No. 93-595, 88 Stat. 1926 (1975), 28 U.S.C. §§ 2072-74 (1992). Rule 703 provides: Rule 703. Basis of opinion testimony. The facts or datain the particular case upon which an expert bases an opinion or inference may be those perceived by or made known to the expert at or before the hearing. If of a type reasonably relied upon by experts in the particular field in forming opinions or inferences upon the subject, the facts or data need not be admissible in evidence. 2 The Federal Food, Drug, and Cosmetic Act (FDC Act), Pub. L. No. 75-717, 52 Stat. 1050 (1938), amended by The Food Additives Amendment of 1958, Pub. L. No. 85-929, 72 Stat. 1784 (1958), 21 U.S.C. § 321(s) (1992), A-18, states that: The term “food additive” means any substance the intended use of which results or may reasonably be expected to result, directly or indirectly, in its becom- ing a component or otherwise affecting the charac- teristics of any food . . . if such substance is noi generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures . . . to be safe under the ccndi- tions of its intended use... . This case also involves the FDC Act’s provisions relating to “adulteration,” 21 U.S.C. §§ 348(a) and 342(a)(2)(C) (1992), and “misbranding,” 21 U.S.C. §§ 243(a)(1) and (i)(1) (1992). The applicable provisions are reproduced in the Appendix, A-i9-21. STATEMENT OF THE CASE This is an in rem seizure action brought under the FDC Act of bulk drums of a vegetable oil, evening primrose oil (EPO). The primary issue is whether under Rule 703 of the Federal Rules of Evidence, or the common-law Frye test, the affidavit testimony of informed experts in the field of food safety may be disregarded by the trial and appellate courts. This is also a case in which only one side has been heard. The district court granted the Food and Drug Administration’s (FDA’s) motion for summary judgment on a scientific issue that Congress said was to be determined by qualified experts. The district court failed even to mention the evidence in over 300 pages of testimony from eleven internationally recognized experts, includ- ing a Nobel Prize recipient and a former Deputy Associate FDA Commissioner. ns 35 The Ninth Circuit affirmed, deeming Efamol’s testimony “contaminated by . . . consideration of unsuitable evidence” and therefore inadmissible under Rule 703 and under the Frye test.! United States v. 45/194 Kg. Drums of Pure Vegetable Oil, No. 90-55086, at A-8-9 (9th Cir. April 7, 1992) (hereinafter referred to as “Opinion at A-__””). The result is the bizarre rejection of the kind of evidence that all experts, including FDA’s, rely upon in making food safety evaluations. The Ninth Circuit’s ruling calls into question a fundamen- tal aspect of the admissibility of expert testimony and an issue upon which the circuits are in disagreement: Can Rule 703 of the Federal Rules of Evidence be used by judges to reject litigants’ expert opinions, and can courts impose the common- law Frye test to require that an expert’s methodology be general- ly accepted within the scientific community? The Ninth Circuit’s decision raises another issue in which the circuits are in disagreement: In a seizure action under the FDC Act, does FDA bear the burden of proving that the sub- stance at issue is not “generally recognized as safe” and is therefore a food additive? 1. Statutory And Regulatory Framework. The government seeks condemnation of bulk drums of EPO pursuant to the FDC Act, 21 U.S.C. § 334(d)(1) (1992). The drums of EPO, owned by petitioner, Efamol, Ltd. (Efamol), remain under seizure. The EPO is intended to be mixed with a preservative, vitamin E, encapsulated in gelatin capsules, and sold as a dietary supplement of essential fatty acids.2_ EPO is sold as a dietary supplement in more than 25 countries, including Frye v. United States, 293 F. 1013, 1014 (D.C. Cir. 1923), provided that before a proponent may introduce testimony based on a novel scientific technique, the proponent must prove that the technique is already generally accepted within the relevant scientific specialty. Panel Report on the Status of EPO as “Generally Recognized as Safe,” excerpts of the record submitted to the Ninth Circuit (hereinafter referred to as “Exc.”) at 105 n.1 and 116 n.11. 4 countries such as the United Kingdom, Japan, Germany and France, which have regulatory systems that are as sophisticated as FDA’s. Exc. at 376, 387, 1042. FDA asserts that the EPO should be condemned (1) be- cause EPO is not generally recognized as safe and is therefore a “food additive” for which there is no FDA approval, and (2) because the seized product is “misbranded.”? a. Statutory and regulatory requirements pertaining to general recognition of safety. The Ninth Circuit struck all of Efamol’s expert testimony based upon the erroneous determination that experts in the field of food safety are prohibited from considering data from un- published studies and from studies in which a substance was used as a drug — rather than as a dietary supplement — in determining whether the substance is generally recognized as safe (GRAS). See Opinion at A-8-9. ; The FDC Act defines the term “food” as “articles used for food or drink for man. . . [and] articles used for components of any other such article.” 21 U.S.C. § 321(f) (1992). Under the FDC Act. a food ingredient intended to become a component or otherwise affect the characteristics of a food can be used without prior FDA approval if it is generally recognized, among experts qualified by scientific training and experience to evaluate its 3 Whether EPO is generally recognized as safe or whether it is a “food additive” will determine whether the substance may be sold in the United States. FDA has recently seized a large quantity of EPO in another action, United States v. 217 Cases . . . Efamol Evening Primrose Oil, No. 92-C- 0584B (D. Utah filed June 1, 1992), also alleging that EPO is an unapproved “food additive.” The misbranding issues are peculiar to the particular product seized in the instant case, and can easily be resolved under the “reconditioning” provision of the FDC Act. 21 U.S.C. § 334(d) (1992), by relabeling the product. Efamol maintains that the product is not misbranded. Efamol is nonetheless willing to stipulate to relabeling the product to comply with FDA’s wishes. 5 safety, as having been adequately shown through scientific procedures . . . to be safe under the condi- tions of its intended use. . . . 21 U.S.C. § 321(s). Beyond this, the FDC Act does not specify any other requirements for establishing the GRAS status of a particular food ingredient. Food ingredients that are “generally recognized as safe” are referred to by food safety experts as “GRAS” substances. Many foods similar to EPO, including vegetable oils such as corn oil. soybean oil, and safflower oil, are GRAS and are marketed without FDA approval. FDA’s regulations contain a partial list of substances the agency regards as GRAS. 21 C.F.R. Parts 182 and 184 (1991). FDA recognizes that, because the number of GRAS substances is so large, “{iJt is impracticable to list all substances that are generally recognized as safe for their in- tended use.” 21 C.F.R. § 182.1(a) (1991): see also id. at § 170.30(d) (1991). FDA’s primary basis for condemnation is that EPO is not GRAS and is therefore a “food additive” within the meaning of 21U.S.C. §321(s). Because FDA has not published a regulation permitting its use, 21 U.S.C. § 348 (1992), FDA argues that EPO is an “adulterated food” pursuant to 21 U.S.C. § 342(a)(2)(C). Adulterated foods are subject to seizure under 21 U.S.C. § 334 (1992). 1) Data from unpublished studies. FDA’s regulations, similar to the FDC Act, provide broad standards for GRAS status. The courts below took no notice of the fact that FDA’s regulations define the term “scientific pro- cedures,” as used in the FDC Act, 21 U.S.C. § 321(s), as “human, animal, analytical, and other scientific studies, whether publish- ed_ or unpublished, appropriate to establish the safety of a substance.” 21 C.F.R. § 170.3(h) (1991) (emphasis added). FDA’s regulations further state that “[g]eneral recognition of fy safety through scientific procedures shall ordinarily be based upon published studies which may be corroborated by un published studies and other data and information.” 21 C.F.R § 170.30(b) (1991) (emphasis added). FDA’s regulations therefore specifically contemplate con sideration of unpublished studies in GRAS evaluations. FDA’s regulations do not define what studies are ~appropriate” to GRAS evaluations, or what “other data and information” may or may not be considered. However, food safety experts, both within and outside FDA, routinely rely on unpublished studies as well as data from drug studies for the purpose of GRAS evaluations. FDA’s own published GRAS “affirmations” establish that the agency itself has relied extensively on unpublished data in GRAS evaluations.4 In its GRAS affirmation of corn syrup made from bacteria, 48 Fed. Reg. 5716 (February 8, 1983), A-71, FDA stated that “[u]npublished pathogenicity studies . . . show that these organisms are neither pathogenic nor toxicogenic . . . .” A-74, 78.5 FDA also considered “un published animal feeding studies” for this GRAS evaluation. Id.° More recently, FDA has relied on unpublished data to corroborate the agency’s GRAS affirmations for Simplesse®, a fat substitute, and chymosin, an enzyme used to clot milk.” Although the FDC Act does not require FDA approval of GRAS food ingredients, companies may request that FDA “affirm” a company’s GRAS determination. 21 C.F.R. § 170.35 (1991). FDA publishes its proposed and final regulations pertaining to such GRAS affirmations in the Federal Revis- ter as well as the final in the Code of F ederal Regulations. 21 C.F.R. Part 184 The Federal Register announcements cited here were included in an addendum to Efamol’s appellate brief. The announcements are duplicated. and the applicable portions underlined, in the Appendix to this Petition for the Court’s convenience. See also 48 Fed. Reg. 239, 240 (January 4, 1983), A-86, 89. ' §5 Fed. Reg. 6384, 6386-87, 6390 (February 23, 1990), A-48-51, 59. 62-63; 55 Fed. Reg. 10,932 (March 23, 1990), A-24, 33. / FDA’s former Deputy Associate Commissioner for Health Af fairs, Dr. Joseph V. Rodricks, further establishes that e Xperts engaged in GRAS evaluations routine ly consider unpublished data as part of the evaluation. Exc. at 1057-&. © 16.2 2) Drug study data. FDA’s published record of GRAS evaluations establishes unequivocally that food safety experts depend on data from dru studies to perform GRAS evaluations Examples of such reliance include FDA’s GRAS affirmation of beeswax (used in food as a flavoring agent and for other uses). 42 Fed. Reg. 3% 609 (July 29, 1977), A-138, 141-42, papain (an enzyme used in beer processing, cooking, and meat tenderizing ), 43 Fed. Reg. 31,349 (July 21, 1978), A-93, 98-99, agar-agar (a polysaccharide ex tracted from algae used to make candy), 42 Fed. Reg. 41.876 (August 19, 1977), A-125, 131, and ammonium compounds (used a agen ong purpose food substances), 43 Fed. Reg. 14.064 (April 4, 1978), A-107, 114. In addition, the te sumony of Efamol’s experts establishes that drug studies provide v aluable safety information and therefore should be considered in any GRAS evaluation of EPO used as a dietary supplement. Exc. at 687-9, 4 10; Exc. at 1056-7, 94 12-15; and Exc. at 1041-2. 9 16. b. Statutory and regulatory requirements pertaining to misbranding. FDA has alleged, as alternative grounds for condemnation of the seized product, that the product is misbranded within the meaning of 21 U.S.C. §§ 343(aj(1) and (ij(1) because it is labeled “Pure Vegetable Oil” rather than “Evening Primrose Oil.” Section 343(a)(1) states that a food is misbranded if its labeling is “false or misleading in any particular.” Section 343(1)(1) requires that the label of most foods bear “the common 5 While at FDA, Dr. Rodricks had special responsibility for risk and safety assessment of foods. Exc. at 394, 4 1. He has also served as a member and has chaired several committees of the National Academy of Sciences. and has testified before the United States Congress as an expert on issues relating to food safety and risk assessment. /d or usual name of the food... .° FDA has promulgated regulations exempting under specified conditions foods that are intended for further processing from the “common or usual name” requirement. 21 C.F.R. § 101.100(d) (1991). A-22. 2. Proceedings In The District Court. The bulk drums of EPO at issue in this case were seized on January 31, 1989. Efamol submitted a claim requesting a jury trial on February 13, 1989. FDA submitted a motion for sum- mary judgment on May 22, 1989. In support of FDA’s allega- tion that evening primrose oil is not GRAS, FDA submitted 48 pages of testimony consisting of the declarations of two FDA employees and four outside scientists. Exc. at 33-80. FDA also submitted a declaration and documentary evidence to support its allegation that the seized product is misbranded pursuant to 21 U.S.C. §§ 343(a) and (i)(1).? On August 22, 1989, Efamol submitted a cross motion for summary judgment in opposition to FDA’s motion for summary judgment. Efamol argued that FDA-had the burden of proving that EPO is not GRAS, that the published literature as reviewed and analyzed by Efamol’s experts established that EPO is GRAS, and that the product was not misbranded. Efamol argued that at a minimum it was entitled to a jury tral. Prior to responding to FDA’s summary judgment motion, Efamol convened a panel of experts to consider the GRAS status of EPO. The panel included: Uno O. Barcelli, M.D., Associate Professor of Clinical Medicine, University of Cincinnati Medical Center. David J. Everett, B.Sc.; Head of Rodent and Reproductive Toxicology and Study Director at Inveresk Research Inter- national, Scotland. ° Efamol does not contest that the common or usual name of the seized product is evening primrose oil, but maintains that the seized product is exempt from the “common or usual name” requirement, as discussed below. 9 Robert S. Fisher, M.D., Ph.D., Associate Professor of Neurology/Neurosurgery, and Co-director, Epilepsy Cen- ter, The Johns Hopkins University. Ralph T. Holman, Ph.D., Emeritus Professor of Biochemistry, University of Minnesota, Minneapolis: Professor in Mayo Medical School, Rochester, Minnesota. Loren D. Koller, Ph.D., D.V.M., Professor and Dean. College of Veterinary Medicine, Oregon State University, Corvallis, Oregon. Asaf A. Qureshi, Ph.D., Senior Scientist at the Wisconsin Analytical and Research Services, Ltd. and President of Advanced Medical Research, Madison. Wisconsin. Adrianne E. Rogers, M.D., Professor of Pathology, As- sociate Chairman of Pathology for Academic Affairs, and Director of Graduate Studies in Pathology, Boston Univer- sity School of Medicine. Robert G. Tardiff, Ph.D., Director, Riskfocus, Versar Inc.. Springfield, Virginia. Stephen Wright, M.D., Consultant Senior Lecturer in Der- matology, The Royal Free Hospital School of Medicine, London. Exc. at 105-6. Efamol’s evidence on the issue of EPO’s GRAS status consisted of a joint declaration by the expert panel, Exc. at 105-53, individual declarations from each of the panel ex- perts, Exc. at 154-325, additional declarations from four of the panel members, Exc. at 495-709, 1030-46, and declarations from Dr. Joseph V. Rodricks and Sir James Black, a 1988 Nobel Prize laureate in Medicine. Efamol’s experts specifically tes- tified that the facts and data they relied on in making their determination that EPO is GRAS are of the type reasonably relied upon by experts in the field.!° All of these experts 10 The petitioners’ experts testified that, for example: EPO “satisfied the . . . scientific criteria” in establishing the safety of EPO, Declaration of Robert G. Tardiff, Ph.D., Exc. at 283-84, § 9: methods “generally recognized — 10 concluded from their review of the published scientific data, corroborated by unpublished studies, that EPO is GRAS within the meaning of 21 U.S.C. § 321(s). Exc. at 105-53. Efamol’s expert panel summarized its reasons for concluding that EPO is GRAS as follows: The necessary information to determine the safety of EPO is published in the scientific literature, and is therefore available to any scientist interested in evaluating the safety of EPO. The published literature contains information on the consumption and meta- bolism of EPO and its constituents, and contains information on the consumption of chemically related substances. The published literature contains... the most crucial animal studies performed on EPO, {which} show that EPO is not toxic or carcinogenic. The published literature also contains extensive reports of clinical studies which also support the safety of EPO. by toxicologists” were used in testing the carcinogenic potential of EPO, id at 288-89, § 17(a); “EPO has been subjected to a battery of toxicity and carcinogenicity tests consistent with that required by FDA for a new food additive,” id. at 299, § 28 (emphasis in original); “[t}he necessary information to determine the safety of EPO is published in the scientific literature,” id. at 302. 4 31; the “highly desirable procedure” of “conven[ing] an Expert Panel of qualified and experienced experts” was used in making the GRAS deter- mination for EPO, Declaration of Joseph V. Rodricks, Exc. at 397,47; FDA cntena were used “in an analysis of whether the use of [EPO] .. . can be considered as GRAS,” id. at 398-99, ¥¥ 10-11; “[t}he safety factors obtained from the dog and rat studies substanuate the safety of EPO .. .: the safety of EPO is assured beyond the level normally required by FDA.” id. at 301, € 30: experts engaged in GRAS evaluations routinely use unpublished data as part of their evaluations, Second Declaration of Joseph V. Rodricks, Exc. 1057. ¢ 16; “[f}rom a scientific standpoint, it makes no sense to disregard such published [drug study] information,” Third Declaration of Loren D. Koller, D.V.M., Ph.D., Exc. at 1042, J 16; “it is clearly apparent that documented human experience with [EPO] exists, that the data relating to this experience exceed FDA’s normal requirements to show safety and GRAS Status .. .,” Second Declaration of Joseph V. Rodricks, Exc. at 1057, § 15. Exc. at 132 (emphasis added).!! The conclusion of the expert panel that EPO is GRAS for its intended use as a dietary supplement was confirmed by Dr. Rodricks, Exc. at 394-414, and Sir James Black, M.D.. Exc at 386-93. Sir James concluded that “based on my knowledge of the scientific information and on the review of the expert panel [report on the GRAS status of EPO], I am satisfied that any scientist with the appropriate expertise and an open mind would conclude that EPO is GRAS for use as a dietary supple- ment....° Exc. at 392,416. Based on his food safety experience both at FDA and in private industry, Dr. Rodricks concluded that: [T]he necessary information to determine the safety of Evening Primrose Oil is published in the peer reviewed scientific literature, and is therefore avail able to any scientist interested in evaluating the safety of Evening Primrose Oil.... [T]he safety information available for Evening Primrose Oil far exceeds that normally required by FDA for vegetable oils such as Evening Primrose Oil. Exc. at 405, 4 21. On the misbranding issues, Efamol submitted the declara- ion of a consumer behavior expert who reviewed the labels on the seized product. The expert stated that, in his view, the labels The expert panel reviewed and analyzed 162 published articles before reaching its conclusion that EPO is GRAS. Exc. at 109 n.3 and 341-52. As directed by FDA’s regulations, 21 C.F.R. §§ 170.3(h) (1991) and 170.30(b). the panel also reviewed data from unpublished studies to corroborate the panel’s GRAS determination and to make certain that the unpublished data did not raise safety concerns about EPO. Exc. at 124-26. The panel's report establishes the panel's understanding that GRAS status according to FDA's regulations shall “ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information.” Exc. at 111, quoting 21 C.F.R. § 170.30(b); see also Exc. at 124 (“the safety and general recognition of safety of EPO are corroborated by unpublished studies”). a —— 12 > ~ would not mislead consumers.!* Efamol also submitted tes- timonial and documentary evidence that a written agreement existed between Efamol and the company to whom the bulk EPO was sent, exempting the seized EPO from the common or usual name requirement of the FDC Act, 21 U.S.C. § 343(i)(1). pursuant to FDA’s regulation, 21 C.F.R. § 101.100(d)(2) (1991). Exc. at 988-1900. The district court granted FDA’s motion for summary judgment on November 27, 1989, without addressing the burden of proof issue and, with no analysis, adopted FDA’s findings of fact verbatim. Compare FDA’s Statement of Uncontroverted Facts at @§ 12, 14, 15 and 16, Exc. at 10-11, with District Court’s Findings of Fact at §§ 12, 13, 14 and 16, A-14-15. The district court found that EPO is not GRAS because FDA’s experts did not view it as such. A-15,§ 16. The district court did not even acknowiedge Efamol’s extensive expert testimony, let alone articulate why it believed the testimony inadequate to establish a genuine issue of material fact. /d. 3. Proceedings In The Court Of Appeals. Efamol appealed to the Ninth Circuit, arguing again that FDA bears the burden of proof on the GRAS issue, and that Efamol’s expert testimony established that EPO is GRAS, or at a minimum raised a genuine issue of fact. Without analysis, the Ninth Circuit quoted one of several conflicting burden-of-proof cases and held that the burden of proving GRAS status “is placed on the proponent of the food substance in question.” Opinion at A-7 (citation omitted). The Ninth Circuit then rejected Efamol’s testimony in total, Stating that [s]cientific studies which would support a finding that EPO is generally recognized as safe must be based on 12 m Aas He stated further that no definitive conclusion on this issue could be reached without empirical data, in the form of a consumer survey, evidence which FDA did not present. Exc. at 1003-5, 99 8-13. 13 human, animal, analytical and other scientific studies. 21 C.F.R. § 170.3(h). This data must be collected and analyzed with regard to EPO’s use as a dietary sup- plement. Furthermore, the information must be generally available to the community of experts and Subjected to peer evaluation, criticism and review appropriate to establish such safety. 21 C.F.R. § 170.30(b); Weinberger v. Bentex Pharmaceuticals. Inc., 412 U.S. 645, 652 (1973). The evidence submitted by Efamol or used by Efamol’s experts to evaluate EPO fails to meet the above criteria. Some of the data considered by Efamol’s experts concerns EPO’s use as a drug and not as a dietary supplement. Other data was based on unpublished materials, which were not subjected to peer evaluation. Thus, the opinions of Efamol’s ex- perts were contaminated by their consideration of unsuitable evidence. Opinion at A-8-9 (footnote omitted). The Ninth Circuit identified two grounds for its wholesale rejection of Efamol’s expert testimony. First, the court found that the “data relied on by Efamol is insufficient under Rule 703 of the Federal Rules of Evidence.” Jd. at A-9 n.4. Second. the court cited two cases, Daubert v. Merrell Dow Pharmaceuticals. Inc., 951 F.2d 1128, 1130 (9th Cir. 1991), petition for cert. filed, No. 92-102 (July 7, 1992), and Christophersen vy. Allied-Signal Corp., 939 F.2d 1106, 1114 (Sth Cir. 1991) (en banc). cert. denied, __U.S.__, 112 S. Ct. 1280 (1992). both of which rejected expert tesumony on the basis of the test enunciated in F rye.}3 Moreover, the Ninth Circuit rejected Efamol’s expert testimony on the issue of whether labeling the seized oil “Pure Vegetable Oil” rather than “Evening Primrose Oil” was false or misleading within the meaning of 21 U.S.C. § 343(a) (1992). Opinion at A-5. The court also rejected Efamol’s evidence of a written agreement exempting the seized product from the “Common or usual name” requirement of 21 U.S.C. § 343(1)(1). Opinion at A-6-7. 14 REASONS FOR GRANTING THE WRIT A sharp conflict and much confusion exist in the circuits over the proper role and interpretation of Rule 703 of the Federal Rules of Evidence, and whether the enactment of Rule 703 eliminated the common-law Frye test. This is the fourth time in recent months that this Court has been asked to resolve the Frye issue. See note 22 infra. Many courts, including the Ninth Circuit in this case and in Daubert and the Fifth Circuit in Christophersen, are moving farther and farther away from the plain meaning of Rule 703 and are making up rules of evidence tor individual cases in an apparent attempt to resolve complex cases by excluding one party’s expert testimony, thereby dis- posing of the cases on summary judgment. This case is an extreme consequence of the restrictive approach, rejecting the kind of scientific data that all scientists, in and out of FDA, use to make food safety evaluations. 1. This Court Should Resolve The Conflict In The Circuits Over Fed. R. Evid. 703 And Frye. The controversy over Rule 703 involves whether courts “can impose an independent reasonableness standard on the expert s reliance, or whether it is enough that experts in the field customarily rely on the type of data upon which the expert intends to rely.” Michael C. McCarthy, Note, “Helpful” Or “Reasonably Reliable”? Analyzing The Expert Witness's Methodology Under Federal Rules Of Evidence 702 And 703, 77 Cornell L. Rev. 350, 356 n.34 (Jan. 1992).!4_ To complicate 14 In Japanese Elec. Prod. Antitrust Litig. v. Matsushita Elec. Indus. Co., Lid., 723 F.2d 238, 276 (3d Cir. 1983), for example, the Third Circuit reversed the trial court’s ruling that it was obliged to determine the reasonableness of the expert's reliance. The court stated that “[t]he proper inquiry [under Rule 703] is not what the court deems reliable, but what experts in the relevant discipline deem it to be.” Rev'd on other grounds sub nom., Matsushita Elec. Indus. Co., Ltd. v. Zenith Radio Corp., 475 U.S. 574 (1986). A more . Testrictive approach was taken in Jn re “Agent Orange” Prod. Liab. Litig., 611 F. Supp. 1223, 1244 (E.D.N.Y. 1985): “The more restrictive view 15 matters further, some courts — including the Ninth Circuit in this case — use the common-law Frye test, which has no textual basis in the Federal Rules of Evidence, asa ground for excluding expert testimony. Professor Imwinkelried has provided a detailed explanation of this conflict: At the time of the adoption of the Federal Rules of Evidence, the overwhelming majority of jurisdictions subscribed to the Frye standard for determining the admissibility of scientific testimony. . . . Against this backdrop, Congress enacted the Federal Rules, including rule 703. Rule 703 permits an expert to base an opinion on information only “[i]f [it is] of a type reasonably relied upon by experts in the par- ticular field.” At least one line of authority holds that by virtue of the rule’s use of the term “reasonably,” the judge may bar an expert from relying on a type of information even when it is the Customary practice within the expert’s specialty to rely on that type of data, if the judge finds that reliance objectively un- reasonable. If that interpretation of rule 703 is correct. rule 703’s application to the expert’s major premise could result in a more conservative test for admis- sibility than the Frye standard; even when the proponent of the testimony can prove generai accep- tance, the judge could second-guess the scientific community and bar the testimony.!5 As to the status of the Frye test, Justice White. dissenting from this Court’s denial of the petition for writ of certiorari of the requires the trial court to determine not only whether the data are of a type reasonably relied upon by experts in the field, but also whether the underlying data are untrustworthy for hearsay or other reasons.” Aff don other grounds, 818 F.2d 187 (2d Cir. 1987), cert. denied, 487 U.S. 1234 (1988). 'S Edward J. Imwinkelried, The “Bases” Of Expert Testimony: The Syllogistic Structure Of Scientific Testimony, 67 N.C.L. Rev. 1, 18-19 (Nov. 1988) (citations omitted) (foomotes omitted). if Fifth Circuit's decision in Christophersen v. Allied-Signal (orp, Summarized the division in the courts As the Fifth Circuit is divided, so the Courts of Appeals are in disagreement. Some continue to apply the approach set forth in Frye in deciding whether expert evidence 1s admissible. F.g., Daubert v. Mer rell Dow Pharmaceuticals, Inc., 951 F.2d 1128 (CA9 1991): United States v. Two Bulls, 918 F.2d 56 (CA® 1990): United States v. Smith, 869 F.2d 348 (CA7 1989). But courts in other circuits have concluded that Frve was superseded in 1975 by the Federal Rules of Evidence, which they maintain established a lower threshold for determining the admissibility of expert evidence. F£.g.. United States v. Jakobetz, 60 U.S.L.W. 2470, ___ F.2d (CA2 1992); DeLuca v. Merrell Dow Pharmaceuticals, inc., 911 F.2d 941 (CA3 1990). Because this is an important and recurring issue, | would grant certiorari to resolve the conflict. Christophersen v. Allied-Signal Corp., 112 S. Ct. at 12%1 (1992) (White & Blackmun, J.J., dissenting from denial of certiorari). As early as 1986, two Justices indicated the need for granting ceruoran to resolve the circuit split over Frye. Mustafa v. United States, 479 U.S. 953, 953 (1986) (White & Brennan, J.J., dissenting from denial of certiorari) (““] would grant certiorari to resolve the conflict on an obviously recurring and important issue,”’),16 the circuits on the admissibility of expert tesumony under Rules 702 and 703 and the continuing questions regarding Frye’ s viability in light of the Federal Rules... . {t]he ume may be npe for the Supreme Court to grant certiorari on these issues.”); Gary Taylor, Expert Witness Opinion Eyed; Circuits Split on Issue, Nat | LJ., at 3-4 (Oct. 21, 1991) (*Tnal Lawyers for Public Justice Says that the [Christophersen) opinion places the 5th Circuit at odds with the 3d Circuit on the expert witness issue, and only the high court can sort things i ee 3 17 a. The split in the circuits over Fed. R. Evid. 703 and the Frye test. Some courts of appeals properly interpret the expert tes timony provisions of the Federal Rules of Evidence and recog nize that Rule 703 is not a tool for judges to weigh conflicting expert testumony. These same courts also recognize that the Frye test has been superseded by the Federal Rules of Evidence.!’ The Third Circuit has provided particularly help ful commentary in this area. In United States v. Downing, 753 F.2d at 1232-37, the court surveyed the history of Frye’'s serious flaws,” notably “its vagueness and its conservatism and concluded that Frye “should be rejected as an independent controlling standard of admissibility” because it “reflects a conservative approach to the admissibility of scientific evidence that 1s at odds with the spirit, if not the precise language, of the Federal Rules of Evidence.” /d. at 1236-37. In DeLuca Merrell Dow Pharmaceuticals, Inc., 911 F.2d 941 (3d Cir 1990), the Third Circuit also recognized that Rule 703 is satisfied once there is a showing that an expert s testimony 1s based on the type of data a reasonable expert in the field would use in rendering an opinion on the subject at issue; it does not address \S2e2" ) FIRST CIRCUIT: Int’! Adhesive Coating Co., In Boltan Emerson In Inc., 851 F.2d 540, 544-45 (ist Cir. 1988) (“As noted in Rule 703 reasonableness is measured against the facts or data upon which experts in the particular field normally rely When the factual underpinning of an expert s opinion is weak, it is a matter affecting the weight and credibility of the tesumony — a question to be resolved by the jury.”) (citations omitted) SECOND CIRCUIT: United States v. Jakobetz, 955 F.2d 786, 794 (2d Cir 1992) (“[T]he Frye standard [has] been superseded by the Federal Rules of Evidence, which stress{es] a permissive method for determining admis- sibility.”), petition for cert. filed, No. 91-7921 (April 8, 1992). THIRD CIRCUIT: United States v. Downing, 753 F.2d 1224, 1237 (3d Cir 1985) 18 the reliability or general acceptance of an expert's methodology. Id. at 953. summary judgment granted on remand, No. 87-226 (GEB), 1992 U.S. Dist. LEXIS 6511 (D.N.J. April 29, 1992). Some circuits have also refused to use Rule 703 as a vehicle for judges to take away the jury function of weighing expert testimony.!* Yet strangely these same circuits insist on con- tinuing to apply the Frye test.. See note 21 infra. 1S ‘ See: FOURTH CIRCUIT: ClinchfieldR R. Co. v. Lynch, 784 F.2d 545, §54 (4th Cir. 1986) (“[I}t is better to admit relevant scientific evidence in the same manner as other expert tesumony and allow its weight to be attacked by cross examinauion and refutation.) (citation omitted). SIXTH CIRCUIT: Mannino v. Int'l Mfg. Co., 650 F.2d 846, 853 (6th Cir. 1981) (2Great liberality is allowed the expert in determining the basis of his opinions under Rule 703. Whether an opinion should be accepted is not for the tnal judge.”). SEVENTH CIRCUIT: United States v. Tranowski, 659 F.2d 750, 755 n.10 (7th Cir. 1981) (“Rule 703 permits a court to admit an expert opinion based on hearsay, if reliance on such factual bases is ure normal practice of experts in the field in reaching their conclusions.”) (emphasis added), rev'd on other grounds, 702 F.2d 668 (1983), cert. denied, 468 U.S. 1217 (1984). EIGHTH CIRCUIT: United States y. Kail, 804 F.2d 441, 448 (8th Cir. 1986) (“[Q]juestions as to the reliability of the experts’ judgments go to the weight to be given . . . to the testimony, and not toe the admissibility of the tesumony. We therefore conclude that the district court did not err in admitung the expert testumony to the jury under Rule 703.”). NINTH CIRCUIT: Rogers v. Raymark Indus., Inc., 922 F.2d 1426, 1429- 30 (9th Cir. 1991) (“an expert opinion may be based on any type of evidence commonly used by experts in the field.”) (citation omitted). D.C. CIRCUIT: Ambrosini v. Labarraque, No. 90-7146 and No. 90-7148, slip op. at 5 (D.C. Cir. June 12, 1992) (“Rule 703 broadens the acceptable bases for expert tesumony by allowing an expert to base an opinion on hearsay and other evidence not admissible in court.”). 19 In other circuits, however, a “disturbing trend” exists for reading Rule 703 very restrictively and excluding evidence under that rule. McCarthy, supra page 14, at 366 n.96. This trend arose out of Judge Weinstein’s opinion in In re “Agent Orange,” 611 F. Supp. 1223.'? As one commentator noted, ‘“[w]hen the Court is unconvinced. it grants defendants’ motions for summary judgment. Rather rare before Weinstein’s [/n re Agent Orange] decision, this movement is gathering momen- tum."” McCarthy, supra page 14, at 367 n.96.2° The Ninth Circuit in this case cited Daubert, 951 F.2d at 1130, and Christophersen, 939 F.2d at 1114, in its holding that Efamol’s expert opinions were “contaminated.” Opinion at A-9. These Fifth and Ninth Circuit opinions are representative of two of the eight circuits that have employed a restrictive reading of Rule 703 and/or have invoked the Frye test to exclude expert testimony.*! “Whatever degree of clarity the Third 19 In In re “Agent Orange,” the court decided not to allow the cases of almost 300 individuals who had opted out of a class settlement to survive summary judgment. The decision hinged on a restrictive reading of Rule 702 and a finding that the plaintiffs’ expert testimony was inadmissible under both Federal Rules of Evidence 703 and 403. 611 F. Supp. at 1256. 20 For an extended iliustration of cases in which courts have used Rule 703 as a basis for granting summary judgment, see McCarthy supra page 14, at 358 nn.41-42. 21 See: FOURTH CIRCUIT: Ellis v. Int'l Playtex, inc., 745 F.2d 292. 304 n.15 (4th Cir. 1984) (“Although this court has expressed concern over the Frye rule, we have continued to recognize its validity in certain circumstances.”). SIXTH CIRCUIT: United States v. Metzger, 778 F.2d 1195. 1203 (6th Cir. 1985) (“[a]lthough ‘[a] number of the federal courts have responded to the enactment of Rule 702 by rejecting the Frye standard, [this circuit] still predicate[s] the admission of scientific evidence on general acceptance in the community’) (citations omitted), cert. denied, 477 U.S. 906 (1986). SEVENTH CIRCUIT: United States v. Smith, 869 F.2d 348, 351 (7th Cir. 1989) (“[T]his circuit has continued to affirm (and to apply) the Frye standard.”). —————————— 20 Circuit brought to Rule[] . . . 703 in DeLuca was shattered by the Fitth Circuit’s most recent pronouncements on scientific expert testimony in Christophersen...” McCarthy, supra page ld. at 381. In Christophersen, the district court struck the plaintiff’ s expert's testimony “as it is not based upon the type of evidence usually relied upon by experts in the field of cancer research.” Christophersen, No. W-88-CA-098, slip op. (W.D. Tex. Ox tober 12, 1989), reprinted in Petition for Writ of Certiorari at A74, No. 91-785 (filed November 12, 1991). Summary judg ment was issued for the defendants. The Fifth Circuit voted en banc to affirm the judgment of the district court, stating that “the inquiry into the . . . ‘facts and data’ underlying an expert's tesumony is not limited to the admissibility of that data,” but extends to the sufficiency and accuracy of underlying facts. 939 F.2d at 1114. The Frye test, the court explained, requires a court to determine “whether the methodology or reasoning that the expert uses to connect the facts to his conclusions is generally accepted within the relevant scientific community.” /d. at 1115. The court in Daubert affirmed a summary judgment ruling with similar reliance on the Frye test. The court stated: Expert opinion based on a scientific technique “‘is admissible if it is generally accepted as a reliable technique among the scientific community.” United States v. Solomon, 753 F.2d 1522, 1526 (9th Cir. EIGHTH CIRCUIT: United States v. Two Bulls, 918 F.2d 56, 60 n.7 (8th Cir. 1990) (Federal Rules of Evidence do not supersede Frye.). TENTH CIRCUIT: Head v. Lithonia Corp., Inc., 881 F.2d 941, 944 (10th Cir. 1989) (“Because the record does not sufficiently establish the trustwor- thiness of topographical brain mapping or its acceptance in the relevant scientific community” court vacated the judgment and remanded for a new trial.). D.C. CIRCUIT: Kropinski v. World Plan Executive Council - U.S., 853 F.2d 948, 956-57 (D.C. Cir. 1988) (expert opinion was excluded because it did not have a “significant following in the scientific community, let alone general acceptance.”). i 1985) (citing Frye v. United States, 293 F. 1013. 1014 (D.C. Cir. 1923) YS1 F.2d at 1129-31 (citing Christophersen, 939 F.2d at 1109). In Daubert and now in this case, the Ninth Circuit has refused to join the circuits that recognize that the Frye test has been displaced by the Federal Rules of Evidence. Certiorari was recently sought in Christophersen and Daubert to resolve the Frye issue. Jakobetz is the other petition for certiorari.“* In response to that petition, Solicitor General Kenneth W. Starr acknowledged that the courts of appeals are divided over whether Frye is still good law.2? The Solicitor General argued however, that Jakobetz “is not an appropriate case in which to resolve the issue in which the courts of appeals are in conflict.’ Id. at 12.4 In contrast, this case is a particularly appropriate one for the Court to resolve the conflict and confusion over Rule 703 and the Frye test. This case turns squarely on whether the Ninth See United States v. Jakobetz, 955 F.2d 786 (2d Cir. 1991). Petition for Wnit of Certiorari (pending), No. 91-7921 (filed April 6, 1992) (petition seeks review of the Second Circuit's refusal to follow other circuits in requiring prosecutors to meet Frye’s heightened standard for admissibility when seeking to introduce new forms of forensic evidence): Daubert y Merrell Dow Pharmaceuticals, Inc., Petition for Writ of Certiorari | pending) No. 92-102 at 9-10 (filed July 7, 1992) (petition requested that this Court resolve whether the judge-made rule of Frye “was eliminated as a ground for excluding evidence by Congress’s enactment of uniform Federal Rules of Evidence.”). See also Christophersen v. Allied Signal Corp., Petition for Wnt of Certiorari, No. 91-785 at 20 (filed November 7, 1991. denied March 2. 1992) (certiorari petition requested the Court's prompt intervention to resolve the Frye issue). 732 ~ Jakobetz v. United States, Brief For The United States In Opposition (To The Petition For Wnit Of Certiorari], No. 91-7921 (filed June 10. 1992) at 8-10. *4 The issue in Jakobetz is whether DNA profiling is admissible under the Federal Rules of Evidence. According to the Solicitor General. the DNA profiling technique is admissible even under the restrictive Frye test. /d. iii ieee %9 ht hw Circuit applied the correct test under Rule 703, and whether the outdated Frye rule should have been invoked in assessing Efamol’s expert testimony. Moreover, this Court’s review is necessary to address Christophersen, which “breathes new life into the Frye rule and counters ‘the movement away from the general acceptance test’” of Rule 703.29 The fact that another circuit — the Ninth Circuit— has now boarded the Christopher- sen bandwagon in two recent decisions only heightens the conflict and confusion in the federal courts over the admis- sibility of expert testimony under Rule 703 and whether Frye is still good law. If this Court grants review of Daubert and/or Jakobetz, it should also grant review of the instant petition or hold it pending disposition of the other(s). Even if this Court denies review of Daubert and Jakobetz, it should grant this petition because, unlike the Daubert and Jakobetz petitions, the instant petition also presents the opportunity for this Court to resolve the conflict and confusion in the circuits over Rule 703 of the Federal Rules of Evidence. b. The test that should be used by the courts. The Ninth Circuit’s decision in this case illustrates how far federal courts are diverging from Rule 703. Having decided Daubert, the Ninth Circuit cited that decision and Christopher- sen to reject more than 300 pages of detailed scientific tes- timony. Congress plainly intended through the adoption in 1975 of the Federal Rules to liberalize the admissibility of expert testimony, thereby eliminating the common-law Frye test.?° The Ninth Circuit shuts the door that Congress attempted to open — in this case, with the spectacular result of denying useful Recent Case, 105 Harv. L. Rev. 791, 794-95 (1992) (citation omitted). 26 The Advisory Committee’s note to Rule 703 provides specifically that “[t]he rule is designed to broaden the basis for expert opinions beyond that current in many jurisdictions and to bring the judicial practice into line with the practice of experts themselves when not in court.” See also Faust F. Rossi, Modern Evidence and the Expert Witness, 12 Litig. 18, 18 (Fall 23 evidence routinely used by experts, even those within FDA, to make GRAS determinations. The Supreme Court should define the proper test under Fed. R. Evid. 703. This Court should clarify that “[t]he proper inquiry [under Rule 703] is not what the court deems reliable. but what experts in the relevant discipline deem it to be... . [I]f an expert avers that his testimony is based upon data in the field that experts rely upon, then Rule 703’s requirements are generally satisfied.”?7 This Court should also make clear that the common-law Frye test has been displaced by the Federal Rules of Evidence.28 As this Court has emphasized, “[b]Jecause the Federal Rules of Evidence are a legislative enactment, we turn to the ‘traditional tools of statutory construction,’ in crder to construe their provisions.” Beech Aircraft Corp. v. Rainey, 488 U.S. 153, 163 (1988) (citation omitted). Citing Beech Aircraft, then-Judge 1985) (“The welcome mat was rolled out in 1975, when Congress enacted Federal Evidence Rules 702 through 705. These four provisions, comprising only six sentences, confirmed the judicial trend toward expanded admis- sibility of expert testimony.”) *7 DeLuca, 911 F.2d at 952 (citations omitted). See also Mannino, 650 F.2d at 851 (“[t]he purpose of Rule 703 is to make available to the expert all of the kinds of things that an expert would normally rely upon in forming an opinion, without requiring that these be admissible in evidence”: through it “the law is catching up with the realities of professional life.”): Clinchfield R.R. Co., 784 F.2d at 553-54 (Rule 703 satisfied with a showing that data are “reasonably relied upon by experts in the particular field” — questions going to weight should be “attacked by cross examination and refutation.”) (cita- tions omitted). 28 See 3 Jack B. Weinstein & Margaret A. Berger, Weinstein’ s Evidence § 703[01), at 702-36 (1991) (“Elimination of the Frye test is consistent with the underlying policy of Article VII” of the Federal Rules of Evidence) (footnote omitted); 22 C. Wright & K. Graham, Federal Practice and Procedure § 5169, at 108 (1978) (Frye did not survive the enactment of the Federal Rules of Evidence). 24 (now Justice) Thomas emphasized that on evidence questions a court must “begin as... with any statute, with the language of the rules themselves.” United States v. Rogers, 918 F.2d 207. 209 (D.C. Cir. 1990). Furthermore, in a decision citing an opinion issued by then-Judge (now Justice) Kennedy. the Ninth Circuit recog nized that the Federal Rules of Evidence “supersede the rules of evidence based on common-law principles,” and that “the courts are not free to establish rules of evidence independent of the Federal Rules.” United States y. Grajeda, 570 F.2d 872. 874 (9th Cir. 1978) (citing United States v. Dixon. 547 F.2d 1079, 1082 (9th Cir. 1976) (Kennedy, J.) (footnote omitted), Grajeda, 570 F.2d 872, withdrawn and new opinion issued on alternate ground, 587 F.2d 1017 (9th Cir. 1978). Although the Ninth Circuit has chosen to ignore Justice Kennedy’s opinion, his view was endorsed by this Court, which recognized that “[bJefore the present Rules were promulgated, the admissibility of evidence in the federal courts was governed in part by statutes or Rules, and in part by case law.” The Court then agreed that “in principle, under the Federal Rules no common law of evidence remains.” United States v. Abel, 469 U.S. 45. 50-52 (1984) (citations omitted). The Frye test appears nowhere in the text of the Federal Rules of Evidence. As such, this common-law rule of evidence no longer remains. The Senate Report accompanying the Federal Rules of Evidence cited the need for “a comprehensive code of evidence intended to govern the admissibility of proof in all trials before the Federal courts beeause of the lack of uniformity and clarity in the present law of evidence on the Federal level.” S. Rep. No. 93-1277, 93d Cong., 2d Sess. (1974), reprinted in 1974 U.S. Code Cong. & Admin. News 7054. In order to maintain a uniform rule of evidence, this Court Should make clear that Frye is no longer good law. Roughly one-third of all cases in federal courts depend on expert testimony.*? Professor Imwinkelried summarized why Frye presents a “formidable” and unreasonable barrier in cases involving such testimony: Even if the world’s leading scientific authority on a subject attests to a new theory, even if the Nobel prize winner in a specific field conducts a thorough. wel] designed experiment to validate the technique, the courts Cannot admit the evidence until most of the scientists in that specialized field know and approve the theory.” The same logic applies to Rule 703. Courts should not substitute their judgment for the judgment of experts 2. The Supreme Court Should Resolve The Conflict As To Which Party Bears The Burden Of Proof On The Issue Of GRAS Status. This case presents a second conflict among the circuits Whether FDA or the manufacturers of food products bear the burden of proving GRAS status in a seizure action. This is an issue of fundamental importance to the food industry. Inde- pendently determining that a food ingredient is GRAS and marketing it without undergoing the lengthy delays of the FDA food additive approval process is a major route by which food ingredients come to the market. See 21 C.F.R. § 182. 1(a). After rejecting all of Efamol’s testimony on the GRAS issue, the Ninth Circuit held that summary judgment was ap- propriate because “Efamol failed to make a showing sufficient to establish the existence of an element essential to its case. and ey Imwinkelried, supra page 15, at | 30 Edward J. Imwinkelreid, The Standard For Admitting Scientific Evidence: A Critique From The Perspective Of Juror Psychology, 28 Vill. L. Rev. 554, 557 (1982-83) (footnote omitted). 26 on which it bears the burden of proof at trial.” Opinion at A-9,3! As the basis for this crucial allocation of the burden of proof, the Ninth Circuit quoted dictum in United States v. An Article of Food . . . Coco Rico, 752 F.2d 11, 15 (1st Cir. 1985) and, without analysis of the issue, placed the burden of proof of GRAS status on Efamol. Opinion at A-7, 9. The FDC Act authorizes the government to proceed against adulterated or misbranded products on libel of information in any federal district court. 21 U.S.C. § 334(a) (1992). The FDC Act contains numerous grounds upon which a food can be deemed to be adulterated or misbranded.32 It is clear that in all enforcement actions under the FDC Act for adulteracion or misbranding, FDA must prove each element of its case by a preponderance of the evidence.33 In this case, however. the Ninth Circuit heid that the burden is different where FDA seizes a food product alleging that it is not GRAS and is therefore an unapproved food additive. Had Congress intended to make the The Ninth Circuit also erred because Efamol was only required to show a genuine issue of material fact to be entitled to a trial. Efamol was not required to prove that it would prevail at trial to overcome a motion for summary judgment. Anderson v. Liberty Lobby, Inc., 477 U.S. 242. 248-49 (1986). 2 For example, a food may be deemed “adulterated” if it “contains any poisonous or deleterious substance which may render it injurious to health,” or “if it consists . . . of any filthy, putrid, or decomposed substance. . . .” 21 U.S.C. § 342(a)(1), (3) (1992). A food may be deemed “misbranded” under the FDC Act if, for example, “its labeling is false or misleading in any particular, . . .” or if “it is offered for sale under the name of another food.” 21 U.S.C. § 343(a)(1), (b) (1992). Nat'l Labor Relations Bd. v. Transport Management Corp., 462 U.S. 393, 401 (1983) (government carries the burden of proving the elements of a4 Statutory violation). See also United States v. General Foods Corp 446 F. Supp. 740, 753 (N.D.N.Y.), aff'd, 591 F.2d 1332 (2d Cir. 1978); United States v. 119 Cases, More or Less .. . “New Dextra Brand Fortified Cane Sugar * * *,” 231 F. Supp. 551, 558 (S.D. Fla. 1963). aff d per curiam, 334 F.2d 238 (Sth Cir. 1964); United States v. 46 Cases. More or Less . “Welch's Nut Carameis * * *,” 204 F. Supp. 321, 322 (D.R.I. 1962) 27 burden different in GRAS cases, it would have made its intent clear. Cf. United States v. 88 Cases, More or Less, .. . Bireley’s Orange Beverage, 187 F.2d 967 (3d Cir.), cert. denied, 342 U.S. 861 (1951). There is nothing in the language of the statute that even suggests there is a different burden of proof when a seizure action is brought under 21 U.S.C. § 342(a)(2)(C), as opposed to any other subsection of § 342. The legislative history is unequivocal that Congress in- tended, consistent with all other FDC Act enforcement actions, that FDA bear the burden of proving that a substance is not GRAS. The Food Additives Amendment of 1958 added the term “food additive” to the FDC Act, 21 U.S.C. § 321(s). The Department of Health, Education, and Welfare (now the Depart- ment of Health and Human Services, of which FDA is a part) issued a statement that all of the various bills contain a “generally recognized” clause in one form or another .... It is important to note that under all the bills, as drawn, the burden would be on the Government, in an enforcement proceeding, to prove that a substance is not generally recognized by experts as safe and is therefore within the scope of the bill.54 The chief counsel of FDA at the time agreed: We have the burden, no matter how this bill goes, of proving that a product is not generally recognized as safe among experts in the courts. Let us assume that this bill came out as we recommended it and company X had a chemical which had not been adequately tested, we thought it was not generally recognized as safe, the applicant thought it was generally recognized as safe. We would have the burden of going to court 34 Food Additives: Hearings Before a Subcomm. of the House Comm. on Interstate and Foreign Commerce, 85th Cong., 2d Sess. 455 (1958) (supplemental statement of the Department of Health, Education, and Welfare’s views to accompany the statement of George P. Larrick, FDA Commissioner) (emphasis added). . 28 was not generally recognized as safe.35 These contemporaneous interpretations of the statute by those charged with its enforcement are entitled to great deference. See, e.g., Udall v. Tallman, 380 U.S. 1, 16 (1965): Zuber v. Allen, 396 U.S. 168, 192-93 (1969). The district court and the Ninth Circuit ignored this legislative history. The circuits are split on the issue of who bears the burden of proof on the GRAS issue. Without much discussion. some circuits have required FDA to prove that a substance is not GRAS. United States v. An Article of Food . . . 345/50-Pound Bags, 622 F.2d 768, 771 (Sth Cir. 1980)(“‘the government had the burden of demonstrating that no genuine issue of material fact existed” as to general recognition of safety): United States v. Articles of Food and Drug .. . Coli-Trol, 518 F.2d 743. 746 (Sth Cir. 1975)(FDA bears burden of proof on the GRAS issue): United States v. Ewig Bros. Co., Inc., 502 F.2d 715, 719 (7th Cir. 1974)(the government “need only prove that ‘such sub- stance is not generally recognized . . . to be safe under .. .’ 21 U.S.C. § 321(s)”) (footmote omitted), cert. denied. 420 U.S. 945 (1975).36 Other courts of appeals appear to place the burden on the manufacturer to prove GRAS status.37_ None of these cases. Chemical Additives in Foods: Hearings Before a Subcomm. of the House Comm. on Interstate and Foreign Commerce. 84th Cong., 2d Sess. 226 (1956) (statement of Mr. William W. Goodrich) (emphasis added). On the similar question of general recognition of safety and efficacy of drugs, courts have stated that the government has the burden of proof. United States v. Alcon Lab., 636 F.2d 876, 888 (1st Cir.), cert. denied, 451 U.S. 1017 (1981); United States v. Articles of Food and Drug ... Coli-Trol, 372 F. Supp. 915, 917 (N.D. Ga. 1974), aff d, 518 F.2d 743 (5th @ir. 1975); United States v. An Article of Drug ... “Bentex Ulcerine,” 469 F.2d 875, 878-79 (5th Cir. 1972), cert. denied, 412 U.S. 938 (1973). *T An Article of Food . . . Coco Rico, 752 F.2d at 15 (Ist Cir, 1985): F mali Herb, Inc. v. Heckler, 715 F.2d 1385. 1390-91 (9th Cir. 1983): United 29 however, focused on the burden of proof issue because it was not central to the decision. The court in Coco Rico, on whose dictum the Ninth Circuit chose to rely, appears to have confused the burden of proving GRAS status, which Congress placed on FDA, with the burden of proving safety for a food additive when one seeks FDA approval to market the additive. In the latter case Congress clearly put the burden of proving safety on the proponent of the food additive. 21 U.S.C. § 348. The Ninth Circuit’s decision dramatically alters the playing field by erroneously shifting the burden of proof. The Ninth Circuit said that Efamol’s failure to meet the burden of proof on the GRAS issue warranted summary judgment. Therefore, the Ninth Circuit’s misallocation of the burden of proof by itself warrants the grant of certiorari in this case. 3. Efamol’s Evidence On The Misbranding Issues Raises Genuine Issues Of Fact Requiring A Trial. The Ninth Circuit’s holding on the misbranding issues is based on a misreading of Dr. Ross’ testimony, which clearly raises a genuine issue of fact as to whether the descriptor “Pure Vegetable Oil” on drums of oil is misleading,*® and a misread- ing of the documents Efamol submitted to support its claim of an exemption under 21 C.F.R. § 101.100(d)(2) from the ““com- mon or usual name” requirement of 21 U.S.C. § 343(i).39 States v. An Article of Food . .. FoodScience Lab., Inc., 678 F.2d 735, 739 (9th Cir. 1982). * The Ninth Circuit rejected Dr. Ross’ testimony because it claimed he “based his opinion on the encapsulated version of EPO.” Opinion at A-5. Dr. Ivan Ross’ declaration demonstrates just the opposite; his opinion was based on the labels on the seized drums. Exc. at 1003-5, 9§ 9-13. In Dr. Ross’ opinion, whether the labels on the seized products are misleading cannot be determined without a consumer survey, which FDA did not produce. Exc. at 1005, 4 13. FDA therefore failed to meet its burden. 3 . ‘. . . . *° ‘There is no disagreement that the intent of this regulation, to assure that processing of the bulk oil does not result in adulteration or misbranding, 30 The misbranding issues are unimportant, as contrasted to the others in the case. Efamol has repeatedly stated its willingness to stipulate to relabeling of the seized product as contemplated under 21 U.S.C. § 334(d) to dispose of these issues. CONCLUSION For the foregoing reasons, certiorari should be granted. Respectfully submitted, JAMES R. PHELPS Counsel of Record Hyman, Phelps & McNamara, P.C. 700 Thirteenth Street, N.W. Suite 1200 ‘ Washington, D.C. 20005 (202) 737-5600 July 28, 1992 was met. The aocuments on which Efamol relies to establish an agreement, Exc. at 994-1000, do not raise “unresolved questions,” Opinion at A-6, but Clearly resolve questions necessary for further processing, as contemplated by 21 C.F.R. § 101.100(d)(2). At a minimum. these documents raise a genuine issue of material fact requiring a trial. APPENDIX i A-i TABLE OF CONTENTS Page Ninth Circuit Opinions and Orders (No. 90-55086): Opinion and Order filed April7,1992 ..... A-] Order filed June 12,1992 ............ A-11 Order filed June 29,1992 ............ A-12 District Court Opinions and Orders (No. CV 89-73 MRP): Findings of Fact and Conclusions of Law filed November 27,1989 ........ A-13 Order and Judgment filed POET 21, Eee wk ee A-17 eh Gls BD ake eee ee ee ee A-18 ai Usk. Sema emege) tk cs és oY A-19 21 U.S.C. § 343(a)(1) and(@)Q1) . 2 ee ee A-20 A ae Se oh A-2] oe se NS) fk ee ak eee - A-22 PA ee Pee ee ee ee eee A-23 55 Fed. Reg. 10,932 (March 23,1990) ........ A-24 55 Fed. Reg. 6384 (February 23,1990) ....... A-4] 48 Fed. Reg. 5716 (February 8, 1983) ........ A-71 . 48 Fed. Reg. 239 (January 4,1983) ......... A-86 F 43 Fed. Reg. 31,349 (July 21,1978) ......... A-93 4 43 Fed. Reg. 14,064 (April 4, 1978) ......... A-107 : 42 Fed. Reg. 41,876 (August 19,1977) ....... A-125 42 Fed. Reg. 38,609 (July 29,1977) ......... A-138 A-1 FOR PUBLICATION United States Court Of Appeals FOR THE NINTH CIRCUIT UNITED STATES OF AMERICA, Plaintiff-Appellee, v. 45/194 KG. DRUMS OF PURE VEGETABLE OIL, et al., Defendant, EFAMOL, LTD. Claimant-Appellant. No. 90-55086 D.C. No. CV-89-0073-MRP OPINION | Appeal from the United States District Court for the Centra! District of California Mariana R. Pfaelzer, District Judge, Presiding Argued and Submitted April 5, 1991—Pasadena, California Filed April 7, 1992 Before: Alex Kozinski and Diarmuid F. O’Scannlain, Circuit Judges, and Stephen M. McNamee,” District Judge. Opinion by District Judge McNamee The Honorable Stephen M. McNamee, United States District Judge for the District of Arizona, sitting by designation. A-2 ‘ SUMMARY Health and Safety Affirming a district court grant of summary judgment, the court of appeals held that the labeling of bulk EPO (evening primrose oil) as “Pure Vegetable Oil” is misbranding under 2] U.S.C. § 343. Appellant Efamol, Ltd. engaged in the export to the United States of evening primrose oil (EPO). Efamol sold EPO as a dietary supplement of fatty acids. Despite Efamol’s assertion that it would not export EPO to the U.S.. it put the mixture into soft gelatin capsules for shipment to this country in barrels labeled ‘‘Pure Vegetable Oil.” A U.S. Marshall [sic] seized the oil. The district court held that EPO Was misbranded and was an unsafe food additive in violation of federal law. The district court granted summary judgment for the government on its forfeiture action. [1] The facts in this case failed to support Efamol’s argu- ment tl. t labeling the bulk EPO as “Pure Vegetable Oil” was not misbranding within the meaning of 21 U.S.C. § 343, [2] The record showed that the condemned substance was commonly sold and referred to as “evening primrose oil” or “oil of evening primrose” and not “pure vegetable oil.” [3] In addition, Efamol had no simple, concise document Satisfying the exemption requirements of 21 C.FR. § 101.100(d)(2). [4] Rather than indicatiig an express intent to package the EPO capsules in a particular manner and ensure their purity, the documents revealed nothing more than a series of negotiations for the encapsulation of EPO. [5] No regulatory approval existed for the sale of EPO as a “food additive.” [6] Thus. summary judgment was appropriate because Efamol failed to make a showing sufficient to establish the existence of an element essential to its case, and on which it bears the burden of proof at trial. A-3 COUNSEL James R. Phelps, Hyman, Phelps & McNamara, | ee Washington, D.C., for the claimant-appellant. Mary K. Pendergast, Associate Chief Counsel, Food and Drug Administration, Rockville, Maryland, for the plaintiff-appellee. OPINION McNAMEE, District Judge: FACTS Appellant, Efamo] Ltd., Surrey, England, researches, ex- ports and markets evening primrose oil (EPO). EPO is made from the crushed seeds of the evening primrose plant. Efamol sells EPO as a dietary supplement of fatty acids. In February 1979, the Food and Drug Administration (FDA) informed Efamol representatives that EPO was not generally recognized as safe for use as a dietary supplement. If Efamol wanted to export EPO to the United States, it would have to file a Food Additive Petition with the FDA, pursuant to 21 C.F.R. section 171, or an affirmation petition in accordance with 21 C.F.R. section 170.35. Efamol informed the FDA it would no longer export EPO to the United States. ! Despite Efamol’s assertion that it would not export EPO to the United States, Efamol has been shipping bulk EPO from the United Kingdom to Banner Gelatin Products (Banner) in In 1985 the FDA issued Import Alert 66-04 for Evening Primrose Oil. The FDA revised the alert in June 1985. The alert instructs FDA officials to detain evening primrose oil labeled for food use because the agency considers it an unsafe food additive. However, Alert 66-04 provides that the oil may be sold as a food or drug if: (1) when sold as a drug, it is considered a new drug and the responsible person hold{s] an approved new drug application or (2) when sold as a food, it is considered a food additive, and prior to marketing a food additive petition is submitted to FDA in accordance with 21 C.F.R. sections 170.35 and 17i.1 and is approved by the FDA. Efamol did not submit a new drug application or a food additive petition to the FDA. A-4 Chatsworth, California since 1985. Banner mixes EPO with vitamin-E and puts the combined mixture into soft gelatin capsules. The capsules are then shipped to distributors, who market them as a dietary supplement. On January 6, 1989, the FDA filed a Complaint for Forfei- ture under 21 U.S.C. section 334(a)(1). seeking the seizure and condemnation of forty-five barrels of EPO, labeled “PURE VEGETABLE OIL.” Pursuant to a district court order the United States Marshal seized the oil on January 31, 1989. The parties filed cross motions for summary judgment. The district court granted the government’s motion for summary judgment, finding: (1) EPO was misbranded under 21 U.S.C. section 343; and (2) EPO is an unsafe food additive pursuant to 21 U.S.C. section 321. Efamol appeals the district court’s decision. For the reasons set forth below we affirm the district court's decision. I. We review the granting of a motion for summary judgment de novo. Jung v. FMC Corp., 755 F.2d 708, 710 (9th Cir. 1985). Summary judgment is appropriate when there is no genuine issue of any material fact and the moving party is entitled to judgment as a matter of law. Fed. R. Civ. P. 56(c): Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 250 (1986). When a party “fails to make a showing sufficient to establish the existence of an element essential to that party’s case, and on which that party will bear the burden of proof at trial,” Summary judgment is appropriate. Celotex Corp. v. Catrett, 477 U.S. 317, 322 (1986). I. [1] Food shall be deemed misbranded unless its label ee the “common or usual name” of the product. 21 U.S.C. § 343( It is not iuecessary to show that anyone was actually das or deceived, or that there was any intent to deceive. “The statute . Gs A-5 condemn{[s] every statement, design and device which may mislead or deceive.” United States v. 95 Barrels-Cider Vinegar, 265 U.S. 438[,] 442-43 (1924). The facts fail to support Efamol’s argument that labeling the bulk EPO as “Pure Vegetable Oil” was not misbranding within the meaning of section 343. [2] Efamol sold the oil using the name “evening primrose oil,” and Efamol’s documents, advertising and expert witnesses all referred to the substance as “evening primrose oil.” Thus, the record shows that the condemned substance was commonly sold and referred to as “evening primrose oil” or “oil of evening primrose” and not “pure vegetable oil.” in granting the government’s motion for summary judg- ment, the district court also relied on the testimony of the government's expert witness, Dr. Kassarjian. Dr. Kassarjian testified that labeling the drums of oil as “PURE VEGETABLE OIL” implied that the oil was for cooking or salads, and not part of a dietary supplement. Efamol’s expert, Dr. Ross, stated that [the] labels were not misleading because it was extremely un- likely that a reasonable consumer who saw gelatin capsules, labeled or not, would assume the product was intended as a cooking or salad oil. Plainly, Dr. Ross based his opinion on the encapsulated version of EPO. Such testimony ignores the facts presented in this case. The government is alleging that the oil as seized was misbranded. It is undisputed that when the oil was seized, it was in its bulk form. Thus, Dr. Ross’ testimony does not raise a genuine issue of material fact on the misbranding issue presented in this case and the district court properly disregarded his testimony.? > - We also consider the extent to which the label fails to reveal facts material in light of Efamol’s representations. 21 U.S.C. § 321(n). Conse- quently we find it important that the FDA had issued an import alert for EPO. The FDA cannot accurately track EPO labelled as “pure vegetable oil.” A-6 Efamol contends that even if EPO was misbranded, it is exempt from the labelling requirements under 21 C.F.R. section 101.100(d)(2). This regulation exempts manufacturers from labeling their products with the usual or common name when the food is being shipped to another area for processing, repack- aging and labeling if a written agreement exists: (1) between the shipper and the establishment that covers the shipment; (2) is signed by both parties; (3) contains the post office address of both parties; and (4) sets our [sic] specifications that will ensure that food will not be adulterated or misbranded when the processing, labeling, or repacking is completed. Jd. All four elements must be present and both parties must keep copies of the agreement and make it available for inspection by the FDA. The exemption cannot be claimed if the food will be adulterated after processing. [3] Efamol had no single, concise document satisfying the requirements of section 101.100. Instead, Efamol relies on a collection of several letters and facsimile transmissions. arguing that when read together, an agreement was formed which con- formed with the labeling exemption. We disagree. A simple reading of the documents demonstrates that each party had unresolved questions on the vitamin E content of the capsules, the use of preservatives, packaging requirements, the ap- pearance of EPO, Efamol’s order number, and “micro testing.” [4] The Food, Drug, and Cosmetic Act is a remedial measure. United States v. Dotterweich, 320 U.S. 277, 280-81 (1943). Misbranding was one of the chief evils Congress sought to stop when it enacted this legislation. 62 Cases of Jam v. United States, 340 U.S. 593, 596 (1951). Given Congress’ concern for proper labeling, we cannot find that the documents constitute an agreement. Rather than indicating an express intent to package the EPO capsules in a particular manner and ensure their purity, the documents reveal nothing more than a series of negotiations between Efamol and Banner for the encapsulation of EPO. —————EEEEE—eEeE————E A-7 Nowhere do the documents reflect a clear agreement that satis- fies the four requirements of 21 C.F.R. section 101.100(d)(2). Efamol has the burden of proving that the seized EPO was exempt from the labeling requirements under the Food, Drug{[,] and Cosmetic Act. United States v. Article of Device *** Toft- ness, 731 F.2d 1253, 1262 (7th Cir.), cert. denied, 469 U.S. 882 (1984). Because the communications submitted by Efamol fail to make a showing sufficient to establish the existence of an agreement under 21 C.F.R. section 101.100(d)(2), summary judgment was appropriate, Celotex, 477 U.S. at 322. ITT. Under the Food, Drug, and Cosmetic Act, a substance is a “food additive” when (1) it is intended for use as a component of a food; and (2) it is not generally recognized by qualified experts as safe under the conditions of its intended use. 21 U.S.C. § 321(s). “[A] food additive is presumed to be unsafe unless the Secretary of Health and Human Services has promul- gated a regulation ‘prescribing the conditions under which such additive may be safely used’ or providing for ‘investigational use by qualified experts.”” United States v. An Article of Food, 678 F.2d 735, 737 (7th Cir. 1982) (quoting 21 U.S.C. § 348(a) and (1)). [5] No such regulatory approval exists for EPO. Rather, Efamol contends that the sale of EPO is lawful because EPO is not a “food additive” at all, as defined by the FDA, and hence needs no regulatory approval. In particular, Efamol argues that EPO is generally recognized as safe, and hence does not fit the regulatory definition of “food additive.” “The burden of proving general recognition of safe use is placed on the proponent of the food substance in question.” United States v. An Article of Food, 752 F.2d 11, 15 (1st Cir. 1985) (citing 21 U.S.C. § 348(a) and (i)). ‘s A-8 To prove that EPO is generally recognized as safe, Efamol must (1) submit evidence establishing that scientifically trained experts qualified to evaluate EPO believe EPO is generally recognized as safe and (2) show that there is scientific data establishing the safety of EPO for use as a food supplement. Cf. Weinberger v. Bentex Pharmaceuticals, Inc., 412 U.S. 645. 652 (1973).3 Scientific studies which would support a finding that EPO is generally recognized as safe must be based on human. animal. analytical and other scientific studies. 21 C.F.R. § 170.3(h). This data must be colJected and analyzed with regard to EPO’s use as a dietary supplement. Furthermore, the information must be generally available to the community of experts and subjected to peer evaluation, criticism and review appropriate to establish such safety. 21 C.F.R. § 170.30(b); Bentex Pharmaceuticals. 412 US. at 652. The evidence submitted by Efamol or used by Efamol’s experts to evaluate EPO fails to meet the above criteria. Some of the data considered by Efamol’s experts concerns EPO’s use as a drug and not as a dietary supplement. Other data was based on unpublished materials, which were not subjected to peer evaluation. Thus, the opinions of Efamol’s experts were con- Subsequent to oral argument, Efamol submitted a “motion to vacate and remand for further proceedings” based on new precedent. Efamol’s motion is denied. First, the opinion cited by Efamol, United States v. Two Plastic Drums ... of an Article of Food ... Blackcurrant oil, No. 88-2398. slip op. (C.D. Ill. April 10, 1991) (hereinafter BCO), is from a district court and. therefore, is not binding precedent on this court. Second, the facts of BCO are distinguishable. In BCO the government seized two drums of bulk black currant oil. The district court foun< that other than a preservative, black currant oil was generally the sole ingredient of the capsule. Consequently, the court held that a single ingredient cannot be a food additive. In the present case, however, the evidence has shown that EPO is mixed with Vitamin E when encapsu- lated. Therefore, EPO is not a single ingredient and is properly considered a food additive. EEE A-9 taminated by their consideration of unsuitable evidence.‘ Cf. Daubert v. Merrell Dow Pharmaceuticals, Inc., 951 F.2d 1128, 1130 (9th Cir. 1991); Christophersen v. Allied-Signal Corp., 939 F.2d 1106, 1114 (Sth Cir. 1991) (en banc), petition for cert. filed, 60 U.S.L.W. 3406 (U.S. Dec. 3, 1991) (No. 91-785). In comparison, the government’s witnesses testified that there is insufficient published scientific literature showing that EPO is safe and there is insufficient animal or human testing of EPO’s use as a dietary supplement. [6] Thus, summary judgment was appropriate because Efamol failed to make a showing sufficient to establish the existence of an element essential to its case, and on which it bears the burden of proof at trial. Celotex, 477 U.S. at 322; United States v. Articles of Food and Drug ..., 518 F.2d 743, 747 (Sth Cir. 1975) (no genuine issue of material fact on the issue of general recognition of safety where evidence considered by plainuff’s experts was inappropriate). BV. We hold that the district court properly found that the labeling of bulk EPO as “PURE VEGETABLE OIL” is misbranding pursuant to 21 U.S.C. section 343. We also find that EPO is a “food additive” within 21 U.S.C. section 321 and that Efamol has failed to show that EPO is generally recognized as safe; therefore, summary judgment was appropriate. Efamol’s conduct comes four-square within the type of activity Congress sought to prohibit. AFFIRMED. During oral argument, Efamol conceded that in opposing the government's motion for summary judgment, (1) its experts relied on infor- mation never furnished to the government, despite the government’s dis- covery request; and (2) it had not previously relied on this information to establish that EPO was generally recognized as safe. We make no findings on the proprietary [sic] of Efamol’s actions. However, we do find, for the previously mentioned reasons, the additional data relied on by Efamol is insufficient under Rule 703 of the Federal Rules of Evidence. A-10 PRINTED FOR ADMINISTRATIVE OFFICE—U.S. COURTS BY BARCLAYS/ELECTROGRAPHIC SAN FRANCISCO—(415) 588-1155 The summary, which does not constitute a part of the opinion of the court, is copyrighted © 1992 by Barclays Law Publishers. en A-1] Not for Publication United States Court Of Appeals FOR THE NINTH CIRCUIT UNITED STATES OF AMERICA, Plaintiff-Appellee, V. 45/194 KG DRUMS OF PURE VEGETABLE OIL, et al, Defendant, & EFAMOL, LTD.., Claimant-Appellant. NO. 90-55086 D.C. No. CV-89-0073-MRP ORDER Before: KOZINSKI and O’SCANNLAIN, Circuit Judges, and McNAMEE,.” District Judge. The petition for rehearing is denied. The full court has been advised of the suggestion for en banc rehearing and no judge has requested a vote thereon. The suggesiiun for rehearing en banc is therefore rejected. Fed. R. App. P. 35(b). The Honorable Stephen M. McNamee, United States District Judge for the District of Arizona, sitting by designation. A-12 Not for Publication United States Court MOF Appeals FOR THE NINTH CIRCUIT \ UNITED STATES OF AMERIC ‘A, | Plaintiff-Appellee, \ 45/194 KG DRUMS OF PURF VEGETABLE OIL. et al. Defendant. & EFAMOL, LTD.. Claimant-Appellant NO. 90-55086 D.C. No. CV-89-0073-MRP ORDER Before: KOZINSKI and O'SCANNLAIN, Circuit Judges, and McNAMEE, District Judge. The motion to stay the mandate is GRANTED. The man- date will issue 30 days from the date of this order. The Honorable Stephen M. McNamee. United States District Judge for the District of Arizona, sitting by designation. United States Histrict Court CENTRAL DISTRICT OF CALIFORNIA UNITED STATES OF AMERICA, Plaintiff. 15/194 kg. drums ... “PURE VEGETABLE OIL ...’ Defendant CASE NO. CV 89-73 MRP FINDINGS OF FACT AND CONCLUSIONS OF LAW Plaintiff's Motion for Summary Judgment and Claimant’s Cross Motion for Summary Judgment came on for hearing before the Honorable Mariana R. Pfaelzer on October 23, 1989. The Court, having considered the memoranda, affidavits, and exhibits filed by the parties and heard oral argument, makes the following Findings of Fact and Conclusions of Law FINDINGS OF FACT 1. This action was filed by the United States of America pursuant to the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 301 et seg., to have seized and condemned, pursuant to 21 U.S.C. § 334, 45/194 kg. drums, one/130 kg. drum, and one/45 kg. drum of an article of food labeled in part “PURE VEGETABLE OIL”. The 47 drums contained oil pressed from the evening primrose plant (hereafter called evening primrose oil). 2. The complaint for forfeiture was filed on January 6, 1989. ee A-14 3. The evening primrose oil was seized by the United States Marshal on January 31, 1989 at Banner Gelatin Products in Chatsworth, California (“Banner”) 4. Thereafter, on February 13, 1989. Efamol Ltd. (“Efamol’) intervened in this action and filed a claim and an ANnSWeT \. The evening primrose oil had been shipped in interstate commerce prior to the seizure. 6. Atthe time the evening primrose oil was seized. it was being held for the purpose of further processing and sale. — The seized evening primrose oil was intended for use ds a component of a nutritional or dietary supplement. 8. When introduced into and while in interstate com merce, and while held for sale after shipment in interstate commerce, the seized drums of evening primrose oil were labeled “PURE VEGETABLE OIL”. Y. When introduced into and while in interstate com- merce, and while held for sale after shipment in interstate commerce, the seized drums of evening primrose oil were not labeled “evening primrose oil” or “oil of evening primrose”. 10. When evening primrose oil is promoted, marketed, and discussed in the public and scientific literature in the United States, it is called “evening primrose oil”. 11. Evening primrose oil is commonly and usually referred to as “evening primrose oil”. 12. With regard to the seized evening primrose oil, there 1S NO written agreement between Efamol and Banner that was signed by both parties, contains the post office addresses of both parties, and sets out specifications that ensure that the evening primrose oil would not be adulterated or misbranded when its processing is completed. en A-15 13. Labeling oil as “PURE VEGETABLE OIL” without further qualification in effect represents to consumers that the product ts intended for use as a cooking or salad oil rather than as a nutritional or dietary supplement. 14. Drs. Robert E. Olson, Garret A. FitzGerald, William A. Sibley, Howard W. Sprecher, John E. Vanderveen, Hilteye lrausquin, and Gloria J. Troendle-—experts qualified by scien tific training and experience to evaluate the safety of evening primrose oil—do not consider evening primrose oil to be generally recognized as safe for use as a nutritional or dietary supplement. 16. Drs. Olson, FitzGerald, Sibley, Sprecher, Vander veen, lrausquin, and Troendle do not recognize evening prim rose oil as having been shown through scientific procedures to be safe for use as a nutritional or dietary supplement. CONCLUSIONS OF LAW 1. Evening primrose oil is a food within the meaning of 21 U.S.C. § 321(f). 2. The seized evening primrose oil was being held for sale after shipment in interstate commerce within the meaning of 21 U.S.C. § 334(a)(1). 3. The seized evening primrose oil is misbranded within the meaning of 21 U.S.C. § 343(1)(1) because its labeling fails to bear the common or usual name of the article. 4. The seized evening primrose oi! is misbranded within the meaning of 21 U.S.C. § 343(a)(1) because the labeling on the drums states that the productis “PURE VEGETABLE OIL” which is misleading. 5. Evening primrose oil is not generally recognized as safe by qualified experts, and is therefore a food additive within the meaning of 21 U.S.C. § 321{s). A-16 6. There is no regulation in effect permitting the use of evening primrose oil as a food additive or exempting evening primrose oil from the food additives requirements of the Federal Food, Diug, and Cosmetic Act: 7. Evening primrose oil is an unsafe ys additive and adulterated within the meaning of 21 U.S.C. §§ 342(a)(2)(C) and 348. 5. The evening primrose oil is subject to condemnation and destruction pursuant to 21 U.S.C. §§ 331 (a). 331(b), and 334(a)(1). 9. Claimant has failed to show the existence of a genuine issue of material fact, and plaintiff is therefore entitled to judg- ment as a matter of law. DATED: /s/ Mariana R. Pfaelzer Mariana R. Pfaelzer United States District Judge A-17 United States Histrict Court CENTRAL DISTRICT OF CALIFORNIA UNITED STATES OF AMERICA, Plaintiff, Vv. 45/194 kg. drums ...“PURE VEGETABLE OIL ...” Defendant. CASE NO. CV 89-73 MRP ORDER AND JUDGMENT Plaintiff's Motion for Summary Judgment and Claimant’s Cross Motion for Summary Judgment came on for hearing before the Honorable Mariana R. Pfaelzer on October 23, 1989. The Court, having heard oral argument and considered the memoranda, affidavits, and exhibits filed by the parties, and in accordance with the Findings of Fact and Conclusions of Law filed herewith, IT IS ORDERED, ADJUDGED AND DECREED that, 1. Summary judgment be, and the same hereby is, entered in favor of the United States of America, and against the defen- dants, condemning and forfeiting the defendants herein to the United States of America; and 2. Claimant’s Motion for Summary Judgment be denied. DATED: November 27, 1989 /s/ Mariana R. Pfaelzer Mariana R. Pfaelzer United States District Judge A-18 21 U.S.C. § 321(s) § 321. Definitions; generally For the purpose of this chapter — (s) The term “food additive” means any substance the intended use of which results or may reasonably be expected tc result, directly or indirectly, in its becoming a component or otherwise affecting the characteristics of any food (including any substance intended for use in producing, manufacturing, packing, processing, preparing, treating, packaging, transport- ing, or holding food; and including any source of radiation intended for any such use), if such substance is not generally recognized, among experts qualified by scientific training and experience to evaluate its safety, as having been adequately shown through scientific procedures (or, in the case of a sub- stance used in food prior to January 1, 1958, through either scientific procedures or experience based on common use in food) to be safe under the conditions of its intended use; except that such term does not include— (1) a pesticide chemical in or on a raw agricul- tural commodity; or (2) a pesticide chemical to the extent that it is intended for use or is used in the production, storage, or transportation of any raw agricultural commodity; or (3) acolor additive: or (4) any substance used in accordance with a sanction or approval granted prior to September 6, 1958 pursuant to this chapter, the Poultry Products Inspection Act (21 U.S.C. 451 and the following) or the Meat Inspection Act of March 4, 1907. as amended and extended; or (5) anew animal drug. Se A-19 21 U.S.C. § 342(a)(1) and (2) § 342. Adulterated food A food shall be deemed to be adulterated— Poisonous, insanitary, etc., ingredients (a) (1) If it bears or contains any poisonous or deleterious substance which may render it injurious to health: but in case the substance is not an added substance such food shall not be considered adulterated under this clause if the quantity of such substance in such food does not ordinarily render it injurious to health; or (2) (A) if it bears or contains any added poisonous or added deleterious substance (other than one which is (i) a pesticide chemical in or on a raw agricultural commodity; (ii) a food additive; (iii) a color additive; or (iv) a new animal drug) which is unsafe within the meaning of section 346 of this title, or (B) if it is a raw agricultural commodity and it bears or contains a pesticide chemical which is unsafe within the mean- ing of section 346a(a) of this title, or (C) if it is, or it bears or contains, any food additive which is unsafe within the meaning of section 348 of this title: Provided, That where a pesticide chemical has been used in or on a raw agricultural commodity in conformity with an exemption granted or a tolerance prescribed under section 346a of this title and such raw agricul- tural commodity has been subjected to processing such as canning, cooking, freezing, dehydrating, or milling, the residue of such pesticide chemical remaining in or on such processed food shall, notwithstanding the provisions of sections 346 and 348 of this title, not be deemed unsafe if such residue in or on the raw agricultural commodity has been removed to the extent possible in good manufacturing practice and the concentration of such residue in the processed food when ready to eat is not greater than the tolerance prescribed for the raw agricultural commodity. .. . A-20 21 U.S.C. § 343(a)(1) and (i)(1) § 343. Misbranded food A food shall be deemed to be misbranded (a) If (1) its labeling is false or misleading in any particular (1) Unless its label bears (1) the common ol! usual name of the food, if any there be... . A-2] 21 U.S.C. § 348 § 348. Food additives—Unsafe food additives; exception for conformity with exemption or regulation (a) A food additive shall, with respect to any particular use or intended use of such additives, be deemed to be unsafe for the purposes of the application of clause (2) (C) of section 342(a) of this title, unless— (1) it and its use or intended use conform to the terms of an exemption which is in effect pursuant to subsection (i) of this section; or (2) there is in effect, and it and its use or intended use are in conformity with, a regulation issued under this section prescribing the conditions under which such additive may be safely used. While such a regulation relating to a food additive is in effect, a food shall not, by reason of bearing or containing such an additive in accordance with the regulation, be considered adul- terated within the meaning of clause (1) of section 342(a) of this title. A-22 21 C.F.R. § 101.100(d)(2) § 101.100 Food; exemptions from labeling. (d) Except as provided by paragraphs (e) and (f) of thi: section, a shipment or other delivery of a food which is. it accordance with the practice of the trade. to be processed labeled, or repacked in substantial quantity at an establishmen other than that where originally processed or packed, shall be exempt, during the time of introduction into and movement ir interstate commerce and the time of holding in such estab- lishment, from compliance with the labeling requirements ot section 403(c), (e), (g), (h), (i), (j), and (k) of the act if: (2) Incase such person is not such operator, such shipment or delivery is made to such establishment under a written agreement, signed by and containing the post office addresses of such person and such operator, and containing such specifica- tions for the processing, labeling, or repacking, as the case may be, of such food in such establishment as will ensure. if such specifications are followed, that such food will not be adul- terated or misbranded within the meaning of the act upon completion of such processing, labeling, or repacking. Such person and such operator shall each keep a copy of such agree- ment until 2 years after the final shipment or delivery of such food from such establishment, and shall make such copies availabie for inspection at any reasonable hour to any officer or employee of the Department who requests them. ss, eimai lai A-23 21 C.F.R. § 170.30 § 170.30 Eligibility for classification as generally recognized as safe (GRAS). (a) General recognition of safety may be based only on the views of experts qualified by scientific training and experience to evaluate the safety of substances directly or indirectly added to food. The basis of such views may be either (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through experience based on common use in food. General recognition of safety requires common knowledge about the substance throughout the scientific com- munity knowledgeable about the safety of substances directly or indirectly added to food. (b) Genera! recognition of safety based upon scientific procedures shall require the same quantity and quality of scien- tific evidence as is required to obtain approval of a food additive regulation for the ingredient. General recognition of safety through scientific procedures shall ordinarily be based upon published studies which may be corroborated by unpublished Studies and other data and information. A-24 FEDERAL REGISTER Vol. 55, No. 57, at 10932 Friday, March 23, 1990 RULES AND REGULATIONS DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 184 [Docket Nos. 87G-0418 and 87F-0416] Direct Food Substances Affirmed as Generally Recognized as Safe; Chymosin Enzyme Preparation Derived From Escherichia Coli K-12 AGENCY: Food and Drug Administration. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending its regulations to affirm that the use of chymosin preparation derived by fermentation from Escherichia coli K-12 is generally recognized as safe (GRAS). This action is in response to a petition filed by Pfizer Central Research. Pfizer, Inc. EFFECTIVE DATE: March 23, 1990. The Director of the Office of the Federal Register approves the incorporation by reference in accordance with 5 U.S.C. 552(a) of a certain pub- lication in 21 CFR 184.1685(b) effective on March 23, 1990. FOR FURTHER INFORMATION CONTACT: Eric L. Flamm, Center for Food Safety and Applied Nutrition (HFF- 334), Food and Drug Administration, 200 C Street SW.. Washington, DC 20204, 202-426-8950. ne A-25 SUPPLEMENTARY INFORMATION: I. Background In accordance with the procedures described in § 170.35 (21 CFR 170.35), Pfizer Central Research (Pfizer) submitted a petition (GRASP 8G0337) requesting that its chymosin prepara- tion (referred to as “chymosin” in the petition’s filing notice that FDA published in the Federal Register of February 9, 1988 (53 FR 3792)), which is derived from the fermentation of a geneti- cally modified FE. coli K-12, be affirmed as GRAS as a direct human food ingredient. Chymosin is the principal enzyme in rennet, a GRAS food ingredient used for its milk-clotting ac- tivity, and is primarily responsible for that activity. Chymosin preparation is intended for use as a substitute for rennet. To avoid confusion between chymosin the enzyme and chymosin the enzyme preparation (in which chymosin is the principal active component but which may also contain im- purities), this document will henceforth use the term “chymosin” when referring to the enzyme and “chymosin preparation” when referring to the fermentation-derived chymosin enzyme preparation. Pfizer submitted two petitions concerning chymosin preparation. In addition to GRASP 8G0337, it submitted a petition (FAP 8A4048) requesting that the food additive regula- tions be amended to provide for the safe use of genetically modified E. coli K-12 as a source of chymosin preparation (referred to as “chymosin” in the petition’s filing notice that FDA published in the Federal Register of February 9, 1988 (53 FR 3792)), for use in food. The regulation that is the subject of this final rule is in response to the GRAS affirmation petition. Published elsewhere in this issue of the Federal Register is a document (Docket No. 87F-0416) announcing that Pfizer has withdrawn its food additive petition without prejudice to a future filing. A-26 FDA gave interested parties an opportunity to submit cor ments concerning the GRAS affirmation petition to the Docke Management Branch (HFA-305), Food and Drug Administr tion, Rm. 4-62, 5600 Fishers Lane, Rockville, MD 20857. FD received two comments in response to the notice. Both cor ments address whether the dairy industry needs new sources | chymosin. Neither comment contains any information releva: to the safety, functionality, environmental impact, or GRA Status of the food use of the subject chymosin preparation. Thu the comments are not relevant to the agency's evaluation « chymosin preparation. FDA’s authority in reviewing food add tive and GRAS affirmation petitions is limited to questior about the safety and functionality of the substance at issue an does not include questions about the need for a new foo ingredient (21 U.S.C. 348). II. Standards for GRAS Affirmation Pursuant to § 170.30 (21 CFR 170.30), general recognitio of safety may be based only on the views of experts qualifie by scientific training and experience to evaluate the Safety substances. The basis of such views may be either (1) scientifi procedures or (2) in the case of a substance used in food prio to January 1, 1958, experience based on common use in fooc General recognition of safety based upon scientific procedure requires the same quantity and quality of scientific evidence a is required to obtain approval of a food additive regulation an ordinarily is to be based upon published studies, which may b corroborated by unpublished studies and other data and infor mation (§ 170.30(b)). In its petition, Pfizer has relied upo! scientific procedures to establish that chymosin preparation i GRAS. Rennet is an animal-derived enzyme preparation that i GRAS as specified in § 184.1685 (21 CFR 184.1685). There fore, if published information shows that the principal active component of chymosin preparation is the same as that of rennet A-27 and that the other components (i.e., impurities) of the chymosin preparation, which may differ from the other components (i.e., impurities) of rennet, do not render the use of the substance unsafe, then chymosin preparation derived from E. coli would present no more safety concern than rennet. If this is the case, FDA can affirm chymosin preparation derived from E. coli as GRAS for use as a replacement for rennet. II. Safety A. Introduction Chymosin, also known as rennin, is the principal milk-clot- ting enzyme present in rennet (Ref. 1). Rennet is an enzyme preparation that will clot milk, forming it into curds and whey (Refs. 1 and 2). It is used to make cheese and other dairy products. It has a long and extensive history of safe use in food and has been affirmed by FDA as GRAS in § 184.1685 (48 FR 51151; November 7, 1983). Food-grade rennet is an enzyme preparation that is derived from the fourth stomach of calves, kids, or lambs. Commercial- ly, it is generally derived from unweaned calves by aqueous extraction. The aqueous extraction step is followed by purifica- tion steps and an acidification step to cleave prochymosin (the inactive precursor of chymosin) in the rennet into chymosin (Ref. 1). There are two predominant forms of calf chymosin, chymosin A and chymosin B (Ref. 1). Foltmann et al. have shown thatchymosin A and chymosin B differ by a single amino acid (Ref. 3). In this document FDA is using the terms “chymosin” to refer to either, or both, chymosin A and chymosin B. mt Techniques developed in the last 15 years (frequently termed “recombinant DNA technology” or “cloning techni- ques’’) enable scientists to locate and to obtain a segment of deoxyribonucleic acid (DNA) containing a gene of interest. A-28 They are able to move that DNA segment into a vector (a self-replicating DNA molecule that is easy to manipulate) and then introduce it into a new host organism where it can be correctly expressed (that is, produce the protein that it would produce in the original organism). These techniques are well- known to molecular biologists. (see e.g., Refs. 4 and 5). B. The Chymosin Component Using cloning techniques, scientists in a number of dif- ferent laboratories have identified the gene in the calf from which the chymosin in rennet is produced, the prochymosin gene (Refs. 6 through 8). Scientists have moved the calf prochymosin gene into E. coli (Refs. 6 through 10) as well as into other microorganisms (Refs. 11 through 13). They have used a variety of techniques to demonstrate that they have cloned full-length copies of the correct gene. Such techniques include: (1) DNA sequencing, whereby the cloned putative prochymosin gene was shown to have the nucleotide sequence that encodes the amino acid sequence of prochymosin (Refs. 6 through 8); (2) nucleic acid hybridization, whereby the cloned DNA fragments or the ribonucleic acid (RNA) molecules made from the DNA fragments were shown to hybridize (i.e., specifically bind) with complementary DNA in the prochymosin gene (Refs. 7 through 12); and (3) physical map- ping, whereby the cloned DNA fragments were shown to be large enough to contain the prochymosin gene and, when digested with appropriate DNA-cutting enzymes and run on gels that separate DNA fragments by size, were shown to yield the pattern of DNA fragments expected for prochymosin (Refs. 7 through 13). The published evidence establishes that the new host or- ganisms are able to use the prochymosin gene to produce prochymosin that has the same molecular weight as prochymosin found in calf rennet (Refs. 9 through 11 and 13 through 15). It also establishes that the prochymosin that is ee A-29 produced (cloned prochymosin) can be cleaved into chymosin (cloned chymosin) that has the same molecular weight and the same functional activity as chymosin found in calf rennet (Refs. 9, 10, and 12 through 15). The molecular weights of prochymosin and chymosin were assayed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a technique that enables one to determine the comparative molecular weight of proteins based on their rate of migration through the gel. Cloned prochymosin was found to migrate through these gels at the same rate as the prochymosin derived from calves (Refs. 9 through 11 and 13 through 15). Cloned chymosin was found to migrate through these gels at the same rate as the chymosin found in rennet (Refs. 9, 10, and 12 through 15). The functional activity of chymosin that was measured was milk-clotting activity. Cloned chymosin was found to clot milk at the same rate as the chymosin in rennet under various tempera- tures, salt concentrations, and pH conditions (Refs. 9 through 15). One safety concern raised by cloning is whether extraneous DNA, particularly DNA flanking the gene of interest, that could potentially encode extraneous harmful proteins may be cloned along with the gene of interest (i.e., prochymosin). However, the regulation stipulates that the substance being affirmed as GRAS is one that is produced using a production strain that is nontoxigenic (see § 184.1685(a)(2)). If the cloned DNA encodes a harmful substance that could render the enzyme preparation unsafe, the production strain would be toxigenic, and the sub- stance produced would not be GRAS under § 184.1685(a)(2). Therefore, the agency finds that there is no basis for concern that the safety of the chymosin preparation will be compromised by contaminating proteins encoded by extraneous uncharacterized DNA cloned along with the prochymosin gene. A-30 FDA notes that as a matter of good manufacturing practice, manufacturers using recombinant DNA technology should as sure themselves that they have not inadvertently cloned ex- traneous protein-encoding DNA along with the prochymosin gene. Such assurance can come from reviewing the details of the cloning steps, such as the origin and sequence of the DNA fragments used in the cloning, and from full characterization of the final genetic constructs via techniques such as DNA se quencing. The agency points out that Pfizer’s petition contains information demonstrating that it conducted these steps. Based on the fact that published information demonstrates that chymosin produced from the cloned prochymosin gene has the same molecular weight and the same functional activity as the chymosin derived from calves, FDA concludes that the chymosin enzyme in chymosin preparation is the same as the chymosin enzyme in calf rennet. Therefore, FDA concludes that the chymosin enzyme in chymosin preparation is as safe as the chymosin enzyme in rennet. C. Sources of Impurities Enzyme preparations used in food-processing are usually not chemically pure but contain extraneous source (cellular) and processing material. The nature and amounts of these impurities in the finished enzyme preparation depend on the organism from which the enzyme is produced (the source or production or- ganism), the fermentation materials and methods used to grow the production organism, and the materials and methods used to generate the finished enzyme preparation. Both the source material and the manufacturing methods for producing chymosin preparation differ from those used to produce animal rennet. Therefore, the impurities in chymosin preparation will differ from those in rennet. The question thus is whether the source material or manufacturing methods for chymosin preparation will introduce impurities that would raise concems about the safety of the preparation. |. Processing steps Researchers in a number of laboratories have published papers containing descriptions of methods that they used for producing chymosin preparation from microorganisms contain ing the calf prochymosin gene (e.g., Refs. 9 through 15). The methods described in these publications and in Pfizer’s petition do not differ from each other in any significant way. The key steps in the methods, as described by Marston et al. (Ref. 15) and by Pfizer, are summarized below. E. coli is grown in a liquid nutrient medium, then pelleted by centrifugation. The pelleted cells are resuspended in a small volume of buffer and burst open, releasing the prochymosin in the form of densely packed insoluble aggregates. The aggregates are recovered by a second centrifugation step, while most of the rest of the cellular protein and debris remain in suspension. The prochymosin is thus rapidly purified from the bulk of cellular material. Pfizer treats the aggregates with acid to kill residual cells and to degrade residual DNA. The prochymosin aggregates are solubilized by denaturation in an alkaline urea solution. The prochymosin is renatured by decreasing the alkalinity and dilut- ing out the urea and further purified by ion-exchange chromatography. The prochymosin is converted to chymosin, the active form of the enzyme, by suspension in a pH 2 acid solution for an hour. The final chymosin preparation is a clear solution. ; FDA finds that the manufacturing method does not require the use of any processing materials that are not GRAS or approved food additives. Accordingly, it is specifying in the regulation that the substance being affirmed as GRAS is one that is-produced using only processing materials that are GRAS substances or food additives approved for use in this type of process (see § 184.1685(a)(2)). Therefore, the agency concludes that the manufacturing steps will not introduce impurities into A-32 the enzyme preparation that will adversely affect the safety of the preparation. 2. Production organism The source material for the chymosin in chymosin prepara- tion is FE. coli K-12. E. coli’s natural habitat is the large intestine of humans and animals, where it is found at 1 million to 100 million organisms per gram of intestinal contents (Ref. 16). E. coli K-12 is a laboratory strain that, through longtime propaga- tion in the laboratory, has lost a number of the traits necessary for colonization of, and therefore survival in, the intestinal tract (Ref. 17). E. coli K-12 is one of biology’s most extensively studied microorganisms. It has been shown to be nonpathogenic and nontoxigenic in studies in which it has been fed to humans and laboratory animals (see, e.g., Refs. 16 and 17) and in detailed studies of its phenotypic and genotypic traits (see, e.g., Refs. 16 through 18). For example, Gorbach (Ref. 16), Curtiss (Ref. 17), and Smith (Ref. 18) have reported their own and others’ failed attempts to implant E. coli K-12 in the human intestine, an initia! step for pathogenicity. In none of the experiments were re- searchers able to isolate the strain from the feces of volunteers 1 to 6 days after they were fed high doses (10°-10'° live organisms) of various strains of E. coli K-12. In none of the experiments did the volunteers become sick as a result of their ingestion of the organisms. Gorbach (Ref. 16) discussed six factors necessary for an organisms to be pathogenic: (1) Survival in the environment, (2) a mechanism for penetrating the skin or mucosal surface, (3) multiplication within the host, (4) systemic spread within the host, (5) resistance to host defense mechanisms, and (6) produc- tion of a toxin or some other mechanism to damage the host to produce disease symptoms. He noted that a lack of any one of these characteristics will render the microorganisms non- pathogenic, and that, based on the available evidence, E. coli iJ A-33 K-12 is deficient in every one of these factors (Ref. 16). Gorbach also noted that in the 30 years that E. coli K-12 has been used in genetics research, there have been no reported cases of laboratory-acquired infections from this organism (Ref. 16). As corroborative evidence of the safety of chymosin preparation, Pfizer submitted two unpublished short-term in vivo studies conducted on its enzyme preparation, a 5-day feeding study in dogs and a 1-month gavage study in rats (Ref. 19). No adverse effects were observed in these studies at any dose fed. Some E. coli K-12 strains, such as those that are used by Pfizer and others (e.g., Refs. 9, 10, and 14) to produce chymosin preparation, do contain marker genes that encode resistance to clinically useful antibiotics. Such genes potentially could be transferred to other microorganisms with which the production strain or its DNA comes into contact. However, as previously described, the isolation of the enzyme as an intracellular in- soluble aggregate results in the destruction of the microorganism and in the elimination of most cellular material, including these marker genes (Ref. 15). Additionally, the two acid treatment steps in the manufacturing process inactivate residual cells and degrade residu [Text truncated at 120,000 characters. The full text is on the page linked above.] --- Source: Frix Law Library, https://www.frixlaw.com/law-library/documents/brief%3Amicro_IA40386011_1042%3A1. Public record. Not legal advice.