Berlex Laboratories, Inc. v. Food and Drug Admin.

Citation942 F.Supp. 19
Decision Date07 October 1996
Docket NumberCivil Action No. 96-0971 (JR).
PartiesBERLEX LABORATORIES, INC., Plaintiff, v. FOOD AND DRUG ADMINISTRATION, et al., Defendants.
CourtU.S. District Court — District of Columbia

James R. Phelps, Robert A. Dormer, A. Wes Siegner, Jr., Hyman, Phelps & McNamara, P.C., Washington, DC, for Plaintiff.

Drake Cutini, Office of Consumer Litigation, U.S. Department of Justice, Washington, DC, for Defendants.

Allen R. Snyder, Robert P. Brady, Douglas A. Fellman, Gregory G. Garre, Hogan & Hartson, Washington, DC, William C. Brashares, William A. Davis, Michael B. Bressman, Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C., Washington, DC, Michael J. Astrue, Elan Z. Ezickson, Biogen, Inc., Cambridge, MA, for Intervenors.

MEMORANDUM OPINION

ROBERTSON, District Judge.

Plaintiff Berlex Laboratories, Inc. ("Berlex") manufactures Betaseron, a biological drug classified as an interferon beta product.1 On July 23, 1993, the Food and Drug Administration approved Betaseron for the treatment of multiple sclerosis. Because it was the first interferon beta product approved for the treatment of MS, Betaseron was also given market exclusivity for seven years under the Orphan Drug Act. 21 U.S.C. §§ 360aa-360dd.

Intervenor-defendant Biogen, Inc. developed an interferon beta product similar to Betaseron. On May 17, 1996, the FDA approved Biogen's product, known as Avonex, for manufacture and sale in the United States for the treatment of MS.

In this action, Berlex seeks a judgment declaring that FDA's approval of Biogen's Avonex was unlawful and an order rescinding that approval. Berlex's claims are that FDA 1) unlawfully nullified Betaseron's Orphan Drug protection upon an arbitrary and capricious finding that Avonex is "clinically superior" to Betaseron; 2) violated the Public Health Service Act, 42 U.S.C. § 262, and regulations issued thereunder by approving Avonex without requiring the completion of full clinical trials; and 3) failed to conduct required notice-and-comment rulemaking before issuing a "comparability guidance document" that was important to the approval of Avonex.

Biogen has intervened as a defendant. Cross-motions for summary judgment were argued on September 5, 1996. This memorandum sets forth the reasons for the accompanying order granting the motions of FDA and Biogen and denying the motion of Berlex.

BACKGROUND

FDA's approval of Avonex on May 17, 1996, marked the first time FDA had approved a biological product for manufacture and sale without requiring the completion of full clinical trials on that actual product. In approving Avonex, FDA allowed Biogen to rely on the results of a clinical study of another company's interferon beta product, known as BG9015, after concluding that BG9015 was "comparable" to Avonex.

BG9015 was manufactured in Laupheim, Germany, by a joint venture owned half by Biogen and half by Rentschler Technology. This joint venture commissioned Dr. Lawrence Jacobs to do a clinical study of BG9015 in the United States beginning in 1990. In 1993, while the clinical trial was going on, the joint venture failed and went into receivership. Production of BG9015 ceased, but researchers had enough BG9015 to complete the clinical trials, which ended in 1994. AR 2, 157-58.

As early as 1991, Biogen had begun separately producing interferon beta products similar to BG9015 at a manufacturing site in Cambridge, Massachusetts. After the Biogen-Rentschler joint venture failed, Biogen sought FDA approval of a new interferon beta, known as BG9216. Rather than conduct new clinical trials of BG9216, Biogen sought to rely on the Jacobs study and sought to demonstrate to FDA that BG9216 and BG9015 were comparable. The FDA concluded that BG9216 and BG9015 were not comparable, however, and declined to consider data from the Jacobs study in connection with the application of BG9216. AR 2.

Biogen then developed the interferon beta cell line that ultimately became Avonex and submitted it for FDA approval. Although FDA had invariably required full-scale clinical trials for new biological drugs in the past, Biogen again sought to rely on the results of the Jacobs study conducted on BG9015, asserting that Avonex was comparable to BG9015. This time FDA agreed. After extensive biological, biochemical, and biophysical analyses, as well as pharmacokinetic studies in humans, FDA concluded that BG9015 and Avonex were "comparable" — that they were "biochemically and functionally equivalent" — and permitted the Jacobs study to be used in place of a separate clinical trial of Avonex itself. AR 2-10, 55-57.

Before Avonex could be approved for sale in the face of Betaseron's exclusivity under the Orphan Drug Act, FDA also had to make a finding that Avonex was "different" from Betaseron. FDA made that finding, basing its conclusion on the substantially less frequent occurrence of the death of skin tissue in the injection area, or injection site necrosis, associated with Avonex.2 AR 29. FDA also noted that four percent of Avonex patients experience injection site reactions, such as swelling, redness or tenderness, compared to 85 percent of Betaseron patients. On the basis of those comparisons, FDA found Avonex "clinically superior" to Betaseron and therefore "different" for Orphan Drug Act purposes.

On May 17, 1996, FDA approved Avonex "for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations." AR 1.

Approximately three weeks before FDA approved Avonex, it issued and published in the Federal Register a "guidance document." This document stated that FDA regulations permit the approval of biological products on the basis of "clinical data generated from a precursor product, made prior to a manufacturing change" so long as the manufacturer "can demonstrate that the precursor product is comparable to the manufactured product." FDA Guidance Concerning Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products ("Comparability Guidance Document"), 3. FDA did not cite or refer to the "comparability guidance document" as a basis for its approval of Avonex. The principles and language embodied in the guidance document, however, were present in the document that announced FDA's approval of Avonex.

ANALYSIS

As a preliminary matter, it should be noted that this decision proceeds from an examination not only of the pleadings, but also of the administrative record. Defendants' motions have been treated as motions for summary judgment. Marshall County Health Care Auth. v. Shalala, 988 F.2d 1221, 1226 n. 5 (D.C.Cir.1993). Affidavits submitted by Berlex have not been considered, nor are they deemed to be part of the record of this case. See Camp v. Pitts, 411 U.S. 138, 142-43, 93 S.Ct. 1241, 1244, 36 L.Ed.2d 106 (1973).

1. Elimination of Berlex's market exclusivity

Congress passed the Orphan Drug Act in 1983 to encourage the development of drugs for the treatment of rare diseases.3 21 U.S.C. §§ 360aa-360dd. The Act provides seven-year market exclusivity for orphan drugs and precludes the grant of FDA approval to other manufacturers of the same drug intended for treatment of the same disease. 21 U.S.C. § 360cc. The statute does permit FDA approval of a drug that treats the same condition as did the original orphan drug if FDA determines that the two drugs are not the same. FDA's implementing regulations provide that a new drug will not be considered the same as a previously approved drug if the new drug is "clinically superior." 21 C.F.R. § 316.3(b)(13)(ii). The regulations provide further that a new drug is "clinically superior" if it offers "[g]reater safety in a substantial portion of the target populations...." 21 C.F.R. § 316.3(b)(3)(ii). Applying those regulations to Avonex and relying primarily upon the disparity in the incidence of injection site necrosis caused by Betaseron (5%) and Avonex (0%), FDA concluded that Avonex was safer than Betaseron and therefore a "different" drug. AR 29, 502-03.

Berlex challenges FDA's decision that Avonex is "clinically superior" to Betaseron. Berlex argues that it was arbitrary and capricious for FDA to rely exclusively on a single side effect when making that determination and contends that FDA should instead have compared the "overall safety profiles" of Avonex and Betaseron.

The Orphan Drug Act is silent as to the nature of the analysis FDA must undertake when deciding whether one drug is clinically superior to another. The regulations provide as an example of "greater safety" the elimination of "an ingredient or contaminant that is associated with relatively frequent adverse effects." 21 C.F.R. § 316.3(b)(3)(ii). FDA has interpreted its regulations to mean that even "a small demonstrated ... diminution in adverse reactions may be sufficient to allow a finding of clinical superiority." 57 Fed.Reg. 62076, 62078 (Dec. 29, 1992). That interpretation is entitled to the court's deference. Lyng v. Payne, 476 U.S. 926, 939, 106 S.Ct. 2333, 2341-42, 90 L.Ed.2d 921 (1986).

FDA's application of that interpretation in a specific case must be upheld if the agency based its decision upon relevant factors that have evidentiary support. Ritter Transportation, Inc. v. ICC, 684 F.2d 86, 88 (D.C.Cir.1982), cert. denied, 460 U.S. 1022, 103 S.Ct. 1272, 75 L.Ed.2d 494 (1983). The substantial disparity between Avonex and Betaseron with regard to injection site necrosis was surely a factor relevant to safety, and Berlex does not challenge the sufficiency of the record evidence on that point. FDA had an adequate basis upon which to consider Avonex "clinically superior" to Betaseron, and its decision that Avonex is "different" for purposes of the Orphan Drug Act will not be disturbed.

2. Approval of Avonex without separate clinical trials

Berlex next asserts that FDA's approval of Avonex...

To continue reading

Request your trial
6 cases
  • Am. Acad. Pediatrics v. Food & Drug Admin.
    • United States
    • U.S. District Court — District of Maryland
    • 15 Mayo 2019
    ...States Food & Drug Admin. , No. DKC-14-3607, 2015 WL 13091366, at *11 (D. Md. July 29, 2015) (quoting Berlex Labs., Inc. v. Food & Drug Admin. , 942 F.Supp. 19, 26 (D.D.C. 1996) (quoting 5 U.S.C. § 553 )); see also Perez v. Mortg. Bankers Ass'n , ––– U.S. ––––, 135 S.Ct. 1199, 1206, 191 L.E......
  • Allergan, Inc. v. Crawford
    • United States
    • U.S. District Court — District of Columbia
    • 19 Enero 2005
    ...States v. Rutherford, 442 U.S. 544, 553-54, 99 S.Ct. 2470, 61 L.Ed.2d 68 (1979); Serono Labs., 158 F.3d at 1320; Berlex Labs., Inc. v. FDA, 942 F.Supp. 19, 25 (D.D.C.1996). While its choice is not the only logical course it could have adopted, FDA's considered response to Allergan's citizen......
  • Rempfer v. Von Eschenbach
    • United States
    • U.S. District Court — District of Columbia
    • 29 Febrero 2008
    ...because of the breadth of Congress' delegation of authority to FDA and because of FDA's scientific expertise." Berlex Labs., Inc. v. FDA 942 F.Supp. 19, 25 (D.D.C.1996). In reviewing an administration action such as the FDA's Final Order at issue here, the role of the district court is to "......
  • Mallinckrodt Inc. v. U.S. Food & Drug Admin.
    • United States
    • U.S. District Court — District of Maryland
    • 29 Julio 2015
    ...2014 Draft Guidance was an interpretive rather than a legislative rule, as it is dispositive. In Berlex Laboratories, Inc. v. Food and Drug Administration, 942 F.Supp. 19, 25-27 (D.D.C. 1996), the United States District Court for the District of Columbia addressed whether a guidance documen......
  • Request a trial to view additional results

VLEX uses login cookies to provide you with a better browsing experience. If you click on 'Accept' or continue browsing this site we consider that you accept our cookie policy. ACCEPT