Association of American, Phys. & SG. Inc. v. U.S. Food & Drug Ad., Civil Action 00-02898 (HHK) (D. D.C. 10/17/2002), Civil Action 00-02898 (HHK).

CourtUnited States District Courts. United States District Court (Columbia)
Writing for the CourtHenry H. Kennedy
Decision Date17 October 2002
Docket NumberCivil Action 00-02898 (HHK).

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Civil Action 00-02898 (HHK).
United States District Court, District of Columbia.
October 17, 2002.

Daniel E. Troy, Food & Drug Administration, Office of the Commissioner, Rockville, MD, Bertram Walter Rein, Kristina Reynolds Osterhaus, Wiley Rein & Fielding, LLP, Washington, DC, for Plaintiffs.

Michael A. Humphreys, U.S. Attorney's Office, Drake Stephen Cutini, Barbara Stradling, U.S. Department of Justice, William Barnett Schultz, Zuckerman Spaeder, LLP, Washington, DC, for Defendants.


HENRY H. KENNEDY, District Judge.

Plaintiffs, Association of American Physicians and Surgeons ("AAPS"), Competitive Enterprise Institute ("CEI"), and Consumer Alert, bring this lawsuit to challenge the authority of the United States Food and Drug Administration ("FDA") to promulgate "Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products in Pediatric Patients" ("Pediatric Rule"), 21 C.F.R. § 201, 312, 314, 601, 63 Fed. Reg. 66, 632 (Dec. 2, 1998). Plaintiffs claim that the Pediatric Rule exceeds the FDA's statutory authority and that the Rule's promulgation was arbitrary and capricious. Plaintiffs thus petition this court for relief pursuant to the Administrative Procedure Act ("APA"), 5 U.S.C. § 701 et seq.

Before this court are the parties' cross-motions for summary judgment. Upon consideration of the parties' submissions and the summary-judgment record,1 the court concludes that defendants' motion for summary judgment must be denied and plaintiffs' motion for summary judgment must be granted.


The Federal Food Drug and Cosmetic Act ("FDCA"), 21 U.S.C. § 321 et seq., provides a systematic scheme for the approval of new drugs and new drug formulations intended to be marketed for use in interstate commerce. Under the FDCA, a new drug product cannot be marketed unless the FDA approves the product and determines that it is safe and effective for its intended use. See 21 U.S.C. § 355(a). When the FDA approves a drug, it approves the drug only for the particular use for which it was tested, but after the drug is approved for a particular use, the FDCA does not regulate how the drug may be prescribed. Thus, a drug that has been tested and approved for adult use only can be prescribed by a physician for her pediatric patients.

Because of the expense and difficulty in finding substantial pediatric populations to undergo tests, along with the ethical complications associated with testing new drugs on children, many drugs are tested for safety and effectiveness in adults only. As a result, even though there are many diseases and ailments that are common to both children and adults, physicians with pediatric patients2 often find their treatment options limited. Some physicians, forced "to choose between prescribing drugs without well-founded dosing and safety information or utilizing other, potentially less effective, therapy" respond by prescribing adult-approved drugs to children, but in a smaller dose. See Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products in Pediatric Patients, 62 Fed. Reg. 43, 900 (Aug. 15, 1997).

Prescribing adult-approved drugs to children is often referred to as going "off-label." An off-label use is the prescription of a drug by a doctor for a condition not indicated on the label or for a dosing regimen or patient population not specified on the label. Off-label use of pharmaceuticals appears to be "generally accepted" in the medical community. See Washington Legal Found. v. Friedman, 13 F. Supp.2d 51, 56 (D.D.C. 1998) vacated in part on other grounds, 202 F.3d 331 (D.C. Cir. 2000) (observing that "off-label use of FDA-approved drugs by physicians is an established aspect of the modem practice of medicine"); Buckman Co. v. Plaintiffs' Legal Comm., No. 98-1768, 2001 WL 167647, at *5 (U.S. Feb. 21, 2001).

While it is a common practice for physicians to prescribe to children pharmaceuticals only approved for adult use, by doing so, they can expose children to various hazards. Children may be given an ineffective dose or an overdose, and they face an increased risk of side effects. See 62 Fed. Reg. 43, 900, 43, 901. This happens because:

Correct pediatric dosing cannot necessarily be extrapolated from adult dosing information using an equivalence based either on weight . . . or body surface area. . . . Potentially significant differences in pharmacokinetics may alter a drug's effect in pediatric patients. The effects of growth and maturation of various organs, maturation of the immune system, alterations in metabolism throughout infancy and childhood, changes in body proportions, and other developmental changes may result in significant differences in the doses needed by pediatric patients and adults.

62 Fed. Reg. at 43, 901.

In the face of insufficient information about a new medication, pediatricians do not merely prescribe inexact doses, however. Physicians sometimes prescribe for their young patients older, less effective, but well-tested medication — as opposed to newer, more effective, medication that has not been subjected to rigorous study on pediatric populations. This practice keeps children from benefitting from state-of-the-art medication. See 63 Fed. Reg. at 66, 632.

In response to these concerns, in 1994, the FDA issued a regulation requiring manufacturers of marketed drugs to survey existing data and determine whether the data was sufficient to support pediatric use information on the drug's labeling. If so, the FDA required manufacturers to submit a supplemental new drug application seeking the FDA's approval of the labeling change. If the drug had not been sufficiently tested on children, the rule required the manufacturer to include in the product's labeling a statement to read: "Safety and effectiveness in pediatric patients have not been established." 21 C.F.R. § 201.57(f)(9)(vi).

Also in an effort to encourage pediatric testing, in 1997, Congress passed the Food and Drug Administration Modernization Act ("FDAMA"), Pub. L. No. 105-115, 111 Stat. 2296 (1997). This Act established a five-year experimental program to encourage pediatric drug testing. Under this Act, the FDA could request (but never require) manufacturers of new drugs to conduct studies on pediatric patients. Drug manufacturers that agreed to conduct these pediatric tests could receive six months of market exclusivity for their products. See 21 U.S.C. § 355a(a). Similarly, for already-marketed drugs, Congress required the FDA to publish a "list of approved drugs for which additional pediatric information may produce health benefits." § 355a(b). The statute also contained a requirement that the FDA report to Congress on the effectiveness and adequacy of this provision by January 1, 2001.3

Finding that the voluntary incentive provisions of FDAMA did not increase pediatric testing as much as the FDA had hoped, after proper notice-and-comment, the FDA issued the "Pediatric Rule" in 1998.4 See 63 Fed. Reg. at 66, 632; see also id. at 66, 639 (providing it "does not believe . . . that incentives alone will result in pediatric studies of some of the drugs and biologics where the need is greatest."); Letter from Hubbard to Rein, 11/1/2000 at 1 (hereafter "HHS Denial") ("the voluntary nature of the pediatric exclusivity incentive is likely to leave many drugs, age groups, and indications unstudied"); id. at 7 ("data indicate that voluntary efforts had not, by 1997, substantially increased the number of products entering the marketplace with adequate pediatric labeling"). This Rule's legitimacy is challenged here.

In application, the Pediatric Rule distinguishes new drugs from already-marketed drugs. Manufacturers of new drugs "may be required to submit an application containing data adequate to assess whether the drug is safe and effective in pediatric populations. The application may be required to contain adequate evidence to support dosage and administration in some or all pediatric subpopulations, including neonates, infants, children, and adolescents . . ." 21 C.F.R. § 201.23(a). This means, in effect, drug manufacturers may now be obligated to study their product on pediatric populations, even if the product is not explicitly marketed for children's use. In addition, the "applicant may also be required to develop a pediatric formulation for a drug product that represents a meaningful therapeutic benefit5 to such patients over existing therapies." Id.

The FDA presumes that sponsors will study all new drugs in pediatric patients unless the applicant can show that waiver is appropriate. Waivers are granted if: (1) necessary studies are impossible or highly impractical because, e.g., the number of such patients is so small or geographically dispersed; or (2) there is evidence strongly suggesting that the product would be ineffective or unsafe in all pediatric age groups.6 21 C.F.R. § 314.55(c)(2), 601.27(c)(2). In addition, an applicant may request a partial waiver of the above testing and development requirements if the applicant certifies that the product: (1) does not represent a meaningful therapeutic benefit for pediatric patients over existing treatments; and (2) is not likely to be used in a substantial number of pediatric patients. §§ 314.55(c)(2), 601.27(c)(2); 63 Fed. Reg. at 66,634. Partial waiver may also be available if a manufacturer can demonstrate that reasonable attempts to produce a pediatric formulation necessary for a particular age group have failed. See 21 C.F.R. § 314.55(c)(3), 601.27(c)(3).

For already-marketed drugs, the Pediatric Rule still applies, but it has a more narrow sweep. For such drugs, the FDA may still require a manufacturer to submit an application containing...

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