Premo Pharmaceutical Laboratories, Inc. v. US, No. 78 Civ. 5435(MP).

• Court: United States Courts of Appeals. United States Court of Appeals (5th Circuit)
• Writing for the Court: POLLACK
• Citation: 475 F. Supp. 52
• Parties: PREMO PHARMACEUTICAL LABORATORIES, INC., Plaintiff, v. UNITED STATES of America, Joseph A. Califano, Jr., Secretary of Health, Education and Welfare, and Donald M. Kennedy, Commissioner of Food and Drugs, Defendants.
• Docket Number: No. 78 Civ. 5435(MP).
• Decision Date: 27 July 1979

475 F. Supp. 52

PREMO PHARMACEUTICAL LABORATORIES, INC., Plaintiff,
v.
UNITED STATES of America, Joseph A. Califano, Jr., Secretary of Health, Education and Welfare, and Donald M. Kennedy, Commissioner of Food and Drugs, Defendants.

No. 78 Civ. 5435(MP).

United States District Court, S. D. New York.

July 27, 1979.

475 F. Supp. 53

Kirschstein, Kirschstein, Ottinger & Cobrin by David B. Kirschstein, New York City, Keller & Heckman by John S. Eldred and Deborah Shur Trinker, Washington, D. C., for plaintiff.

Robert B. Fiske, U. S. Atty., S.D.N.Y., by Janis Farrell and John M. O'Connor, Asst. U. S. Attys., New York City, for U. S. and H. E. W.

Jacqueline H. Eagle, Rockville, Md., for Food and Drug Administration.

OPINION

POLLACK, District Judge.

This is a suit by a manufacturer of pharmaceutical drugs against the Secretary of Health, Education and Welfare and the Commissioner of Food and Drugs, seeking a declaratory judgment that a questioned product manufactured by the plaintiff is not classifiable as a new drug and therefore may be freely sold and distributed without prior approval by the Food and Drug Administration ("FDA" hereafter). The FDA has initiated seizure actions against the product in four states and has threatened to seize it elsewhere. Thus there exists a justiciable controversy between the parties, and the Court has jurisdiction of the suit under 5 U.S.C. §§ 701-706; 21 U.S.C. § 301 et seq.; and 28 U.S.C. §§ 1331(a) and 2201.

Temporary relief by way of preliminary injunction was denied, and the issues were presented at a bench trial. For the reasons appearing hereafter the plaintiff, having established its right to relief by the requisite preponderance of credible evidence, will be awarded the declaratory judgment it seeks.

The plaintiff manufactures a tablet known as "Insulase," which is intended for use in the treatment of adults with mild to moderate chronic diabetes. The active ingredient in Insulase is the chemical chlorpropamide ("CPA" hereafter). CPA is also the active ingredient in a tablet manufactured by Pfizer Laboratories, Inc., "Diabinese," which is likewise used to treat diabetes. The inactive ingredients in Diabinese and Insulase, however, are not the same.

The plaintiff now sues for a declaratory judgment that Insulase is not a "new drug" within the meaning of section 201(p) of the Food, Drug and Cosmetic Act, 21 U.S.C. § 321(p). That section defines "new drug" as "any drug not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs as safe and effective for use under the conditions prescribed, recommended, or suggested in the labelling thereof. . . ." As noted above, if Insulase is not a "new drug" then it may be marketed without the prior approval of the FDA.

Diabinese was approved by the FDA over 20 years ago and has since been widely prescribed by physicians in the treatment of adult diabetics. The defendants concede that both Diabinese and CPA are generally recognized as safe and effective and that the inactive ingredients in Insulase are individually recognized as safe. The question, then, is whether the different combinations of inactive ingredients in Diabinese and Insulase make the latter a "new drug." Before addressing that question, it is necessary to set forth some terminology used in the analysis of drugs.

A drug product is a particular drug made by a particular manufacturer. Thus Diabinese and Insulase are different drug products,

475 F. Supp. 54

even though their active ingredients are the same. A drug product normally includes an active ingredient and various inactive ingredients, known collectively as excipients. Excipients may include binders mixed with the active ingredient to form a tablet, coatings, colorings, flavors, etc

The bio-availability of a drug product is the time within which the active ingredient reaches the site of its intended action in the body, together with the amount of the active ingredient that reaches that site. See 21 C.F.R. § 320.1(a). Bio-availability is measured clinically by administering the drug to a subject and measuring periodically thereafter the amount of the active ingredient present at the site of its intended action (or, if measurements cannot be taken at that site, then by measuring the amount of the active ingredient present in the bloodstream). The results of these measurements can be displayed on a graph in which the time since the drug was taken is shown on the horizontal axis and the measured amount of active ingredient shown on the vertical axis. If the results of each measurement are plotted on the graph, they will form a curve that begins where the two axes intersect (representing the time when the subject first took the drug and had none of the active ingredient in his bloodstream), then rises to a peak (representing the time when the subject had the greatest amount of the active ingredient in his bloodstream), and ultimately falls back to the horizontal axis (representing the time when the subject had eliminated all of the active ingredient from his bloodstream).

When such a curve is drawn it is possible to determine the three values by which the bio-availability of a drug product is measured, namely, C-max, T-max, and the area under the curve. C-max (which stands for maximum concentration) is the greatest amount of the active ingredient found to be present in the bloodstream during any one measurement. It is represented by the peak of the curve. T-max is the time after administration of the drug at which C-max occurs. The area under the curve is the area...