Opinion ID: 545552
Heading Depth: 2
Heading Rank: 2

Heading: Labeling and Marketing of E-Ferol

Text: 15 In August 1983, Carter and Madison prepared the labeling for E-Ferol. Carter wrote the first draft of the package insert that was to accompany the product. He used the E-Ferol IM label as a model even though he knew the new product would have an intravenous route of administration. The Indications section of the insert set forth uses of E-Ferol as a nutritional supplement, but at Madison's request, Carter put a reference to RLF in the insert's Clinical Pharmacology section. Carter also accepted Madison's suggestion that the dosage recommendation in the label be the same as the E-Ferol IM dosage that Madison understood was being used by physicians to treat RLF (25 to 50 milligrams), and included that recommended dosage in the draft insert he sent Madison. 16 Madison made revisions to E-Ferol's package insert, including additional references to RLF, all of which he sent to Carter for comments. The reference to RLF in the clinical pharmacology section of the final draft of the insert read as follows: Reports in the literature indicate that substantial doses of Vitamin E will reduce the severity of retrolental fibroplasia in neonatals, which are administered oxygen because of their low weight, under 1500 grams.  11 The asterisk referred the reader to the insert's References section, in which Madison had placed a list of scientific articles pertaining to the use of vitamin E as a treatment for RLF. There was nothing in the labeling that indicated E-Ferol had never been tested for safety and effectiveness. 17 In a memorandum dated July 20, 1983, Madison advised Hiland that the new intravenous vitamin E product would be used for nutritional purposes and [f]or Retrolental Fibroplasia (RLF) for which the dose is 25 mg. every day. (We cannot label it for this use--it would make it a New Drug). Madison also forwarded Hiland an August 8, 1983 memorandum from Samuel Fainberg, OJF's technical and regulatory consultant, in which Fainberg stated, I do not believe that legally we can make a claim that Vitamin E is effective against Retrolental Fibroplasia if given to infants. This will require a[n] NDA [new drug application] approval for the use of Vitamin E as a drug. On August 15, 1983, Madison sent Hiland a memorandum discussing the labeling for E-Ferol and a marketing plan for the product. In this memorandum, he told Hiland that the package insert made reference to the product's use for RLF. Madison then explained, We have to be careful how we show the 'Indications' for RLF. See insert; we list it under Clinical Pharmacology. According to Madison's testimony, he included with the memorandum a copy of the draft insert for Hiland to review. Hiland claimed at trial that he did not read E-Ferol's package insert until January 1984. 18 In September 1983, Hiland approved the marketing campaign for E-Ferol, which consisted of a mass mailing of Dear Doctor letters accompanied by a brochure with a copy of the package insert on the reverse side. These promotional materials were mailed in late October 1983 and again in January 1984 to approximately one thousand directors of neonatal intensive care units. This group was chosen because they were involved in the treatment of RLF. Nothing in the promotional materials indicated that E-Ferol had never been tested to determine whether it was safe and effective for the treatment of RLF in premature infants. 19 At trial, physicians and pharmacists testified that based on E-Ferol's labeling, they believed the product was being promoted for the treatment of RLF in premature infants. In addition to the references to RLF, the high dosage recommended in the labeling was a clear indication to them that E-Ferol was to be used for RLF because the dosage was well above any possible nutritional needs of premature infants. Pharmacists and physicians also testified that they were led to believe E-Ferol had been tested and proven as safe for use in premature infants, especially because the labeling contained no warnings or suggestions to the contrary and it was extremely unusual to see a product specifically labeled and marketed for use in premature infants. They testified further that they assumed E-Ferol had been approved by the FDA because it was targeted for the treatment of RLF in premature infants and had an intravenous route of administration, which distinguished it from the other single-entity vitamin E products on the market. 20