Tuesday, December 21, 2010

Different active ingredients, but pharmaceutically equivalent?

Pamlab L.L.C. v. Seton Pharmaceuticals, LLC, 2010 WL 4983170 (S.D.N.Y.)

Plaintiffs sought to stop certain claims by Seton about its drug Cavan-X. Under license from patentee-plaintiff Metabolite (the patent is for a composition treating, preventing, or reducing elevated metabolic levels), Pamlab markets Foltx, a medical food with 2 mg. of vitamin B12, 25 mg. of vitamin B6, and 2.5 mg. of folic acid (aka Folacin). Sublicensee-plaintiff Breckenridge markets Folbic as an "authorized generic" for Foltx. Folbic contains the same three active ingredients.

Defendant makes Cavan-X, which has the same amounts of vitamins B12 and B6, but 2.5 mg of folinic acid instead of folic acid. All three are prescription medical foods intended for people under treatment for hyperhomocysteinemia, a medical condition that increases the risk of artery disease.

Cavan-X’s initial label, until November 2010, didn’t use the term “folinic acid.” Instead, it listed the third active ingredient as Vitamin B9, followed by a footnote: "Vitamin B9 is a class of folates that includes folic acid and other vitamers-such as reduced folates." The revised label says: "Vitamin B9 is a class of folates that includes folic acid and reduced folates such as folinic acid."

Other relevant facts: pharmacists often consult one of two standard databases, First DataBank or Medi-Span, to find out whether there is one or more generic product that is pharmaceutically equivalent to a brand product. Generic manufacturers seeking substitution for brand name drugs inform database compilers on “new submission forms” that their generic products are “similar to” a particular brand and state the active ingredients. The list of active ingredients allows the compiler to figure out whether the generic is pharmaceutically equivalent to the brand name product: whether it has the same active ingredients in the same amounts. Compilers rely on generic manufacturers for this information. Products that are pharmaceutically equivalent are linked to one another in the databases.

In September 2010, defendant Seton submitted a new product submission form for Cavan-X, stating that the product was “similar to” Foltx, and that the ingredients were stated on the label. Medi-Span linked Cavan-X to Foltx and Folbic, and erroneously listed “folic acid” as Cavan-X’s third ingredient. Mid-November, Seton revised the label and communicated the revision to the two databases in these terms: "the Cavan-X label is being revised to state that vitamin B9 in Cavan-X is in the form of folinic acid. Ingested folic acid is metabolized into folinic acid." Medi-Span responded, "We have had a clinical team review this and it appears to be correct in our drug databases file."

In October, Plaintiffs moved for a TRO on patent infringement and Lanham Act grounds, which the court converted to a motion for a preliminary injunction. Plaintiffs then withdrew the request for injunctive relief on the patent claim because they had learned for the first time that Cavan-X didn’t have the same active ingredients. However, they proceeded with Lanham Act claims based on (1) misrepresentation of Cavan-X’s active ingredients on the label, and (2) an expiration date on the label not supported by adequate stability testing.

Falsity: plaintiffs argued that by failing to identify folinic acid as an ingredient, Seton made false statements about the active ingredients, as shown by Medi-Span’s treatment of Cavan-X. Plaintiffs also argued that vitamin B9 is folic acid, not folinic acid, while Seton argued that vitamin B9 includes folates, a family that includes both acids.

The court found that, though reference to folic acid might cause consumers to believe that Cavan-X contains folic acid, the label was not literally false to use the group label “vitamin B9” or “folates” to describe a specific member of that group. (But the initial label went further than using the group label—it then specified a member that was not an active ingredient; that seems like a good case for necessary implication.) The parties agreed that “folates” are a group of chemical compounds, including both acids. Moreover, for three of their own products, plaintiffs themselves designate "folate" as an active ingredient. The court found that, according to plaintiffs’ own expert, “vitamin B9” is used to refer to folates, not just folic acid.

In an evident caution to defendants, the court noted that Seton “could easily have properly identified the third active ingredient in Cavan-X as folinic acid. It appears that there was no reason for Defendant not to identify it as folinic acid, other than Defendant's desire to bolster its claim that Cavan-X is ‘similar to’--and thus should be ‘linked to’--Plaintiffs' products.” The footnote found that, for certain populations, the two acids have different impacts on the body, and “there remains more to be learned regarding possible differences between the two compounds.” Thus, a treating physician “would likely prefer to know that, when he/she prescribes either folic acid or folinic acid to a particular patient, the prescription will be filled as written,” and would likely expect to be able to rely on databases to state products’ specific ingredients. However, the Lanham Act does not require that level of specificity (at least, apparently, without proof of deception). This was not false by necessary implication, because “vitamin B9” and “folates” are ambiguous group labels susceptible to more than one reasonable interpretation.

The revised label now includes references to folinic acid and folic acid. Medi-Span will still apparently link Cavan-X to Foltx and Folbic. This makes the revised label less ambiguous than the original label.

Expiration date: Plaintiffs argued that the expiration date was an establishment claim indicating that sufficient stability data existed to support that date, even though the label says nothing about what kind of testing was performed. Seton argued that it relied on stability testing done on products similar to Cavan-X, and that it had begun accelerated and real time stability testing to verify the two-year expiration date, but it didn’t provide results to the court. Plaintiffs argued that performing stability testing on similar, but not identical, products didn’t meet the industry standard, and that results from the first two monts of Seton’s 3-month accelerated stability testing showed significant degradation, undermining its claim.

There is no FDA or other requirement that Cavan-X include an expiration date, but if one is included on a product like Cavan-X, then scientific justification using experimental data is required: that is, this is inherently an establishment claim.

Plaintiffs’ experts testified that industry practice rejects relying on stability data from “similar” products that don’t have the same active ingredients. Defendant’s expert witness, chief scientific officer for the company manufacturing Cavan-X for defendant, testified that she often used stability testing for similar products for an expiration date on a new product. The court found none of the experts experienced broadly enough to give dispositive testimony. With respect to expiration date testing for dietary supplements, the FDA found that views on the subject were far from uniform. Thus, plaintiffs failed to meet their burden of showing that the testing done was insufficient to support the expiration date given.

The court also rejected reliance on the first two months of accelerated stability testing, about which there was strong disagreement in any event. If the case proceeded to trial, more information might be available. Preliminary injunction denied.

1 comment:

cigaRHETT said...

Hi Rebecca;
You are right to point out that folinic should be disclosed on the label; however, it depends on the monograph or law that the indications follows. i can't recall exactly, but I think when I developed the cavan-x product I indicated prescription vitamin not medical food. or maybe i have that backwards.
anyhow, thanks for the insight.