Thursday, September 08, 2011

Expert testimony on meaning of term allowed in pharma case

Sciele Pharma, Inc. v. Brookstone Pharmaceuticals, LLC, 2011 WL 3844891 (N.D. Ga.)

Sciele sells the prescription prenatal vitamins Prenate Elite and Prenate DHA. Defendant Acella sells generic products, including competing prescription prenatal vitamins PNV and PNV-DHA.

Folate helps prevent certain birth defects. While most prenatal vitamins contain only folic acid, some women can’t metabolize folic acid. Prenate vitamins contain both folic acid and L-Methylfolate ("L-MTHF"), which is accessible even for those women.

Acella’s labels and package inserts say that PNV vitamins contain the same combination and amounts of folic acid and L-MTHF as Prenate vitamins. But the L-MTHF is delivered in a mixture with D-MTHF, the biologically inert isomer of MTHF. Sciele provided “considerable evidence” that PNV’s D,L-MTHF mixture is a different dietary ingredient than the substantially pure L-MTHF in Prenate. And there was some evidence that D-MTHF competes with L-MTHF, diminishing its effectiveness. Sciele thus argued literal falsity as well as misleadingness. It argued that, because defendants listed the same doses of identical ingredients, the products had been linked in various pharma databases, leading pharmacists to treat them as interchangeable and prescribe whatever’s cheaper. Prenate is more expensive than PNV, so pharmacists allegedly have been improperly filling prescriptions for Prenate with PNV.

Along with resolving various discovery disputes, the court declined to exclude Sciele’s evidence of product testing focused on the shelf life or active ingredient content of PNV vitamins. The complaint was broad enough to cover a claim of misleadingness based on the label’s shelf life and active ingredient content statements. Sciele had evidence suggesting that Acella didn’t test PNV vitamins to ensure that the vitamins maintain their labeled active ingredient concentration for 24 months, which is the labeled expiration date. This was “part and parcel of plaintiff's more general claim that PNV vitamins are not identical to PRENATE vitamins in strength or concentration, and do not deliver their active ingredients at the same rate and in the same amount as PRENATE vitamins.” Product testing evidence was obviously relevant.

Then there were the Daubert motions. The court refused to exclude the testimony of two Sciele witnesses, “leading experts in folate chemistry and stereochemistry respectively,” who were prepared to testify that the active ingredient in PNV vitamins was not properly described as L-MTHF and that the D,L-MTHF used in PNV vitamins was a distinct substance from the L-MTHF used in Prenate vitamins, with different physical, chemical and biological properties. (Awesomely, there is an entire journal called Chirality, and one of Sciele’s witnesses was its former EIC.)

The folate chemistry expert would offer relevant testimony based on his experience, training, and education, including testimony that the term LMTHF refers solely to the substantially pure isomer. Likewise, the stereochemistry expert would testify that D,L-MTHF and L-MTHF are different chemical entities that “must” be called by their distinct chemical names. Defendants argued that the experts were “career academics” with no practical experience in pharmacy or medicine, and thus not part of the relevant market. But they were well-qualified to offer opinions on “differences between, and nomenclature conventions governing, L-MTHF and D,L-MTHF.”

Note how the specialized field apparently allows expert testimony about what a term means, whereas with general consumer goods, you might expect a court to require consumer survey evidence. I think the court got it right here, but also that courts should also allow such evidence in the ordinary case.

Sciele also offered an expert on the issue of misleadingness to consumers, a licensed pharmacist with a doctorate in pharmacy administration who consults with pharma companies on marketing and evaluates pharma industry surveys. He conducted a survey of 150 pharmacists, who reviewed the package inserts for the parties’ products and were asked to determine how similar the two products were and whether they were appropriate for substitution. The expert, Dr. Reisetter, concluded that the labeling was misleading pharmacists to believe that the products were pharmaceutically equivalent.

Defendants argued that the study was fundamentally flawed because it relied on outdated package inserts and labels for PNV, because it lacked appropriate controls, because the sample size was too small, and because it used leading and biased questions. These were all issues that went to weight and didn’t defeat admissibility. (Other courts have excluded surveys without controls, so this is a risky one.) Among other things, the package inserts used in the survey were the ones Acella provided to the pharma databases when PNV was launched, leading them to link the parties’ products. This made them appropriate for the survey. Moreover, defendants didn’t change the package insert until after the survey was done. Dr. Reisetter also “persuasively explain[ed] the measures taken to control for bias in his survey,” and the court found that the questions were not leading or unduly biased, though it didn’t list the questions. And the sample size was large enough to provide meaningful results.

The court also accepted as an expert witness a former employee of First DataBank, one of the two leading pharmaceutical databases, who would testify among other things that, if the label or product information sheet had indicated that the active ingredient of PNV was D,L-MTHF rather than L-MTHF, the product would not have been linked to PRENATE. This was relevant and reliable based on her extensive experience. However, she wasn’t qualified to offer any opinion that requires specialized knowledge of stereochemistry in general, or of the chemical or physical properties of D,L-MTHF and L-MTHF in particular, so her proposed testimony that "[s]cientists have concluded that [d]efendants' product did not contain the stereoisomerically pure form of L-methylfolate" was improper.

Defendants also got their expert in on damages; Sciele’s criticisms went to weight and not admissibility. Also, the expert wasn’t required to audit Acella; he could use its financial statements without independently verifying the underlying supporting data.

On to various motions for summary judgment. Defendants argued that there was insufficient evidence to support a finding of falsity or misleadingness, and also argued FDCA preclusion. The court disagreed.

FDCA preclusion applies to attempts to use the Lanham Act to enforce the FDCA, or when a Lanham Act claim strays too close to the FDA’s exclusive enforcement domain. The key factors are the extent of the plaintiff’s reliance on the FDCA as a basis of its claim or the extent to which the court would be required to interpret or apply the FDCA or FDA regulations to decide the claim. Here, however, Sciele was relying on industry and market evidence to show that the ingredients were distinct, and wasn’t arguing about the meaning of any FDCA provision. The Lanham Act was designed to cover the conduct alleged: the false description of a product.

The court also found sufficient evidence of literal falsity, as detailed above (additionally, the American Chemical Society and the Joint FAO/WHO Expert Committee on Food Additives have recognized that L-MTHF and D,L-MTHF are distinct dietary ingredients, and the FDA has accepted a New Dietary Ingredient Notification distinguishing the substantially pure form of L-MTHF from D,L-MTHF). A jury could find literal falsity from this evidence.

Likewise, a jury could find misleadingness based on the survey evidence. Defendants argued that they were entitled to summary judgment because of a disclaimer on PNV’s label expressly disavowing any claims of equivalence or generic status. “This argument is disingenuous, at best. There is an abundance of evidence in the record to suggest that defendants intended to profit from the substitution that occurs as a result of PNV's linkage to PRENATE in the pharmaceutical databases. Based on that evidence, the jury might reasonably conclude that Acella's disclaimer was not intended to, and in fact did not, discourage substitution.”

However, the court declined to award Sciele partial summary judgment on literal falsity. Sciele argued that PNV simply didn’t contain the active ingredient listed on its label, L-MTHF, and also pressed its shelf-life claims based on Acella’s lack of testing to ensure that PNV vitamins maintain their active ingredient concentration over the course of their labeled two-year shelf life.

The court held that the evidence of literal falsity was not conclusive; defendants identified enough flaws in Sciele’s case that a jury might find in their favor, and they offered evidence that L-MTHF was reasonably susceptible to more than one meaning and understood by the relevant industry to refer to the L isomer of MTHF, “whether it is in its substantially pure form or combined in a mixture with D-MTHF.” This included testimony from an OB/GYN who regularly prescribes folate supplements and from a practicing pharmacist.

As for the shelf life/content claims, Sciele relied on the proposition that the expiration date was an establishment claim. An establishment claim is “an affirmative promotional claim about testing,” but Acella didn’t make any affirmative representations about testing. (I think an expiration date, especially on a prescription pharmaceutical, is likely to necessarily imply scientific supporting data. And the classic establishment claim cases point out that establishment claims can be made without the words “tests prove,” for example by showing actors in white coats acting like doctors.) To prove its shelf life/content claims, Sciele would have to show that PNV vitamins don’t have a two-year shelf life or contain the advertised concentration during that two-year period. It hadn’t done so on this record, and there was some substantiation for the labeling: defendants offered testimony that the expiration date was based on the expiration date of the raw materials plus the manufacturers’ knowledge of similar raw materials, confirmed by manufacturers’ certificates of analysis. Acella also accounts for natural degradation over time. These procedures didn’t meet Sciele’s own internal standards, but there was evidence from which a jury could conclude that Acella’s testing procedures were acceptable in the industry.

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