NAD Takes a Crack at Bioavailability

By Cassandra A. Soltis –

In an advertising challenge brought by the Perrigo Company (“Perrigo”), the National Advertising Division (“NAD”) of the Better Business Bureau recommended that Pharmavite, LLC (Pharmavite) refrain from making several claims for its Nature Made® Prenatal + DHA Liquid Softgel Vitamins until the company completes competent and reliable testing that establishes the bioavailability of the folic acid in the product.  Advertising for the Prenatal Vitamin included FDA’s authorized folic acid/neural tube defects health claim and a statement that the product was formulated for “easy absorption.” 

Perrigo alleged that Pharmavite could not substantiate the claims because the product does not adhere to the U.S. Pharmacopeia (“USP”) standard titled “Disintegration and Dissolution of Dietary Supplements, 2040,” which determines whether a dietary ingredient is bioavailable.  Dietary supplements bearing the folic acid/neural tube defects health claim must meet this standard in order to bear the health claim, unless the standard is not applicable, in which case “the folate in the dietary supplement [must] be shown to be bioavailable under the conditions of use stated on the product label.”  21 C.F.R. § 101.79(c)(2)(ii)(B).

According to Perrigo, it tested Pharmavite’s Prenatal Vitamin using the pertinent USP standard and found less than 12.5% of the labeled amount of folic acid had dissolved after six hours.  (The USP’s standard requires that at least 75% of the labeled amount dissolve within one hour under the intended conditions of use.)  Perrigo explained that fat or oil-based components, such as DHA, are expected to inhibit the absorption of water soluble vitamins, such as folic acid.  Accordingly, Perrigo asserted, it is unlikely that Pharmavite’s product can pass a dissolution test of any kind.

Pharmavite responded that its Prenatal Vitamin product did meet the pertinent USP Standard for softgel dietary supplements, which is the rupture test.  Pharmavite explained that, because its product passed the rupture test, the product was bioavailable and the claims were substantiated.  Even so, Pharmavite conducted more testing by incorporating an additional dissolution step, which used a surfactant to determine the availability of the contents of the softgel.  Pharmavite stated that the results from this testing further supported the bioavailability of the product.

The NAD disagreed with Pharmavite, essentially finding that neither USP standard could show that the product was bioavailable.  NAD based its decision on an article that appeared in the Pharmacopeial Forum, which explained that the rupture test may be inadequate on its own when the contents of a softgel are dispersed as a suspension or emulsion (i.e., an oil).  The article suggested that dissolution conditions that mimic the in vivo environment may be helpful in these circumstances.  Because Pharmavite’s additional testing did not mimic the in vivo environment, NAD concluded that Pharmavite did not show that the folic acid in its softgel Prenatal Vitamin was bioavailable. 

Pharmavite agreed to discontinue the challenged claims until it conducts testing that recreates the in vivo setting.  This case may have repercussion for similar products that combine water soluble vitamins with oil-based components.