FDA Denies Vanda’s Citizen Petitions Regarding the Need for Braille Labeling for Tasimelteon Generics

August 18, 2023By Mark A. Tobolowsky

In January 2023, Vanda Pharmaceuticals, Inc. (Vanda) submitted two interesting and substantially similar citizen petitions (Docket Nos. FDA-2023-P-0313 and FDA-2023-P-0344) regarding its product Hetlioz (tasimelteon).  Vanda requested that FDA revoke the approval of Apotex’s and Teva’s generic versions of Hetlioz on the grounds that the generic tasimelteon products did not meet the statutory “same labeling” requirement for generic drugs found in 21 U.S.C. § 355(j)(2)(A)(v).  This statutory provision requires generic drugs to have the same labeling as that approved for the listed drug “except for changes required because of differences approved under a [suitability petition, allowing for certain differences] or because the new drug and the listed drug are produced or distributed by different manufacturers.”  FDA regulations, at 21 C.F.R. § 314.94(a)(8)(iv), interpret these provisions to also allow changes due to an aspect of labeling protected by patent or exclusivity.

The difference at issue here is the fact that Vanda’s Hetlioz product includes braille writing on its packaging, with some accompanying language (“Do not cover Braille”), and the generic products’ labeling does not.  This matters particularly strongly in this case, Vanda argued, because the generic products are approved for only one indication, a sleep disorder that disproportionately occurs in blind individuals.  Vanda’s Hetlioz was, in fact, the first FDA-approved drug product to include braille labeling.  Nor did this difference meet any of the statutory or regulatory exceptions to the “same labeling” requirement, Vanda argued.  As such, Vanda’s citizen petition stated that these approvals are “clearly erroneous under the FDCA and agency regulations and will put . . . patients in harm’s way.”  The citizen petition requested FDA revoke the approvals and recall the product in the marketplace.

FDA responded in late July, denying Vanda’s petitions.  FDA’s response stated that the two generic sponsors had submitted side-by-side comparisons of the labeling for their products as compared to the reference listed drug (RLD) Hetlioz, noting the differences Vanda raised in its petition.  FDA concluded at that time that these differences still met the “same labeling” requirement due to the “different manufacturer” exception.

FDA’s petition response included several grounds on which it based its decision to deny Vanda’s citizen petitions.  First, FDA noted that the Agency has interpreted the “different manufacturer” exception broadly, on a case-by-case basis, and listed various examples of when they have done this in the past.  Such differences have included different disposal methods in the labeling, a different ingredient safety warning, and a situation where a generic did not include halal and kosher certifications in its labeling where the RLD labeling did.  Other differences have included differences in font, color, trade name, and other trade dress.  Thus, FDA’s response argued that Vanda’s interpretation of the exception is inconsistent with FDA’s.

Secondly, FDA’s response stated that the only pieces of information that were repeated in braille in Vanda’s container labeling were the proprietary name and the strength of the drug product.  As the proprietary name is not generally included in generic drug labeling, which is interpreted as an acceptable difference, this leaves only the strength as the information that would be expected to appear in generic labeling.  FDA also disagreed that the inclusion of the strength or a product name was necessary for the safe and effective use of the drug product, noting that this was a voluntary addition to the labeling by Vanda, not required by the Agency during review.  FDA did request a Label Comprehension Study during Hetlioz’s review to evaluate whether the braille might introduce a new risk of medication errors, which Vanda conducted, but, the response stated that this does not establish that the braille is necessary for the safe and effective use of the product.

Moreover, other information, such as dosing instructions and warnings, were not presented in braille.  FDA argued that this rebutted Vanda’s argument regarding the necessity of the braille to the safe and effective use of the product.  FDA stated in its response that there is not sufficient support for a claim that the absence of braille will lead to medication errors for the patients at issue, nor have there been any such reported to date.

Finally, FDA’s response stated that the accompanying language (“Do not cover Braille”) would be acceptable to omit, given that it might cause confusion where there is no braille on the generic product labeling, and this would not violate the “same labeling” requirement.

Vanda has a history of challenging FDA statutory interpretations in court, so it’s possible this is not the last we hear of this issue.  However, we will have to wait and see what happens.