Return of the Scarlet Letter? AbbVie Petitions FDA to Require Biosimilar Labeling to Include Disclaimers and a Description of Data Differences

By Kurt R. Karst –      

It was just a few weeks ago that we noted in a post concerning FDA’s recently finalized guidance document on “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product” that the Agency removed from the 2012 draft version of the document any requirement that the labeling of a biosimilar biological product licensed under PHS Act § 351(k) indicate that it is biosimilar to a reference product, and also to call out whether or not it is interchangeable with a reference product.  As we commented then, “[w]hile such designations may not have made a biosimilar feel like Hester Prynne, it does seem that mandating such terms be present may have led to some shunning in the marketplace that is today’s town green.”

It seems that AbbVie Inc. (“AbbVie”) – which, interestingly, starts with the letter “A” – took note of the Scarlet Letter change as well.  In a June 2, 2015 Citizen Petition (Docket No. FDA-2015-P-2000) that popped up on regulations.gov earlier this afternoon (June 3rd, the same day the Federal Circuit heard Oral Argument in the Sandoz-Amgen “patent dance” case – which you can listen to and read about here, here, and here), AbbVie requests FDA to require the approved labeling for biological products licensed under PHS Act § 351(k) to contain (if applicable) certain statements and descriptions that would differentiate biosimilars from their reference product counterparts.  Specifically, AbbVie wants biosimilar labeling to include:

A clear statement that the product is a biosimilar, that the biosimilar is licensed for fewer than all the reference product’s conditions of use (if applicable), and that the biosimilar’s licensed conditions of use were based on extrapolation (if applicable);

A clear statement that FDA has not determined that the biosimilar product is interchangeable with the reference product (if applicable); and

A concise description of the pertinent data developed to support licensure of the biosimilar, along with information adequate to enable prescribers to distinguish data derived from studies of the biosimilar from data derived from studies of the reference product.

Biosimilars, which came about with the March 23, 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), “are not generic drugs and should not be labeled like generic drugs,” says AbbVie in its petition.  Including in biosimilar labeling the items above “is necessary to enable rational and informed prescribing decisions regarding these complex products, to avoid potentially unsafe substitution of biosimilars and reference products, and to combat widespread misconceptions among prescribers about biosimilars and their relationship to reference products,” writes the company.  Furthermore, without such differentiating statements and description, “biosimilar labeling will not reflect the unique licensure provisions established by the BPCIA and will be materially misleading in violation of the FDCA and FDA regulations.”  And, in what might be a signal of future litigation, AbbVie alleges that FDA’s “about-face” reversing, without explanation, what the Agency proposed in the 2012 draft guidance is a violation of the Administrative Procedure Act (“APA”).  (Though, keep in mind that the last time Abbvie – then Abbott Laboratories – petitioned FDA on the BPCIA back in 2012 – concerning Reference Product Exclusivity – we though a lawsuit might be looming – see our previous post here.  That didn’t happen – at least it hasn’t yet.)

Pointing to FDA’s March 6, 2015 approval of BLA 103353 for Sandoz Inc.’s (“Sandoz’s”) ZARXIO (filgrastim-sndz), a biosimilar version of Amgen Inc.’s NEUPOGEN (filgrastim), AbbVie says that FDA long ago made the decision to apply the “same labeling” requirement under FDCA § 505(j) (applicable to ANDAs) for small-molecule generic drugs to biosimilars licensed under PHS Act § 351(k):

Publicly available materials from FDA’s review of Zarxio confirm that FDA followed a “same labeling” approach.  According to the action package for Zarxio, in November 2013, Sandoz proposed and FDA agreed that the biosimilar and reference product labeling “should be essentially the same.”  In February 2015, FDA provided the labeling for Neupogen to Sandoz for use “as a template” in developing the labeling for Zarxio, and instructed Sandoz to track any changes made to the Neupogen labeling and provide annotations to explain and justify any such changes.  That is essentially what FDA regulations require of applicants seeking to market generic drugs under section 505(j).  Indeed, in the media briefing announcing the approval of Zarxio, the Director of the Office of New Drugs in the Center for Drug Evaluation and Research (CDER) acknowledged that the “approach” taken with respect to the labeling for Zarxio was “not that different from the approach . . . taken in the past . . . for generic applications.”  Consistent with that approach, the approved labeling for Zarxio is nearly identical to that of Neupogen . . . .

According to AbbVie, however, applying the FDC Act’s ANDA “same labeling” approach to to biosimilars is legally unsound.  AbbVie then ticks off the reasons why such an approach doesn’t comport with the law. 

“First, a ‘same labeling’ approach is flatly inconsistent with the BPCIA, which—unlike the [ANDA] provisions in section 505(j)—includes no ‘same labeling’ requirement and recognizes that biosimilars are different from their reference products. . . .” (Emphasis in original).  Here, AbbVie compares and contrasts the BPCIA and the FDC Act, noting, among other things, that the BPCIA specifically amended the FDC Act (at FDC Act § 505B, concerning required pediatric studies) to provide that a non-interchangeable biosimilar biological product “shall be considered to have a new active ingredient” (at least for purposes of FDC Act § 505B). 

“Second, a ‘same labeling’ approach to biosimilars would result in labeling that omits material information necessary for safe and informed prescribing, and would exacerbate, rather than dispel, misconceptions among prescribers regarding biosimilars.”  Here, AbbVie argues that applying a “same labeling” approach to biosimilars violates the FDC Act’s misbranding and misleading labeling provisions at FDC Act §§ 502(a) and 201(m), respectively.

Third, AbbVie argues that “FDA has not provided the reasoned explanation required by the APA for its decision to abandon the approach taken in the Draft Scientific Guidance, which stated that the labeling of a biosimilar product should disclose that the product is a biosimilar, the scope of its approval, and whether it has been found to be interchangeable, on the ground that this information is ‘necessary’ for informed prescribing.”  Going through the record of FDA meetings and comments leading up to and on the draft guidance, AbbVie asserts that “FDA’s decision to reverse course and adopt a same labeling approach for biosimilars is arbitrary and capricious.”

AbbVie’s petition includes a certification under FDC Act § 505(q), which was made applicable to petitions affecting pending Section 351(k) biosimilar applications under the 2012 FDA Safety and Innovation Act.  This is, by our count, the second citizen petition involving the BPCIA containing such a certification.  FDA denied the first 505(q) biosimilar petition earlier this year (see our previous posts here and here).  If FDA tags AbbVie’s petition as a 505(q) petition – which seems probably given the likley pending status of Section 351(k) applications at FDA that could be affected by the petition – then we can expect some sort of response within 150 days.