Regulatory Focus™ > News Articles > With Competition Close on the Horizon, Suboxone Manufacturer Files Challenge With FDA

With Competition Close on the Horizon, Suboxone Manufacturer Files Challenge With FDA

Posted 09 September 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) should not approve the application submitted by a generic competitor to Suboxone (buprenorphine), a drug used to treat opioid addiction, through the 505(b)(2) regulatory pathway, argues a new Citizen Petition filed by law firm Hyman, Phelps & McNamara (HPM).


Under current regulatory policy, pharmaceutical products generally obtain approval from FDA through three distinct regulatory pathways:

  1. New Drug Approval (NDA) applications under section 505(b)(1) of the Federal Food, Drug and Cosmetic Act (FD&C Act), which is used for new molecular entities or drug products for which the sponsor has the right of reference to the data used to support approval (i.e. the sponsor conducted or purchased the clinical and non-clinical data).
  2. Abbreviated New Drug Approvals (ANDAs) under section 505(j) of the FD&C Act, which is used for generic drug products seeking approval as a referenced listed drug (RLD) under FDA's Orange Book listings. Such drugs must undergo bioequivalence (BE) and other non-clinical equivalence testing, but are generally exempted from having to conduct new clinical trials under the theory that if they are chemically identical (within specified parameters) to a drug approved under an NDA, they are as safe and effective as the original drug as well.
  3. NDAs under section 505(b)(2) of the FD&C Act, which is used for drug products which are significantly similar to an existing NDA, but may use an alternate route of administration or have other changes that would render un-approvable via the 505(j) pathway. Under the 505(b)(2) pathway, companies reference a competitor's data which they do not have the right of reference to, but in most cases also must conduct limited clinical testing in order to prove the efficacy and safety of their new formulation.

The Citizen Petition

HPM explains the history of Suboxone in its Citizen Petition, noting its original approvals in October 2002 for two now-withdrawn products under NDA #20-733. In August 2010, FDA approved two new formulations of the drug, followed by two additional strengths in August 2012.

Moreover, the drugs are still protected by two patents, HPM said: Patents #8,017,150 and #8,475,832, which respectively cover the qualities of the product that ensure product consistency and potency.

In August 2013, FDA received a 505(b)(2)-based NDA application from BDSI for a "buccal film" buprenorphine/naloxone product (Bunavail) intended to treat opioid dependence. BDSI's product is reportedly a small, bioerodible polymer film that is absorbed into the body through the mucosal membranes of the cheek.

Per BDSI's statement, its NDA filing included bioequivalence, safety and tolerability data conducted by the company to assess the qualities of the product and the safety of switching subjects from Suboxone film or tablet products to Bunavail.

HPM: Notification Procedures Weren't Followed

HPM raises two points of contention with FDA's approval of this product:

  • BDSI's product "should be required to identify the sublingual film product approved in NDA #22-410 (Suboxone) as the listed drug."
  • BDSI "must be able to demonstrate that any genotoxic or potentially genotoxic impurities associated with naloxone are limited appropriately."

To the first point, HPM notes that per the 505(b)(2) statute in the FD&C Act, BDSI is required to notify the drug's NDA holder (Reckitt Benckiser Pharmaceuticals) that its data is being referenced in the 505(b)(2) NDA filing.

Further, BDSI is required to certify that both marketing- and patent-based exclusivity provisions for the original listed drug have expired.

"Specifically, the applicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or, (iv) the listed patent is invalid or will not be infringed by the new product," HPM explained. These notification methods are more commonly known as Paragraph Certifications (e.g. Paragraph IV Certification), and are often the precursor to patent litigation between the two companies.

In this particular case, HPM claims BDSI is attempting to make an "end run" around the patent protection process by claiming that Reckitt Benckiser's patents held on its Suboxone listed drugs applied only to the sublingual film, and not to BDSI's buccal film.

Per BDSI's press release:

"If approved, BUNAVAIL will be the first dosage form for the treatment of opioid dependence that does not require under the tongue (or sublingual) administration.  Utilizing the BEMA drug delivery technology, BUNAVAIL films adhere to the inside of the cheek and dissolve quickly.  By keeping BUNAVAIL in contact with the mucosal surface, our data demonstrates that buprenorphine absorption is optimized and provides comparable plasma concentrations of buprenorphine to Suboxone with considerably lower doses."

HPM argues that in this case, the sublingual Suboxone film is the "most similar alternative," and per FDA policy (as established in prior Citizen Petition responses) should be the referenced product in the Orange Book.

HPM notes FDA has the authority to "refuse to file a 505(b)(2) NDA that does not identify the appropriate listed drug."

HPM's petition also includes a relatively short paragraph arguing for FDA to "re-affirm that any buprenorphine/naloxone product will be subject [to impurity requirements]" established for the product at the 0.01% limit. No explanation for this request was given, though its inclusion presumably denotes another line of attack for HPM should its Citizen Petition fail.

HPM Citizen Petition

BDSI Press Statement

Suboxone Website

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