Obtaining Samples for BE Testing for Products with Restricted Distribution Systems or REMS

The generic industry has been having a hard time (to say the least) in obtaining samples of certain Reference Listed Drugs (RLDs) that have Risk Evaluation and Mitigations Strategies (REMS) with elements to assure safe use (ETASU) upon which to conduct the necessary bioequivalence (BE) studies to support ANDA approval.   Today, FDA has published a Draft Guidance entitled, “How to Obtain a Letter from FDA Stating that Bioequivalence Study Protocols Contain Safety Protections Comparable to Applicable REMS for RLD” (here).

The Guidance outlines the steps that an applicant should take to in order to obtain such a letter, specifically, for RLD products with REMS that contain ETASU that otherwise would preclude the ANDA applicant from obtaining those for BE testing (e.g., products that may be under restricted distribution systems).  Once the required information is submitted to FDA (via a BE protocol, and discussion of patient protection that is at least as good as that outlined in the REMS), the FDA will review it and make a determination that either more information is necessary or that the applicant’s proposal meet all requirements.  If the protocol meets FDA requirements, the FDA will send a letter to the applicant acknowledging that fact.  In addition, they will send a similar letter to the RLD application holder to inform them that patient protection can be assured under the proposed BE protocol.  The ANDA applicant must first provide OGD a release letter (sample copy is included at the end of the Draft Guidance at the link above) which allows the FDA to contact the RLD holder.

FDA states that this letter is on no way a legal requirement, but what they don’t say is that (at least at this point in time), the RLD holder is under no obligation to release, sell or otherwise provide BE samples to the ANDA applicant, even if the FDA sends them this letter.   We understand that the Federal Trade Commission (FTC), as well as some members of Congress, is looking into this issue.

There are two sides to this story – one is that generic companies feel the RLD holder’s actions are a restraint of trade because they preclude the generic company from being able to prepare an application that can ultimately gain approval and compete with the RLD.  In addition, generic companies point to a section of the Food and Drug Administration Amendments Act (FDAAA) that precludes an innovator from using the provisions of a REMS to block generic competition (“No holder of an approved covered application shall use any element to assure safe use required by the Secretary under this subsection to block or delay approval of an application under section 505(b)(2) or (j) or to prevent application of such element under subsection (i)(1)(B) to a drug that is the subject of an abbreviated new drug application.”)  The innovators argue that the constitution of the United States precludes forcing them to sell their product to someone they chose not to sell to.

So, you can go through the process, and FDA can send you and the RLD holder a letter, but typically, the innovators so far have indicated they are not willing to make the sale.  This entire issue will likely be played out by the actions that FTC may take, legislation the Congress may pass and then ultimately how the courts interpret any new lay of FTC action.  Good luck, but don’t expect this issue to be resolved any time soon.