Yesterday, the FDA issued two draft guidance documents titled Development of a Shared System REMS (here) and Waivers of the Single, Shared System REMS Requirement (here). As the names may imply, if a shared system is possible, then that is the way an applicant should go, but if there are insurmountable hurdles to a shared system, then a waiver from the FDA may be possible.
There has been a lot of controversy regarding the Risk Evaluation and Mitigation Strategy (REMS) requirements, especially regarding REMS programs that are covered by intellectual property or when the innovator is reluctant to cooperate with generic applicants to develop a shared system. Such problems can delay the entry of a generic product when there is a REMS with Elements to Assure Safe Use (ETASU).
As stated in the Waivers of the Single, Shared System REMS Requirement guidance at 5:
“The Food and Drug Administration Amendments Act of 2007 (FDAAA) created section 505-1 of the FD&C Act, which authorizes FDA to require a REMS if FDA determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks.”
As stated in the Federal Register notice (here) announcing the Waivers of the Single, Shared System Requirement
“Section 505-l(i)(l)(B) of the FD&C Act requires that a holder of an ANDA under section 505(j) use a “single, shared system” with the RLD for any ETASU, unless FDA waives this requirement. The statute permits a waiver of the SSS requirement if FDA finds that (1) “the burden of creating a [SSS] outweighs the benefit of a single, system, taking into consideration the impact on health care providers, patients, the applicant for the [ANDA], and the holder of the reference drug product,” or (2) an aspect of the ETASU for the applicable listed drug is claimed by an unexpired patent or trade secret and the ANDA applicant certifies that it sought a license for use of the aspect, but was unable to obtain one. If a waiver of the SSS requirement is granted, the ANDA may use “a different, comparable aspect of the [ETASU],” instead of participating in a SSS with the RLD.”
There are obvious benefits to the use of a shared REMS system for both the applicants and health care providers, and these are explored and outlined in the two documents. However, the road to getting to a shared system may involve long and complex negotiations that may or may not be successful. To that end, if things don’t go well, an ANDA applicant can request a waiver from the use of a shared REMS, or, for that matter, the FDA can issue a waiver on its own initiative. If a separate REMS is to be developed, the FDA will, on a case-by-case basis, evaluate the components of the separate REMS and the applicant’s proposed ETASU to determine whether they are comparable to the innovators.
The two documents appear to be complimentary in nature. To me, the two guidance documents for developing a shared REMS and the waiver provisions signal that the FDA is willing to move away from a shared REMS, despite its benefits, if it appears that a significant delay in the entry of a generic product into the market could occur if negotiations between the parties or intellectual property considerations make the possibility of a shared system unlikely. At least now there is clarity as to how to proceed for each eventuality.