On September 30, FDA released a Draft Guidance to assist drug and biologic sponsors in preparing REMS. According to the guidance, FDA expects proposed REMS to have two sections: (1) a "proposed REMS section" describing the goals and elements of the REMS and (2) a "REMS supporting document" section explaining why the sponsor believes a REMS is necessary, how the identified elements will achieve those goals and how the effectiveness of the REMS will be assessed. The proposed elements should be specific (e.g., discuss the use of package inserts, medication guides, communication plans, training and expertise of prescribing healthcare providers, characteristics of patient population, limitation on healthcare setting, patient monitoring, etc.).

The Draft Guidance also addresses communicating with FDA regarding REMS. A proposed REMS may be included in the initial submission of an original or supplemental application, or as an amendment to an existing original or supplemental application. A proposed REMS submitted after approval and not associated with an existing supplement should be submitted as a new supplemental application.

Finally, as the guidance notes, there are statutory violations for failing to comply with an approved strategy. These violations can misbrand the drug product and subject the sponsor and "responsible parties" to civil monetary penalties and other liabilities (e.g., injunctions or criminal prosecution) associated with prohibited acts. What constitutes "compliance" with a REMS could well be the subject of controversy and possible litigation.