REMS and ANDAs – An “Unintended” Consequence of Improved Safety
Written by Garth Boehm December 14, 2014
REMS stand for Risk Evaluation and Mitigation Strategies. FDA has a long history of systems for informing on and managing drug safety issues. One aspect of this issue is the use of drug product specific strategies aimed at improving safe use of drugs with potential safety issues. These can include toxicity, serious side effects, effects on a fetus, and other safety issues. REMS came into being following several previous versions of individual safety strategies (broadly referred to as Medication Guides) in September 2007 following the passage of the FDA Amendments Act (FDAAA). Since that time, REMS have become an important part of FDA's drug safety programs.
A REMS has five elements. I want to focus, however, on only one of those elements. This element is described as follows.
Elements to Assure Safe Use (EASU) – These are strictly controlled systems or requirements put into place to enforce the appropriate use of a drug. Examples of EASUs include physician certification requirements in order to prescribe the drug, patient enrollment in a central registry, distribution of the drug restricted to certain specialty pharmacies, etc.
The intention of EASU is to prevent inappropriate or uncontrolled prescribing of a drug product with potentially serious safety issues without the necessary “safety elements” being in place. While this is a laudable goal, it has had a (presumably) unintended consequence of preventing generic companies from obtaining samples of brand products which have a REMS with an EASU included. Brand companies refuse to sell brand product to generic companies because they do not meet the requirements of the EASU. In reality there is no risk here, the issue is using the EASU to prevent generic companies developing and filing generic equivalents to the brand product. Some of the requirement for brand samples is for in vitro testing, such as dissolution studies, and some is required for bioequivalence studies or possible clinical equivalence studies. In some instances there is already posted guidance on the required in vivo studies.
This guidance title is a little more descriptive than usual for a guidance, and is self-explanatory. As the title says, the guidance tells generic sponsors how to get a letter from FDA stating, in effect, that they comply with the EASU requirements. The purpose of this letter is to remove the last (and very flimsy) excuse for a brand company not selling brand product to a generic company for the purpose of developing a generic equivalent. While this will not guarantee that the brand company will sell the RLD, it should provide a very strong basis to press a case against brand companies that refuse to sell product. Ultimately, if this guidance does not change this anti-trust behavior, a legislative fix may be required. We will have to see what happens in these instances over the next year or so.
