There is a new proposed piece of legislation that appears to give approved holders of ANDAs the right to unilaterally revise their labeling to provide new safety information that is not found in the labeling of the reference listed drugs (RLDs). Over the years, many proposals have been put forward to change the way that generic drug labeling is updated, especially when the RLD is no longer marketed. The statutory requirement that the generic labeling must be the same as the RLD’s, with certain differences allowed by law, is clear; however, deciding which changes are appropriate and which are not is the purview of the FDA.
Well, a new piece of legislation, sponsored by Senators Van Hollen, Blumenthal, Brown, and Coons, consists of just sixteen lines of text (here) and appears to restart this conversation (see here).
Having generic drug holders unilaterally change their labels is a bad idea, which we have discussed in multiple previous various posts here, here (this one is very important toward understanding the entire issue), and here, among others.
However, what the sixteen-line proposed legislation seems to omit is a provision requiring that such labeling changes, for the addition of new safety information, ONLY be submitted in prior approval supplements (PASs) so the FDA can make assessments as to whether the proposed changes meet the FDA’s requirements and are accompanied by appropriate data supporting the proposed changes.
The interesting thing is that provisions are now in place for this to happen at the Agency and, thus, there is no reason for this newly proposed legislation, particularly without the PAS requirement. In one of the FDA’s draft Guidances, the Agency notes that it may entertain a PAS for certain proposed changes by an ANDA applicant or a CBE-0 if at the direction of the FDA. If a PAS is submitted, the FDA will review the proposed change and, if the Agency believes that the change should be made, it will notify all sponsors of the product that the specific change must be made to all of the same products, and it will prescribe a timeframe for making the change based on the significance of the change. The FDA already can and has utilized its authority under Section 505(o)(4) of the Act for mandated safety label changes (SLCs) and will direct sponsors to make such SLCs as it deems appropriate.
Why, then, is there still a perception that ANDA sponsors cannot submit SLC changes through PASs? In addition, the FDA is constantly monitoring adverse events for all drug products and has the authority and responsibility to require an SLC if it notes a problem. The FDA does make SLCs and publishes them on its webpage; generic sponsors are required to monitor the website and to make any changes. Permitting ANDA holders to unilaterally revise their labeling via CBE-0 supplements in order to include new or different safety information or warnings is a bad idea. While the concept of up-to-date information in labeling is clearly a good one, the chaos this would cause to statutory and regulatory requirements and restrictions on generic applicants would be overwhelming. Thus, allowing any submission other than a PAS should not be permitted.
Sometimes a seemingly slight change in legislation can trigger the law of unintended consequences and we could wind up with vastly different labeling, in terms of safety information, for every generic drug product on the market without the requirement for PASs clearly articulated. Allowing ANDA sponsors to make unilateral SLCs is an outcome with little or no advantage, especially if sponsors begin to over-warn solely to protect themselves from potential litigation, i.e., the everything-but-the-kitchen-sink approach, which does not serve patients well. The FDA must be the arbiter of any safety labeling changes for a generic drug as the Agency must deem such changes appropriate and necessary.
