Posted 11 March 2014
By Alexander Gaffney, RAC
The US Food and Drug Administration (FDA) is defending itself against critics of its proposed generic drug labeling rule, which would change the way generic drug manufacturers are able to update their labels to reflect emerging or established safety risks.
Regulatory Focus has written extensively about the proposed rule, including its legal background, initial calls by legislators for reform, FDA's early plans for a rule change, the reaction of legal experts to the rule, the reaction of the generic drug industry, FDA's extension of the rule's comment period, the reaction of conservative legislators, the generic drug industry's estimates of the rule's costs, a proposed House Energy and Commerce Committee hearing on the rule, and recent jostling between opponents and proponents of the rule.
In short, FDA's rule would allow generic drug manufacturers to temporarily update the labels on their products if they were made aware of new safety issues that might pose a risk for consumers. Those updates, which would be done through the submission of a Changes Being Effected (CBE) Zero-day (CBE-0) application, would allow the companies to immediately make changes while waiting for FDA and the owner (if they still existed) of the original reference listed drug (RLD) to decide if the change was necessary.
FDA's intent, it said, was to permit differences to exist between the NDA and the ANDA on a "temporary basis."
FDA Responds at Last
Since the rule's release, proponent and opponents of the rule-and especially the latter-have been outspoken about it, talking about its effects and whether or not it is legal to implement.
But all the while, one voice has been curiously silent: the voice of FDA.
Late last week, FDA made what appeared to be its first major defense of the proposed rule.
In a 26 February 2014 letter-reported by Kurt Karst of FDA Law Blog and The Pink Sheet-FDA responded to questions raised by Republican legislators, providing a more nuanced glimpse into the agency's rationale for proposing the rule.
For regulators, the rationale for the rule comes as the generic drug industry has continued to mature, expand and grow. "Tension has grown between FDA's requirements that a generic drug have the same labeling as its reference-listed drug (RLD)," FDA wrote, and the need for generic drug manufacturers to be able to "ensure that the labeling is accurate and up to date."
This is particularly evident in cases where the original holder of the RLD-the original drug that is the source of comparison for the generic drug-has gone out of business or no longer markets the drug. In such cases, the generic drug manufacturer cannot update the label, and neither can it petition the RLD holder to update its own label.
FDA also took issue with the generic manufacturing industry's claim that confusion would emerge if differences were to temporarily exist on drug labels. Such temporary differences already routinely exist, usually when a sponsor updates the labeling of an RLD, and generic drug sponsors must then update their labels as well.
While FDA "advises that this update should occur at the very earliest time possible," the agency has found that there is "often a delay" in the occurrence of that update. The new rule, it said, would actually reduce this delay by coordinating changes more closely.
However, FDA largely skirted pointed questioning from legislators about the accuracy of its cost projections. FDA said it thought the rule would cost between $4,237 and $25,852 per year, and that it would receive approximately 20 CBE-0 labeling change applications. Some in industry have said this estimate is far below what the actual costs would be. In its response to legislators, FDA simply pointed to its existing analysis of the rule and implied that it stood behind this analysis.
However, FDA did concede one interesting point in its letter: At present, generic companies are able to propose labeling changes to FDA in light of new safety information. FDA said information on the frequency of this process was not readily available, and that it could not provide the legislators with those statistics. Regulators said the new rule, however, would create an obligation, unlike the currently-voluntary process.
FDA also claimed that the CBE-0 process was necessary to make prompt updates to drug labels. The Prior Approval Supplement (PAS) process would take too long, it added.