The US Food and Drug Administration's (FDA) Office of Generic Drugs (OGD), part of its Center for Drug Evaluation and Research (CDER), is out with the new policy that aims to clarify how its staff should implement a relatively new statutory provision that permits the agency to approve generic drugs even when labeling changes are happening with its comparator product, the reference listed drug (RLD).
The section in question, 505(j)(10) of the Federal Food Drug and Cosmetic Act (FD&C Act), was passed as part of the Patient Protection and Affordable Care Act (PPACA), and allows FDA to approve a generic application submitted under the 505(j) pathway-the pathway most often used by generic drug products-even if its reference listed drug ( RLD) is undergoing a simultaneous label change.
Under prior federal law-and a considerable amount of legal precedent, such asPliva v. Mensing-generic drug products must exactly match the RLD, even in cases where the circumstances might warrant an update, such as safety problem only discovered by the generic manufacturer.
Under the new policy, a Manual of Policies and Procedures (MAPP 5230.3, ) document posted on 13 February 2013 by FDA, the agency can approve those ANDA applications if-and only if-the ANDA applicant agrees to submit revised labeling corresponding to the RLD labeling changes within 60 days of notification of the change.
The MAPP outlines a three-part test that all ANDA sponsors must meet under the unique circumstances:
- "The approval of the RLD's labeling revision is made within 60 days before the expiration of a listed patent, an exclusivity period, or a 30-month stay delaying ANDA approval."
- "The approved revision to the labeling of the RLD does not include a change to the 'Warnings' section (the physician labeling rule format consolidates the "Warnings and Precautions" sections)."
- "FDA has determined that the continued presence of the labeling in effect before the revision will not adversely impact the safe use of the drug product."
Those changes may be made using a Changes Being Effected (CBE) supplement within 60 days (CBE-60), and FDA said its staff will track the submission of these changes using its Document Archiving Reporting and Regulatory Tracking System (DARRTS) to keep track of fulfillment of these changes.
Given the existing statutes and legal precedent, it seems likely that FDA would rescind approval for any product that does not have conformity with the RLD within 60 days, though it is unclear if the clock would reset if the RLD submitted additional changes in between the time of approval and the due date of the ANDA holder's CBE-60.
This should in theory cut down on the number of last-minute labeling changes conducted by branded pharmaceutical companies, who have used the tactic at times to delay their generic competitors.
While this can sometimes only have the effect of delaying an ANDA approval by a few weeks, a blockbuster drug by its very definition (a drug grossing more than $1 billion per year) brings in about $2.75 million per day in revenue at minimum. Each day generic competition is delayed is another day without cheaper competitors, which undercut current pricing by huge margins.
Read the MAPP:
Generic Drug Labeling Revisions Covered Under Section 505(j)(10) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)