The holidays are fast approaching and many of us are in a joyful spirit, more prone to giving and charity in alignment with the season. That said, considering the effort that goes into sponsors’ pursuit of ANDA approvals where the sponsor or sponsors may be eligible for 180-day exclusivity, I doubt that anyone in the generic industry is in a giving or charitable spirit in relation to their exclusivity. To that end, I hope this blog serves as a public service announcement of both the FDA’s interpretation of one of its regulations and the impact that its interpretation has on cohorts of first applicants that are eligible for 180-day exclusivity. The regulation in question is 21 CFR 314.107(c)(2), which reads:
A first applicant must submit correspondence to its ANDA notifying FDA within 30 days of the date of its first commercial marketing of its drug product or the reference listed drug. If an applicant does not notify FDA, as required in this paragraph (c)(2), of this date, the date of first commercial marketing will be deemed to be the date of the drug product’s approval.
At first blush, nothing seems too onerous or malevolent about the regulation as it informs applicants that if they qualify as a “first applicant” they must notify the FDA within 30 days of launch and there are consequences when the information isn’t submitted within the 30-day timeframe. There are very good policy reasons why the FDA wants this information as soon as possible, most important of which is the prioritization of subsequent applicants subject to 180-day exclusivity where the approvals of those subsequent applicants are blocked based solely on the 180-day exclusivity period. The FDA wants to ensure that it can approve as many subsequent applicants as possible once those sponsors have met all of the FDA’s requirements for approval and the exclusivity has elapsed. What this regulation doesn’t state is how the FDA interprets the “penalty provision” when there are a cohort of first applicants that share eligibility for 180-day exclusivity. For purposes of clarity, the “penalty provision” is the portion of the regulation that reads, “the date of first commercial marketing will be deemed to be the date of the drug product’s approval.”
When administering this regulation, the FDA applies timely notification within the 30-day requirement to ALL first applicants that are eligible for 180-day exclusivity. Practically speaking, what this means is that every first applicant is required to notify the FDA within 30 days of beginning commercial marketing of the product that was approved under their ANDA or an authorized generic (marketing of either product is a trigger of 180-day exclusivity). If there is a single first applicant that does not notify the FDA in a timely manner and the FDA becomes aware of this, the FDA will apply the “penalty provision” of 21 CFR 314.107(c)(2) and consider the date of approval of that application to be the date of first commercial marketing. When the FDA applies the “penalty provision,” it will result in any 180-day exclusivity period completely running out if the first applicant’s approval date was more than 180 days in the past. Fortunately, the FDA’s application of the “penalty provision” has been quite rare, with less than a handful of instances where the FDA has applied it. That said, if you are a first applicant that retains eligibility for 180-day exclusivity and you share this 180-day exclusivity with other first applicants, through no fault of your own the 180-day exclusivity may be undermined by other filed applicants.
Two thoughts on this before I provide details on the most recent application of the “penalty provision” of 314.107(c)(2). For industry, this is a relatively easy problem to avoid; each first applicant merely needs to develop the habit of providing notice of first commercial marketing within 30 days every time that they are required to provide this notice. The FDA should also review whether its interpretation and application of the “penalty provision” is the interpretation most aligned with its policy goals. To that end, first applicants could unilaterally stop providing notice of commercial launch in a timely manner, which would make it quite difficult for the FDA to obtain the information it needs to prioritize subsequent applicants as early as possible, ultimately resulting in later approvals for the subsequent applicants.
Case in point, at least as far back as the August 19, 2024 update to the FDA’s Paragraph IV List, the listing for the drug products Ivabradine Tablets, 5 mg and 7.5 mg, displayed a first commercial marketing date of July 18, 2024, which corresponds to an expiry of 180-day exclusivity on January 11, 2025.
August 19, 2024 Paragraph IV Listing Information for Ivabradine Tablets
With the November 8th update, the listing for Ivabradine Tablets, 5 mg and 7.5 mg, changed and now displays a first commercial marketing date of October 5, 2022 (see below), which corresponds to the approval date of ANDA 213366. Because of this change, the FDA was able to approve ANDA 215238 on November 8, 2024, representing a net loss of 64 days of 180-day exclusivity.
November 8, 2024 Paragraph IV Listing Information for Ivabradine Tablets
This case in point demonstrates the need for applicants to carefully follow the regulations associated with properly providing notification to the FDA of first commercial marketing of products that are eligible for 180-day market exclusivity.
