Regulatory Signal: FDA Correction Notice — Elite Laboratories, Inc., et al.; Withdrawal of Approval of 72 Abbreviated New Drug Applications; Correction | Federal Register, March 26, 2026 | FR Doc. 2026-05913
A small correction notice buried in the Federal Register turns out to carry a large lesson about ANDA portfolio management and the organizational costs of passive regulatory monitoring.
On March 26, 2026, the FDA published FR Doc. 2026-05913 in the Federal Register — a correction to a September 2025 batch ANDA withdrawal action covering 72 abbreviated new drug applications from multiple manufacturers. The correction restored the approval of a single ANDA: number 070631 for valproic acid capsules, 250 milligrams, held by Upsher-Smith Laboratories, LLC. The reason for the correction? Upsher-Smith had timely notified FDA that it did not want the approval withdrawn — and because it acted before the effective date, the approval was never legitimately extinguished.
This event is not unusual in absolute terms. Corrections to batch ANDA withdrawal notices have been published for other companies — Hospira in 2022, TG United in 2021, Sebela Ireland in 2018 — using the same mechanism and the same procedural logic. What makes this one worth examining carefully is not the correction itself, but the regulatory infrastructure it reveals: a system where the approval of a critical anticonvulsant medication hangs on whether someone at a pharmaceutical company monitors the Federal Register and responds within a defined window.
For regulatory affairs teams managing ANDA portfolios, the mechanics and implications of this event are directly actionable.
The Original Action: What the September 2025 Withdrawal Actually Was
On September 24, 2025, the FDA published FR Doc. 2025-18453 in Volume 90, Number 183 of the Federal Register, at pages 45942 through 45944. The notice announced the withdrawal of approval of 72 ANDAs from multiple applicants. The lead-named company was Elite Laboratories, Inc.; the "et al." encompassed a larger group of applicants who had all submitted voluntary withdrawal requests to FDA.
The effective date of the withdrawal was October 23, 2025 — 29 days after publication, the standard window for these actions.
The legal authority for the action was 21 CFR 314.150, the regulation governing withdrawal of approval of new drug applications and abbreviated applications. Critically, the reason for each withdrawal was the same across all 72 ANDAs: the applicants had notified FDA in writing that their drug products were no longer being marketed, and they voluntarily requested withdrawal of the applications. This is a routine portfolio-pruning action that pharmaceutical companies undertake regularly as they exit product categories, rationalize their generics portfolio, or respond to market dynamics that make continued maintenance of dormant approvals no longer worthwhile.
Batch withdrawal notices serve an important administrative function. The FDA Orange Book — formally titled Approved Drug Products with Therapeutic Equivalence Evaluations — is the authoritative reference for approved drugs, their therapeutic equivalence ratings, and their current market status. When drug approvals are withdrawn, the Orange Book must reflect that change. Publishing grouped withdrawal notices is how FDA formally updates that record.
Why Batch Withdrawals Are Routine — and Why That Routineness Creates Risk
The irony of routine is that it breeds inattention. Because batch ANDA withdrawal notices are standard FDA housekeeping, regulatory affairs teams at pharmaceutical companies may not have formal processes for reviewing every Federal Register notice against their live ANDA portfolio. The assumption is: "We know what we requested to withdraw. We didn't request this one. Therefore, this notice doesn't affect us."
That assumption failed at some point in the timeline of ANDA 070631.
Upsher-Smith Laboratories, LLC, based at 6701 Evenstad Drive in Maple Grove, Minnesota, held ANDA 070631 for valproic acid, capsule, 250 milligrams. This ANDA was erroneously included in the September 2025 batch withdrawal table. The company did not request withdrawal of this application. Valproic acid is an active product for Upsher-Smith — their website lists valproic acid capsules, USP as a current product offering.
The fact that a correction was ultimately published confirms that Upsher-Smith's regulatory team caught the error and acted on it. But the scenario underscores a structural vulnerability in how ANDA portfolios are managed: when FDA publishes a grouped action affecting dozens of applicants simultaneously, the probability of at least one erroneous inclusion rises with the count of ANDAs in the notice.
The Correction: ANDA 070631 and the Valproic Acid Question
FR Doc. 2026-05913, published March 26, 2026, is a correction to the original September 2025 notice. It removes the entry for ANDA 070631 from the withdrawal table on page 45943 of 90 FR 45942. The operative language is precise:
Before FDA withdrew the approval of ANDA 070631, Upsher-Smith Laboratories, LLC, timely informed FDA that it did not want the approval of the ANDA withdrawn. Because Upsher-Smith Laboratories, LLC timely requested that approval of the ANDA not be withdrawn, the approval is still in effect.
This language establishes several things. First, the withdrawal had not yet taken effect when Upsher-Smith acted — the company submitted its objection before the October 23, 2025 effective date. Second, the correction is not a reinstatement of an already-withdrawn approval; it is a declaration that the withdrawal never validly applied to this ANDA in the first place. Third, the March 2026 correction notice — published roughly five months after the original action — reflects the administrative timeline for processing the objection, verifying it, and publishing the formal record correction.
Why Valproic Acid Specifically Matters
Valproic acid is not an incidental product. It is an anticonvulsant and mood stabilizer with a long clinical history, used to treat epilepsy (including complex partial seizures and absence seizures), bipolar disorder, and migraine prevention. The 250 milligram capsule formulation is the foundation dose for titration in epilepsy management. Patients on anticonvulsants are among the highest-risk populations for medication supply disruptions — abrupt changes in drug availability can precipitate seizures with serious clinical consequences.
The FDA Orange Book currently lists multiple generic manufacturers of valproic acid capsules, so the market was not dependent solely on Upsher-Smith's ANDA 070631. Nevertheless, any erroneous withdrawal of a generic ANDA for a critical neurological medication has downstream implications: pharmacists consulting the Orange Book for therapeutic equivalence data, payers relying on Orange Book status for formulary decisions, and hospital procurement teams tracking market supply all depend on the accuracy of that database. An erroneously withdrawn approval creates confusion that takes time to resolve even after the correction is published.
The Timely Objection Mechanism: How It Works and What Triggers It
The regulatory mechanism that saved ANDA 070631 deserves a careful explanation because it is not widely understood outside of pharmaceutical regulatory affairs circles — and because misunderstanding it (or being unaware of it) means losing the window entirely.
Under 21 CFR 314.150, FDA may withdraw approval of an ANDA on voluntary request from the applicant. When this happens through a batch process, FDA publishes a Federal Register notice specifying the affected ANDAs, the applicants, and the effective date of the withdrawal. The effective date is typically set approximately 30 days after publication, providing a brief but real window for administrative review.
If an ANDA holder discovers that its application has been erroneously included in a withdrawal table, the holder can timely inform FDA — in writing — that it does not want the approval withdrawn. This is the timely objection mechanism. When the objection is submitted before the effective date, FDA treats the withdrawal as inapplicable to that ANDA, and the approval remains in effect. A correction notice is subsequently published to remove the erroneous entry from the official record.
The mechanism is not a formal hearing or an administrative appeal. It is a practical safeguard against clerical errors that enables FDA to correct its record without forcing the affected party through a full adjudicatory process. The analogy in quality management terms is something like a documented nonconformance correction: the error is identified, the affected record is corrected, and the correction is documented in the official record.
What Happens If You Miss the Window
This is the question that should concentrate the attention of every regulatory affairs team managing a generic drug portfolio. If an ANDA holder does not timely inform FDA before the effective date, the withdrawal takes effect. The approval is extinguished. At that point, the company is no longer authorized to market the product under that ANDA. Restoring the approval would require a new application — and the pathway back is substantially more burdensome than the objection mechanism that was available before the effective date.
There is also an Orange Book consequence. Once a withdrawal takes effect, the product is moved from the active section to the discontinued section of the Orange Book. Downstream systems — formularies, pharmacy benefit management software, hospital purchasing databases — that pull from Orange Book data will reflect the discontinued status. Even after a correction notice is published, the administrative work of restoring the product's active standing can take time, and market confusion may persist.
For a product like valproic acid, where the clinical population depends on consistent supply, the stakes of missing the objection window are not purely administrative.
Regulatory Framework Deep-Dive: 21 CFR 314.150 and the Voluntary Withdrawal Landscape
Understanding the legal architecture around ANDA withdrawals is essential context for quality and regulatory affairs professionals.
21 CFR 314.150 is the governing regulation for withdrawal of approval of new drug applications and abbreviated applications. It covers both involuntary withdrawals — initiated by FDA based on safety, efficacy, or compliance concerns — and voluntary withdrawals, where the applicant requests that its own approval be removed. The September 2025 action and its March 2026 correction fall entirely within the voluntary withdrawal framework under 21 CFR 314.150(c).
Voluntary withdrawal requests are initiated by the applicant. The applicant notifies FDA in writing that the drug product is no longer being marketed and requests withdrawal of the approval. This is a routine portfolio decision made by pharmaceutical companies for any number of legitimate business reasons: the product is no longer commercially viable, the manufacturer has exited the therapeutic category, raw material sourcing is no longer feasible, or the regulatory cost of maintaining the approval exceeds its commercial value.
The 180-Day Notice Requirement Under Section 506I
A related but distinct regulatory obligation applies to the marketing withdrawal process itself. Under Section 506I of the Federal Food, Drug, and Cosmetic Act — added by the FDA Reauthorization Act of 2017 (FDARA) — NDA and ANDA holders must provide FDA with written notification at least 180 days prior to withdrawing an approved drug from commercial sale. This is separate from the formal withdrawal of the ANDA approval itself; it is a supply-chain transparency measure designed to give FDA, healthcare systems, and the public advance warning of potential supply disruptions for marketed products.
The 180-day notice is not a request for approval to discontinue — it is a unilateral notification obligation. FDA cannot prevent a manufacturer from discontinuing a product, but it needs early warning to assess whether the discontinuation will create a shortage, particularly for drugs with narrow therapeutic alternatives. Non-compliance with the 180-day notice requirement is itself a violation of the FD&C Act.
For generic drug manufacturers, this creates a two-step regulatory obligation when exiting a product: first, the 180-day advance notice of marketing withdrawal, and second, the separate voluntary withdrawal request for the ANDA approval itself. These are sequential steps in a properly managed product exit process.
Involuntary vs. Voluntary Withdrawal: Why the Distinction Matters
When FDA withdraws approval based on safety or efficacy concerns under 21 CFR 314.150(a) or (b), the consequences for the Orange Book are more severe — the product may be removed entirely rather than simply moved to the discontinued section. A voluntary withdrawal is treated as a commercial decision rather than a regulatory sanction, and the product entry is moved to the discontinued section with a notation that the withdrawal was not for safety or efficacy reasons.
This distinction carries real consequences for other ANDA holders. Under FDA regulations, applicants with pending or approved ANDAs that reference a listed drug may face regulatory complications if that listed drug's approval is withdrawn for safety or efficacy reasons. When a withdrawal is voluntary and for commercial reasons, other ANDAs relying on that product as a reference listed drug generally remain valid. The FDA has a standing process — including periodic Federal Register publications — for explicitly designating withdrawn products as having been withdrawn for reasons other than safety or efficacy, which preserves the regulatory standing of dependent ANDAs.
Broader Implications: Orange Book Accuracy, Generic Competition, and Supply Chain Risk
The Upsher-Smith correction is a single data point, but it illuminates a broader dynamic worth examining: the downstream effects of Orange Book data errors on the generic pharmaceutical ecosystem.
Orange Book Accuracy as a Public Health Infrastructure Issue
The Orange Book is not merely a regulatory reference — it is operational infrastructure. Pharmacists use it to verify therapeutic equivalence when making substitution decisions. Payers and pharmacy benefit managers use it for formulary design. Hospital procurement systems use it to identify approved generic sources. Health systems use it to track supply chain risk for critical medications.
When an ANDA is erroneously listed as withdrawn in the Orange Book, those downstream systems register the change. A pharmacist who pulls an Orange Book query on valproic acid 250mg capsules in October 2025 would have seen ANDA 070631 as withdrawn — even though Upsher-Smith's correction was already in process. The official correction was not published until March 2026, nearly five months after the original notice.
That five-month gap between an erroneous withdrawal entry and its correction is a window during which downstream actors may have made decisions based on inaccurate data. The impact in this specific case was likely modest — other manufacturers hold approved valproic acid ANDAs — but in a market with fewer generic competitors, a similar error on a more narrowly supplied drug could have real clinical consequences.
Generic Market Dynamics and 180-Day Exclusivity
For generic drugs where 180-day exclusivity is in play, ANDA approval status is particularly consequential. The 180-day exclusivity period — awarded to the first generic applicant to file a Paragraph IV certification challenging a brand-name patent — creates a temporary window of reduced competition that has significant commercial value. If an error in an FDA withdrawal notice affects an ANDA that is either holding or entitled to 180-day exclusivity, the downstream market implications multiply substantially.
Valproic acid is a mature generic with no active exclusivity considerations, so this dimension does not apply to the Upsher-Smith correction specifically. But the principle is important for regulatory affairs teams managing portfolios that include products in earlier stages of generic competition.
Supply Chain Risk and Pharmaceutical QMS Obligations
From a quality management systems perspective, the obligation to monitor Federal Register publications affecting your ANDA portfolio is not merely a good practice — it is an element of the broader regulatory compliance program that underlies your manufacturing authorization. An approval that you allow to lapse through inaction is no longer a valid authorization to manufacture and distribute the product. Manufacturing under a withdrawn approval is a serious regulatory violation, regardless of whether the withdrawal resulted from an FDA error that you failed to catch.
This is the inverse of the timely objection mechanism's promise: the mechanism protects you if you act, but it does not protect you if you don't.
What This Reveals About FDA's Correction Process
Before addressing what manufacturers should do, it is worth noting what this episode reveals about the regulatory system itself — and why the correction mechanism is a feature, not a defect.
The FDA publishes batch ANDA withdrawal notices covering dozens of applicants simultaneously because it is an efficient administrative mechanism. Grouping related actions reduces the Federal Register publication burden and consolidates the public record. The tradeoff is that efficiency at scale increases the probability of individual errors — a single erroneous ANDA inclusion in a 72-ANDA withdrawal table is not a systemic failure; it is a predictable feature of batch processing at volume.
What matters is that the system has a correction mechanism and that the mechanism works. The timely objection procedure, the subsequent correction notice, and the restoration of the approval to active status represent the system functioning as designed. Similar corrections have been published for Hospira (2022), TG United (2021), Sebela Ireland (2018), and others. Each correction affirms that an affected applicant monitored the Federal Register, identified the error, and acted within the required window — exactly the behavior the system expects and requires.
The critical insight is this: the regulatory system does not assume passivity on the part of regulated entities. FDA published the correction because Upsher-Smith engaged with the process actively. Had the company not monitored the original notice and responded, there would have been no correction. The system works — but only if the company participates in it.
Practical Action Items for Regulatory Affairs and Quality Management Teams
The Upsher-Smith correction is a useful case study for identifying specific operational improvements that pharmaceutical regulatory affairs and quality teams should consider. These recommendations apply to any company holding one or more ANDAs or NDAs.
1. Establish Formal Federal Register Monitoring for ANDA Portfolio
The FDA Federal Register publishes daily notices. Not every notice is relevant to your portfolio, but ANDA withdrawal notices absolutely are. Establish a formal, documented procedure for monitoring Federal Register publications, specifically filtering for notices that could affect your company's approved applications. The FDA provides email alert subscriptions through the Federal Register's notification system, and FDA's Drug Approvals and Databases page provides regular updates. Assign this monitoring task to a named regulatory affairs officer with documented accountability.
2. Maintain a Live ANDA Status Registry
Every company holding ANDAs should maintain a current registry mapping each ANDA number to its holder of record, the drug product it covers, its current regulatory status (approved, withdrawn, tentatively approved), and any pending regulatory actions. This registry is the first-line check when a Federal Register notice is identified — the responsible team member should be able to cross-reference the published withdrawal table against the internal registry within hours of publication.
3. Define an Escalation Protocol with Response Timeline
The window between publication of a batch ANDA withdrawal notice and its effective date is typically approximately 30 days. That window sounds generous until you account for publication on a Friday, holiday scheduling, or vacations. Define an escalation protocol specifying: who receives the alert, who reviews the Federal Register notice against the ANDA registry, what constitutes an actionable discrepancy, who has authority to submit a formal objection to FDA, and what the maximum response timeline is. The target response time from publication to internal review should be measured in days, not weeks.
4. Document the Review Process
From a quality management systems standpoint, regulatory monitoring activities should be documented in a manner that creates an auditable record. When your team reviews a Federal Register ANDA withdrawal notice and confirms that none of your ANDAs are affected, that review should be logged. When a discrepancy is identified and an objection is submitted to FDA, the complete chain of records — the published notice, the internal review, the objection letter, and FDA's confirmation — should be retained as regulatory records. This documentation supports both GMP compliance and risk management.
5. Incorporate ANDA Monitoring into Your Management Review Process
Under pharmaceutical GMP regulations (and by analogy under ISO 13485 for combination product manufacturers), management review is the periodic process by which senior quality and regulatory leadership assess the adequacy and effectiveness of the quality management system. ANDA portfolio monitoring — including any instances where Federal Register notices required review or action — should be a standing input to management review. This elevates the activity from ad-hoc task to systemic function.
6. Audit Your Current ANDA Portfolio Against the Orange Book
Regardless of whether you believe any of your ANDAs have been affected by recent batch withdrawal notices, conducting a periodic cross-reference of your internal ANDA registry against FDA's Orange Book active and discontinued listings is good practice. Discrepancies between your internal records and the Orange Book — in either direction — warrant investigation. This audit should be scheduled at a defined frequency, not just triggered by events.
Conclusion: A Correction That Validates the System — and the Obligation to Engage With It
FR Doc. 2026-05913 correcting the Elite Laboratories batch ANDA withdrawal will not appear in most pharmaceutical industry news summaries. It is a minor administrative notice, a routine correction of a routine batch action. The FDA publishes these corrections regularly and will continue to do so.
But the event is worth studying precisely because of its ordinariness. Every batch ANDA withdrawal notice is a test of whether affected manufacturers are actively monitoring the Federal Register. Every correction notice is evidence that at least one manufacturer passed that test. The absence of a correction notice does not prove that no errors occurred — it may simply mean that affected companies did not catch them in time.
The regulatory system that governs ANDA approvals is not passive. It publishes notices, sets effective dates, provides objection mechanisms, and publishes corrections — but it does not contact manufacturers individually when their applications are included in batch actions. The responsibility for monitoring rests with the applicant. For pharmaceutical quality and regulatory affairs teams, the Upsher-Smith valproic acid correction is a useful reminder that regulatory compliance is not just about what you file and what you manufacture. It is also about what you read, how quickly you read it, and whether your internal systems are built to act on it.
The approval of ANDA 070631 was preserved because someone at Upsher-Smith was paying attention. That is the lesson.
Citation-Ready Summary: Key Facts for Reference
On September 24, 2025, the FDA published FR Doc. 2025-18453 (90 FR 183, page 45942), announcing withdrawal of approval of 72 ANDAs from multiple applicants, effective October 23, 2025. The action was voluntary, initiated by applicant requests under 21 CFR 314.150(c).
ANDA 070631, for valproic acid capsules 250 mg, held by Upsher-Smith Laboratories, LLC, was erroneously included in the withdrawal table. Before the effective date, Upsher-Smith timely informed FDA that it did not want the approval withdrawn. Because the objection was timely, the approval remained in effect.
On March 26, 2026, the FDA published FR Doc. 2026-05913, a correction notice removing ANDA 070631 from the withdrawal table on page 45943 of the original notice. The correction affirms that the approval of ANDA 070631 is still in effect.
Primary sources: FR Doc. 2026-05913 (March 26, 2026) and FR Doc. 2025-18453 (September 24, 2025, 90 FR 45942).
About the Author
Jared Clark, JD, MBA, PMP, CMQ-OE, CPGP, CFSQA, RAC is the Principal Consultant at Certify Consulting, where he has guided 200+ medical device and pharmaceutical manufacturers through FDA submissions, ISO 13485 certification, and regulatory compliance programs — with a 100% first-time audit pass rate over 8+ years of practice. Jared specializes in QMS strategy, regulatory affairs, and FDA compliance for life sciences companies from startup to enterprise scale.
Last updated: 2026-04-09
Primary source: FDA Federal Register, FR Doc. 2026-05913, March 26, 2026. Original action: FR Doc. 2025-18453, 90 FR 183, September 24, 2025.
Jared Clark
Principal Consultant, Certify Consulting
Jared Clark is the founder of Certify Consulting, helping organizations achieve and maintain compliance with international standards and regulatory requirements.