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How should you document a listed drug’s withdrawal from sale?
Identify the exact NDA/ANDA product and strength, all relevant marketed NDCs, the holder’s distribution-stop date and supported reasons. Prepare the applicable marketing-status notification and retain its evidence. Keep that notice separate from withdrawal of approval, FDA’s determination of safety or effectiveness reasons, and any independently applicable shortage notification.
Before you begin
Listed human-drug products and the reasons-for-withdrawal framework in 21 CFR 314.161–162. Separate marketing-status and shortage notifications may also apply.
What you will prepare: A product-specific factual record and correctly routed regulatory request or notification.
Identify the event without overstating its legal effect
A decision to stop selling a product is not automatically withdrawal of FDA approval. Identify the NDA/ANDA, exact product and strength, actual marketing status, discontinuation date and supported reasons. Do not label a discontinued product “unsafe” from its Orange Book status alone.
Section 314.161 addresses FDA’s determination of whether a listed drug was voluntarily withdrawn from sale for safety or effectiveness reasons. Such a determination matters to applications relying on that listed drug. Section 314.162 separately addresses removal from the list. An applicant’s explanation is evidence for the agency; it is not the agency’s determination.
Prepare the separate section 506I marketing-status notice
For an approved NDA/ANDA product being withdrawn from sale, FDA’s final guidance describes the statutory notice 180 days before withdrawal, or, when that is not practicable, as soon as practicable and no later than withdrawal. Record the actual decision and distribution dates rather than delaying work until the product disappears from every pharmacy. The guidance distinguishes routine temporary supply interruptions from withdrawal, subject to its safety/effectiveness qualification.
Include the listed NDCs, established and proprietary names as applicable, NDA/ANDA number, strength, expected date no longer available for sale and reason. If the holder markets that strength under multiple NDCs, the guidance says to notify withdrawal when all relevant NDCs are discontinued, not when some remain marketed. Add last manufacturing, distribution and lot-expiration information if known. This notice is different from requesting withdrawal of approval and does not replace a separately applicable shortage report.
Build the factual discontinuation record
Recommended record: approved presentation and application identifiers; last/current marketing facts; discontinuation decision and evidence; safety/efficacy information relevant to the reason; related products still marketed; current approval status; applicable notices and owners. Reconcile the narrative with pharmacovigilance, quality, supply and legal records before saying a reason is purely commercial.
If requesting FDA action or responding to its inquiry, state the precise action and supply the evidence relevant to the withdrawal reason. A formal petition has its own procedural requirements; a Module 1 placement is not a substitute for them. Have the regulatory owner separately assess current statutory marketing-status and drug-shortage notification obligations rather than assuming this letter satisfies all notices.
Worked check: an ANDA team relies on a discontinued product
Fictional exercise: a reference product is no longer sold, and the ANDA team assumes it can neither be referenced nor supplied by any generic. Obtain FDA’s actual withdrawal-reason determination and current listing before drawing that conclusion. The business event alone does not answer the regulatory question.
Change the fact pattern to withdrawal of approval already ordered by FDA: the source record and downstream consequences change. If only a wholesaler’s stock status is known, it is insufficient to establish either marketing discontinuation or regulatory withdrawal.
Reconcile the product, strength and NDCs before choosing the notice
Start from the application holder’s records, not a search result saying “out of stock.” For each product and strength, map the relevant NDCs and distribution facts. FDA’s August 2020 guidance describes when the holder’s cessation of distribution constitutes withdrawal from sale; remaining downstream stock does not by itself postpone that event.
| Working field | Evidence to use | Question for the owner |
|---|---|---|
| Approved product | NDA/ANDA, names, dosage form and strength | Are we tracking the same product across regulatory and supply systems? |
| NDC coverage | Relevant NDCs and whether each remains marketed | Is a pack being discontinued while another NDC for that strength continues? |
| Distribution event | Actual or planned date the holder ceases distribution | Is this a routine temporary interruption or a discontinuation decision? |
| Reason | Commercial decision reconciled with quality and safety information | Does the proposed explanation omit a material concern? |
| Notifications | Applicable notice, basis, timing, owner and delivery evidence | Are marketing status, shortage duties and approval withdrawal being conflated? |
Pack-size exercise: the holder stops one pack-size NDC but continues another NDC for the same strength. Under the guidance’s approach, that fact alone does not support notifying FDA that the product/strength has been withdrawn from sale. If all relevant NDCs will cease marketing, reconcile them in the notification. Also consider the guidance’s branded-product/authorized-generic distinction: stopping the brand alone is not the same event when the authorized generic remains marketed.
Document uncertainty about the reason rather than defaulting to “commercial.” The supply team can establish distribution facts; safety, quality and regulatory colleagues must reconcile evidence relevant to the stated reason. An applicant’s explanation is not a substitute for FDA’s withdrawal-reason determination under §314.161.
For an ANDA relying on a discontinued listed drug, obtain the current listing and any agency determination, then assess the applicable procedure. Section 314.161 requires the withdrawal-reason determination before approval of a referencing ANDA; discontinuation alone neither settles that determination nor establishes that approval is impossible. Use the status map and approval-withdrawal guide when the request involves more than marketing status.
Your preparation checklist
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Frequently asked questions
Does one discontinued NDC mean the whole drug product is withdrawn from sale?
Not necessarily. FDA’s guidance distinguishes discontinuing some NDCs from ceasing marketing under all relevant NDCs for a particular strength. Reconcile the holder’s product and NDC records before sending a product-withdrawal notification. A packaging change alone should not be described as cessation of all marketing for that strength.
Is a temporary supply interruption always a withdrawal from sale?
No. The guidance distinguishes routine temporary interruptions from withdrawal, with a qualification for interruptions triggered by safety or effectiveness concerns. Establish the actual distribution decision and reason. Calling an interruption temporary, or planning a future return to market, does not by itself resolve the applicable classification.
Does the Orange Book discontinued section prove the drug was unsafe?
No. Discontinued marketing can have other reasons, and the listing alone is not a safety finding. Obtain FDA’s actual determination where relevant under §314.161 and distinguish it from the holder’s notification. Do not infer either unsafe status or a completed favorable determination solely from a discontinued listing.
Does a marketing-status notification also withdraw the NDA or ANDA approval?
No. FDA’s guidance distinguishes the marketing-status letter from a separate written request under §314.150(c) when voluntary withdrawal of approval is sought. Establish which action the applicant intends. Retain each applicable notice and agency disposition separately rather than marking approval withdrawn when only sales have stopped.
Sources and revisions
Requirements, source recommendations and editorial preparation advice have different roles. Review the scope and revision of the source you use.
Regulation
21 CFR Part 314: drug marketing applications ↗Current part reopened September 22, 2026; §§314.50, 314.53, 314.65, 314.72, 314.94, 314.99, 314.108 and 314.150–162 inspected. Not a general BLA rule.
Guidance
Marketing Status Notifications Under Section 506I ↗Final August 2020; §§II and III.A. Exact PDF reopened September 22, 2026; statutory timing and content distinguished from recommendations.
Technical specification · placement only
FDA eCTD v4.0 comprehensive hierarchy ↗Version 2.2, February 2025. Section 1.5.6. A heading identifies placement, not mandatory applicability.