What It Takes to Withdraw an Approved Drug

Answer first: withdrawal is an order, and it follows a written list

The provision is 21 U.S.C. 355(e). It begins with a mandatory verb and a procedural condition: the Secretary "shall, after due notice and opportunity for hearing to the applicant, withdraw approval of an application with respect to any drug under this section" on any of five findings.

The five are: that clinical or other experience, tests or other scientific data "show that such drug is unsafe for use under the conditions of use upon the basis of which the application was approved"; that new evidence of clinical experience not in the application, or tests by new methods, evaluated with the evidence available at approval, "shows that such drug is not shown to be safe" under those conditions; that on the basis of new information, evaluated with the evidence available at approval, "there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have" under the labeled conditions of use; that required patent information was not filed within thirty days of written notice; or "that the application contains any untrue statement of a material fact."

Notice how two of those are asymmetric with approval. Ground one requires a showing that the drug is unsafe. Ground two requires only that it is not shown to be safe. They are different tests, and the statute lists them separately.

The section closes with a general requirement that applies to all of it: "Any order under this subsection shall state the findings upon which it is based." A withdrawal is therefore a reasoned document, not an announcement.

The same-day power, and the sentence that limits it

Inside the same subsection is a proviso for emergencies. If the Secretary "finds that there is an imminent hazard to the public health, he may suspend the approval of such application immediately, and give the applicant prompt notice of his action and afford the applicant the opportunity for an expedited hearing under this subsection."

Then comes the limit, and it is unusual enough to quote exactly: "but the authority conferred by this proviso to suspend the approval of an application shall not be delegated."

That single clause is the reason this power is rare in practice. Every other function in the section can be exercised by the agency in the ordinary way; this one is reserved to the Secretary personally. The statute pairs the fastest available action with the highest possible level of sign-off.

The regulation mirrors the sequence: where the Secretary has suspended an approval on a finding of imminent hazard, "FDA will promptly afford the applicant an expedited hearing following summary suspension." Suspension first, hearing quickly after — the reverse of the ordinary order.

A second, discretionary list about conduct rather than the drug

The same subsection contains a second sentence with a different verb. The Secretary "may also, after due notice and opportunity for hearing," withdraw approval on three further findings, and these are about the applicant rather than the molecule.

The first is records: that the applicant "has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain such records or to make required reports," or has refused to permit access to, copying of, or verification of those records.

The second is manufacturing: that on the basis of new information, evaluated with the evidence available at approval, "the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to assure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice."

The third is labeling: that on the same basis, "the labeling of such drug, based on a fair evaluation of all material facts, is false or misleading in any particular and was not corrected within a reasonable time after receipt of written notice."

Each of the last two has a cure period built in. The ground is not simply that a problem existed, but that it was not fixed within a reasonable time after written notice specifying it.

What the regulation adds, including two ways out that are not findings

Section 314.150 restates the statutory grounds and adds several of its own, drawn from the conditions of a modern application. Among them: failure to submit required bioavailability or bioequivalence data; omission from the application of a report of any investigation sponsored by the applicant, or of other pertinent information it received; a nonclinical laboratory study essential to showing safety that "was not conducted in compliance with the good laboratory practice regulations"; a clinical investigation "not conducted in compliance with" the institutional review board or informed consent regulations "such that the rights or safety of human subjects were not adequately protected"; and a refusal to permit inspection of facilities or records relevant to a bioavailability or bioequivalence study, or to submit reserve samples when requested.

For generic applications there is one more: that the labeling of the product "is no longer consistent with that for the listed drug," apart from differences approved in the application or arising from a later patent or exclusivity on the listed drug that do not make the product less safe or effective for the remaining, unprotected uses.

Two further paragraphs describe endings that are not adverse findings at all. Under paragraph (c), FDA "will withdraw approval of an application or abbreviated application if the applicant requests its withdrawal because the drug subject to the application... is no longer being marketed," provided none of the adverse conditions applies. A written request of that kind is treated as a waiver of the hearing, and the withdrawal "is without prejudice to refiling."

Under paragraph (d), FDA may tell an applicant it believes a potential problem is "sufficiently serious that the drug should be removed from the market" and ask the applicant to waive the hearing and remove the product voluntarily. If the applicant agrees, the agency does not make a finding under paragraph (b), and instead publishes a Federal Register notice containing "a brief summary of the agency's and the applicant's views of the reasons for withdrawal."

That is why some withdrawal notices read as two accounts side by side. The format is written into the regulation.

How to read a withdrawal notice without over- or under-reading it

The single most useful distinction is between a withdrawal that follows a finding and one that follows a request. An approval withdrawn because a product is no longer marketed carries no safety conclusion, is expressly without prejudice to refiling, and often reflects nothing more than a company retiring a listing. An approval withdrawn on a finding under the statutory grounds is a different document, and the statute requires it to state the findings on which it is based.

The voluntary-removal route in paragraph (d) sits between the two, and the regulation's own language is the tell: the agency does not make a finding, and the published notice summarizes both sides' views of the reasons.

Two more points are worth holding onto. A withdrawal of approval is not the same as a recall — a recall concerns product already distributed and is governed by separate rules. And withdrawal is reviewable: an applicant may appeal an order refusing or withdrawing approval to a United States court of appeals, and the statute also provides that whenever the facts so require, the Secretary "shall revoke any previous order... refusing, withdrawing, or suspending approval" and approve the application or reinstate the approval.

So the categories are: suspended on an imminent-hazard finding, withdrawn on stated findings, withdrawn at the applicant's request, or removed voluntarily with a two-sided notice. A reader who identifies which one a document belongs to has extracted almost all of what it means.