How a generic drug gets approved

In the federal fiscal year that ended Sept. 30, 2025, FDA approved 689 Abbreviated New Drug Applications and granted tentative approval to 250 more, according to the agency's GDUFA performance report to Congress¹. Among the first generics it listed were versions of rivaroxaban, liraglutide, iron sucrose and siponimod.

Every one of those products passed through the same gate, the ANDA, reviewed by the Office of Generic Drugs inside FDA's Center for Drug Evaluation and Research. About 9 out of 10 prescriptions filled in the United States are for generics, FDA says², so the speed and rigor of this review shape what most patients take.

The application is called abbreviated because the applicant generally does not repeat the animal and human studies that proved the original drug safe and effective. It relies on FDA's earlier finding for the brand and proves that its own version matches, under a pathway created by the Hatch-Waxman Act in 1984.

Every generic starts from a reference listed drug

An ANDA is always tied to one approved product, which FDA's regulatory definitions³ call the reference listed drug, "the listed drug identified by FDA as the drug product upon which an applicant relies." It is usually the original brand. FDA identifies RLDs in the Orange Book⁴, explained in our Orange Book guide.

A second defined term, the reference standard, is the exact product the applicant must test against in its bioequivalence study. Usually the two are the same product. They can differ, for example when the original brand is no longer sold.

A generic must match the RLD in active ingredient, strength, dosage form and route. A generic that departs from the RLD on one of those points first needs FDA's permission through a suitability petition⁵, which the regulation limits to a short list of allowed changes.

What goes into the application

Required contents are set by 21 CFR 314.94⁶ and described on FDA's ANDA page⁷.

• Sameness data. Evidence that the active ingredient, strength, dosage form and route match the RLD.
• Bioequivalence. Usually a pharmacokinetic study in healthy volunteers showing the generic delivers the active ingredient at the same rate and to the same extent as the reference (see the 80-125 rule). Many inhalers, creams and other complex products need other kinds of evidence.
• Chemistry, manufacturing and controls. How the active ingredient and finished product are made, tested and kept stable, and the specifications each batch must meet.
• Facilities. Every site that makes the active ingredient, makes or packages the finished product, or tests it. Each must comply with current good manufacturing practice.
• Labeling. Generally the same as the RLD's, with limited permitted differences, such as the manufacturer's name or an indication left out because a patent or exclusivity still protects it.
• Patent certifications. A statement about each patent listed for the RLD. These decide whether approval can take effect at once or must wait, and a challenge to a patent is a Paragraph IV certification.

The review, step by step

1. Before submission. Applicants read FDA's product-specific guidance⁸ for the drug, which sets out the bioequivalence studies FDA expects. For complex products they can request pre-ANDA meetings. For a priority submission, the applicant can file a Pre-Submission Facility Correspondence (PFC) at least 60 days ahead, listing its facilities so FDA can plan inspections early.
2. Receipt. FDA checks whether the application is complete enough to review. Under 21 CFR 314.101⁹, it may decline to consider an ANDA received if it is deficient, and the applicant can correct the gaps and resubmit.
3. Scientific assessment. Separate teams assess bioequivalence, product quality, labeling and, for sterile products, microbiology. Patent and exclusivity questions go to their own specialists.
4. Facility evaluation. FDA decides whether each site needs a pre-approval inspection or can be judged on its compliance history.
5. Action. FDA issues an approval, a tentative approval, or a complete response letter listing deficiencies. The applicant answers a complete response letter with an amendment, which gets its own goal date.

Review goal dates under GDUFA III

Since 2012, generic manufacturers have paid user fees under the Generic Drug User Fee Amendments, and FDA in return commits to review deadlines (our GDUFA explainer covers the fees). The current agreement, GDUFA III, covers fiscal years 2023 through 2027. For each category in its commitment letter¹⁰, FDA's target is to act on 90 percent of submissions by the goal date.

A goal date is a deadline for FDA to act. It is no promise of approval. If the first action is a complete response letter, a new clock starts when the applicant amends. If a listed facility is not ready for inspection when the ANDA arrives, the commitment letter sets a 15-month goal and FDA holds off on substantive assessment until the applicant certifies the site is ready.

Why some approvals are only tentative

An application can meet every scientific and manufacturing standard and still be blocked by a patent or exclusivity period protecting the brand. FDA then issues a tentative approval. Its approval regulation¹¹ is blunt about the status: "A drug product that is granted tentative approval is not an approved drug." The product cannot be marketed. It moves to final approval once blocking patents expire or are resolved in court and any exclusivities run out, a sequence FDA's Drugs@FDA glossary¹² also describes. The first applicant to challenge a patent may hold 180-day exclusivity, which can keep later approvals tentative.

Recent output, by fiscal and calendar year

FY 2024 figures come from FDA's FY 2024 performance report¹³, which listed first generics of pazopanib, teriparatide and liposomal bupivacaine injectable suspension.

GxRadar keeps a separate count from openFDA's Drugs@FDA records¹⁴, limited to original ANDA approvals by calendar year. It shows 743 in 2020, 624 in 2021, 733 in 2022, 754 in 2023, 712 in 2024, 648 in 2025 and 575 in 2026 through Oct. 27. The numbers differ from FDA's reports because the periods differ and FDA's totals are compiled on its own basis. Our approvals page charts the series back to 1984.

Oversight after approval

Once approved, the generic appears in the Orange Book with a therapeutic equivalence code. A code beginning with A, most often AB, tells pharmacists FDA considers the product substitutable for its reference, as the Orange Book preface¹⁵ explains; state substitution laws build on those codes, and our guide to therapeutic equivalence codes decodes them.

Approved manufacturers must keep meeting manufacturing standards, report adverse events, and file supplements before significant changes to the formula, process or site. FDA can inspect at any time, and a failed inspection can lead to a Form 483 or warning letter. Questions about receiving one generic in place of a brand, or one generic in place of another, are best taken to a pharmacist or prescriber.