FDA’s Abbreviated New Drug Application Process Explained: How Generic Drugs Get Approved

When you pick up a prescription at the pharmacy and see a generic version of your brand-name drug, you’re seeing the result of a highly structured, science-backed process called the Abbreviated New Drug Application (ANDA). It’s not a shortcut-it’s a precise, regulated pathway that lets safe, effective generic drugs reach patients at a fraction of the cost. In 2023, nearly 90% of all prescriptions filled in the U.S. were for generics, saving the healthcare system $373 billion that year. But how does the FDA make sure these cheaper drugs work just like the expensive ones? The answer lies in the ANDA process.

What Is the ANDA Process?

The ANDA is a regulatory submission to the U.S. Food and Drug Administration (FDA) that allows companies to market a generic version of a brand-name drug without repeating all the expensive clinical trials. Instead of proving the drug is safe and effective from scratch, generic manufacturers must prove their product is therapeutically equivalent to an already approved drug, called the Reference Listed Drug (RLD). This system was created by the Hatch-Waxman Act of 1984, a landmark law designed to balance innovation with access. It gave brand-name companies some patent protection while opening the door for competition once those patents expired.

The ANDA pathway is governed by Section 505(j) of the Federal Food, Drug, and Cosmetic Act. It’s not just about copying a pill. The generic version must match the RLD in every key way: same active ingredient, same strength, same dosage form (tablet, injection, capsule), same route of administration (oral, topical, etc.), and same conditions of use. Even the labeling must be nearly identical, with only minor exceptions for differences in manufacturer details or patent statements.

How the ANDA Process Works Step by Step

The ANDA process doesn’t happen overnight. It’s a multi-phase review that can take years, even for experienced companies. Here’s how it breaks down:

1. Submission: The applicant files an electronic ANDA through the FDA’s Electronic Submission Gateway. Required forms include FDA-356h (the application itself) and FDA-3674 (disclosing financial interests). The filing division checks for completeness within 60 days. If anything’s missing, the application is refused.
2. Discipline Reviews: Once accepted, the application is split among specialized FDA teams: chemistry, manufacturing, microbiology, labeling, and bioequivalence. Each team digs into their area. Chemistry checks the drug’s composition. Manufacturing reviews the facility and production methods under current Good Manufacturing Practices (cGMP). Bioequivalence is the heart of the process-did the generic drug get into the bloodstream at the same rate and amount as the brand? If not, it’s not approved.
3. Information Requests and Responses: Most applications get flagged with Information Requests (IRs). These are requests for more data, clarification, or corrections. On average, applicants receive 10-15 IRs per submission. Responding thoroughly is critical. A single unresolved issue can delay approval by months.
4. Final Decision: If all teams agree and the manufacturing site passes inspection, the FDA issues Final Approval. But sometimes, even if the science is solid, approval is delayed. That’s called Tentative Approval. It means the FDA is ready to approve-but a patent or exclusivity period on the brand drug is still active. The generic can’t launch until that protection expires.

The FDA’s goal under GDUFA III (Generic Drug User Fee Amendments, effective 2022) is to approve 90% of original ANDAs within 10 months. In 2022, they hit a 91% first-cycle approval rate. But that’s only for applications that get it right the first time. The average time from submission to approval is about 30 months due to back-and-forth reviews and inspection delays.

Why Bioequivalence Is the Make-or-Break Factor

The most common reason ANDAs get rejected? Inadequate bioequivalence data. In 2022, 35% of Complete Response Letters cited bioequivalence issues. That means the generic didn’t prove it behaves the same way in the body as the brand-name drug.

Bioequivalence is usually tested in healthy volunteers using blood samples. The generic must deliver the same amount of active ingredient into the bloodstream at the same rate as the RLD. The acceptable range is strict: the generic’s absorption must fall within 80% to 125% of the brand’s. For simple oral tablets, this is straightforward. But for complex products-like inhalers, topical creams, or injectables-it’s much harder. These require specialized studies, sometimes with patients instead of healthy volunteers. One company spent $1.2 million and three tries just to prove bioequivalence for a topical cream.

The FDA has published over 2,000 product-specific guidances to help applicants navigate these challenges. For example, there are separate guidelines for nasal sprays, transdermal patches, and complex injectables. Companies that use these guidances from the start have a much higher success rate.

ANDA vs. NDA: Why Generics Cost So Much Less

The difference between an ANDA and a New Drug Application (NDA) is massive. An NDA for a brand-new drug requires full clinical trials-Phase I, II, and III-covering safety, dosing, and effectiveness in thousands of patients. The cost? Around $2.3 billion, according to Tufts Center for the Study of Drug Development.

An ANDA? Typically $1 million to $5 million. That’s because it leans on the FDA’s prior approval of the brand drug. No need to retest safety. No need to reprove efficacy. Just prove you can make the same medicine, the same way, and it behaves the same in the body.

That’s why generic drugs cost, on average, only 15% of the brand-name price within a year of launch. The savings aren’t just theoretical-they’re in your wallet. A 30-day supply of brand-name Lipitor might cost $300. The generic version? $10. That’s the power of the ANDA process.

Who’s Behind the ANDA Submissions?

The generic drug market is dominated by a few big players. Teva Pharmaceuticals holds about 22% of the U.S. market. Viatris (formerly Mylan) and Sandoz follow with 15% and 12% respectively. But over 75% of ANDA submissions come from companies that have already approved at least five generic products. Experience matters.

Smaller companies often struggle with the complexity. One survey found that 78% of applicants face unexpected Information Requests. Another 63% report delays due to facility inspections. The FDA inspects every manufacturing site listed in the ANDA, whether it’s in the U.S., India, or China. If the site fails inspection, approval is blocked-even if the science is perfect.

Leading companies now use Quality by Design (QbD) principles to build robust manufacturing processes from the start. This reduces variability and cuts down on IRs. They also hold pre-ANDA meetings with the FDA. About 78% of successful applicants do this. It’s not required, but it’s a game-changer.

Challenges and the Future of Generic Approval

Despite its success, the ANDA process isn’t flawless. Patent thickets-where brand companies file multiple overlapping patents to delay generics-remain a major barrier. Some drugs have over 100 patents, making it hard for generics to enter even after the original patent expires.

Another growing issue: complex generics. These include drugs that are hard to replicate, like inhaled corticosteroids or long-acting injectables. In 2022, 35% of pending ANDAs were for complex products. The FDA launched its Complex Generic Drug Products Initiative in 2018 to tackle this. Today, they’re using AI tools to speed up chemistry reviews-78% of reviewers now use AI-assisted tools to analyze data faster and more accurately.

The future of ANDAs will likely involve more real-world evidence, harmonized global standards through the International Council for Harmonisation (ICH), and better tools to assess complex products. But the core principle remains unchanged: if a generic drug is proven equivalent, it deserves a place on the shelf.

What This Means for Patients

You don’t need to be a scientist to benefit from the ANDA process. When your doctor prescribes a generic, you’re getting a drug that’s been reviewed by the same agency that approved the brand-name version. The FDA holds generics to the same standards. They’re not second-rate. They’re rigorously tested alternatives.

For people managing chronic conditions-diabetes, high blood pressure, depression-switching to a generic can mean the difference between sticking with treatment and skipping doses because of cost. The ANDA process doesn’t just lower prices. It saves lives.

And while the system isn’t perfect-delays happen, inspections take time, and complex drugs are still tough to copy-it’s working. The U.S. generic drug market is projected to grow from $127.6 billion in 2022 to $189.2 billion by 2027. More competition. Lower prices. More access. That’s the real goal of the ANDA process.

Final Thoughts

The ANDA process is one of the most successful public health policies in modern medicine. It’s not flashy. It doesn’t make headlines. But it’s the quiet engine behind the billions in savings, the millions of prescriptions filled, and the lives improved because people can afford their meds. It’s science, regulation, and competition working together-and it’s working well.