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

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

When you pick up a prescription at the pharmacy, there’s a 90% chance it’s a generic drug. That’s not luck-it’s the result of a carefully designed system called the Abbreviated New Drug Application (ANDA) process. This is how generic drugs get approved in the U.S., and it’s one of the biggest reasons prescription prices are so much lower than they used to be. But how does it actually work? And why does it matter if you’re paying for medicine or running a drug company?

What Is the ANDA Process, Really?

The ANDA process isn’t about inventing new drugs. It’s about copying them-safely, legally, and efficiently. Before 1984, companies had to run full clinical trials to prove a generic version was safe and effective, just like the original brand-name drug. That cost hundreds of millions and took years. It didn’t make sense. If a drug was already proven safe, why force every copycat to start from scratch?

That changed with the Hatch-Waxman Act, signed by President Reagan in September 1984. The law created the ANDA pathway under Section 505(j) of the Federal Food, Drug, and Cosmetic Act. It let generic manufacturers skip the expensive clinical trials. Instead, they just had to prove their version worked the same way as the original-called the Reference Listed Drug (RLD).

This wasn’t a loophole. It was a science-based shortcut. The FDA had already reviewed the brand drug’s safety and effectiveness. The generic company didn’t need to redo that. They just needed to show their version matched it in key ways: same active ingredient, same dose, same form (pill, injection, cream), same way it’s taken, and same effect in the body.

How the ANDA Process Works Step by Step

The ANDA process isn’t quick, but it’s predictable. Here’s how it flows:

  1. Submission: The company files an electronic application using FDA’s Electronic Submission Gateway. They include FDA-356h (the application form) and FDA-3674 (financial disclosure). The filing team checks if everything’s there. If not, they reject it within 60 days.
  2. Review: The FDA’s Office of Generic Drugs (OGD) splits the application among teams: chemistry, manufacturing, bioequivalence, labeling, and microbiology. Each team digs into their part. For example, the bioequivalence team checks if the generic drug enters the bloodstream at the same rate and level as the brand. If it doesn’t, it gets rejected.
  3. Questions and Fixes: Most applications get feedback. These are called Information Requests (IRs). A company might get 10, 15, or even 20 of them. Common issues? Poor bioequivalence data, manufacturing problems, or labeling mismatches. Companies fix these and resubmit.
  4. Approval: If everything passes, the FDA gives Final Approval. But here’s the twist: sometimes, it’s only a Tentative Approval. That means the science is solid, but the brand drug still has patent protection or exclusivity. The generic can’t launch yet. It has to wait.
The whole process takes about 30 months on average. But under GDUFA III (the latest user fee agreement), the FDA aims to review original ANDAs in 10 months. That’s the goal-not always the reality. Many companies still wait longer because of backlogs or complex products.

Why Generic Drugs Cost So Much Less

Brand-name drugs cost $2.3 billion to develop, on average. That includes 10-15 years of research, clinical trials, and regulatory hurdles. Generics? Around $1-5 million. Why? Because they’re not starting from zero.

They don’t pay for the original research. They don’t run massive Phase III trials. They don’t spend millions on marketing to convince doctors. Their job is simpler: match the original exactly.

That’s why generics make up 90% of prescriptions but only 23% of drug spending. In 2021 alone, they saved the U.S. healthcare system $373 billion. That’s not a small number. That’s enough to cover the entire Medicare Part D program for over a year.

And the savings don’t stop at the pharmacy counter. Once a generic hits the market, the brand-name drug’s price often drops by 85% within a year. That’s competition at work.

What Makes a Generic Drug “Equivalent”?

It’s not enough to say, “It has the same chemical.” The body doesn’t care about the molecule alone. It cares about how it’s delivered.

The ANDA requires proof of bioequivalence. That means the generic drug must be absorbed into the bloodstream at the same rate and to the same extent as the brand. If it’s absorbed too fast, you could get side effects. Too slow, and it won’t work.

For simple pills, this is straightforward. But for complex products-like inhalers, injectables, or topical creams-it’s much harder. These are called “complex generics.” They’re harder to copy because small changes in manufacturing affect how the drug behaves.

That’s why 35% of Complete Response Letters from the FDA in 2022 cited bioequivalence issues. One company spent $1.2 million and went through three rounds of testing just to get their topical cream approved.

The FDA now has over 2,000 product-specific guidances to help companies navigate this. Still, it’s a minefield. That’s why many generic makers use pre-ANDA meetings-where they talk to the FDA before submitting. About 78% of successful applicants do this.

Generic drug developer facing off against a corporate entity over patent documents, with a balanced scale of pills glowing equally.

Patents, Exclusivity, and the Waiting Game

Here’s the catch: even if your generic is perfect, you might not be able to sell it right away.

Brand-name companies often protect their drugs with patents. Sometimes they file multiple patents on little things-like the pill coating or the way it’s packaged. This is called a “patent thicket.” It’s legal, but it delays generics.

The Hatch-Waxman Act lets generic companies challenge these patents. They file a certification: either the patent is invalid, or they won’t infringe it. If they challenge a patent and win in court, they get 180 days of market exclusivity as a reward. That’s why some generic companies rush to be the first to file.

But if the brand has data exclusivity (usually 5 years for new drugs), the FDA can’t approve the generic until that period ends-even if the patent expires. That’s why some generics sit in “tentative approval” for years.

Who’s Playing the Game?

The generic drug market is dominated by a few big players. Teva holds about 22% of the U.S. market. Viatris (formerly Mylan) has 15%. Sandoz has 12%. Together, these three companies account for nearly half of all generic sales.

But there are thousands of smaller companies too. About 75% of ANDAs come from firms that already have five or more approved products. That’s because experience matters. One company told regulators after their 10th ANDA: “We hit GDUFA timelines 92% of the time.”

Newer companies often struggle. The average application requires 5,000-10,000 hours of work. That’s like one full-time employee working for 3-5 years. Most startups don’t have that kind of bandwidth.

What’s Changing in 2026?

The ANDA process isn’t frozen in time. The FDA is pushing hard to improve it.

- Complex generics are now 35% of pending applications. The agency is developing new testing methods, including using real-world data and AI tools. Over 78% of FDA reviewers now use AI to analyze chemistry data.

- GDUFA III (effective 2022) increased funding and set stricter deadlines. The goal: approve 90% of original ANDAs in 10 months.

- International harmonization is growing. The FDA works with the ICH to align standards with Europe, Japan, and Canada. That makes it easier for global companies to submit once and get approved in multiple countries.

- REMS restrictions (Risk Evaluation and Mitigation Strategies) are still a barrier. Some brand drugs have strict distribution rules that make it hard for generics to get samples for testing. The FDA is trying to fix this, but progress is slow.

Patients receiving generic pills at a pharmacy, each pill radiating golden light under an FDA approval stamp.

What Happens After Approval?

Approval isn’t the end. The FDA still inspects manufacturing facilities. If they find problems-like poor sanitation, bad record-keeping, or unapproved changes-the drug can be pulled from the market.

In 2022, 28% of Complete Response Letters cited facility issues. That’s why companies invest heavily in quality control. Many now use “Quality by Design” (QbD) principles, which means building quality into the process from day one, not testing it in at the end.

Once approved, generics compete fiercely. Prices drop fast. And if a new generic enters the market, the price can drop another 30-50%. That’s why pharmacies and insurers push generics-they’re cheaper, and they save money.

Why This Matters to You

If you’re a patient, the ANDA process means you can afford your meds. If you’re a caregiver, it means you don’t have to choose between medicine and rent. If you’re a taxpayer, it means Medicare and Medicaid aren’t spending billions on overpriced drugs.

If you’re a student, a pharmacist, or someone working in healthcare, understanding this system helps you explain why generics are safe. You can answer the question: “Isn’t this just a cheap copy?”

The answer is no. It’s not a copy. It’s a scientifically proven equivalent. And it’s the reason millions of Americans take their medications every day.

Common Problems and How to Avoid Them

For companies applying for an ANDA, the biggest pitfalls are:

  • Bad bioequivalence studies: Don’t use outdated protocols. Use FDA’s latest guidance.
  • Manufacturing changes: Even small changes in suppliers or equipment can trigger a rejection. Document everything.
  • Labeling mismatches: The FDA requires exact matches to the brand’s labeling-except for the company name and logo. Miss one word, and you get an IR.
  • Patent missteps: Misreading a patent can delay approval by years. Hire a regulatory attorney.
The best advice? Start early. Use pre-ANDA meetings. Build a team that includes regulatory, manufacturing, and clinical experts. And don’t assume the FDA will give you a second chance if you rush.

Is a generic drug the same as the brand-name version?

Yes, in every way that matters. Generic drugs contain the same active ingredient, work the same way in the body, and meet the same quality standards as brand-name drugs. The only differences are in inactive ingredients (like fillers or dyes) and packaging. The FDA requires proof of bioequivalence before approval, meaning the generic must deliver the same amount of medicine into the bloodstream at the same rate as the brand.

Why do some generic drugs look different from the brand?

By law, generic drugs can’t look exactly like the brand-name version. That’s because trademarks protect the appearance of brand drugs. So generics may have different colors, shapes, or markings. But the active ingredient, dose, and effect are identical. If you’re concerned, ask your pharmacist to confirm the generic is equivalent.

Are generic drugs tested by the FDA?

Yes. Every generic drug must go through the FDA’s ANDA review process, which includes strict checks on chemistry, manufacturing, bioequivalence, and labeling. The FDA also inspects the manufacturing facilities where generics are made-often more frequently than brand-name plants. There’s no difference in the standard of safety or quality.

How long does it take to get a generic drug approved?

On average, it takes about 30 months from submission to approval. But under the FDA’s current goals (GDUFA III), original ANDAs should be reviewed in 10 months. Delays often happen because of incomplete applications, complex products, or patent issues. Some generics-especially those for drugs in short supply-can be fast-tracked.

Can a generic drug be pulled from the market after approval?

Yes. If the FDA finds problems with manufacturing, quality control, or safety after approval, they can issue a recall or suspend the approval. This has happened with several generic drugs over the years, usually due to contamination or failure to meet cGMP standards. The FDA continues to inspect facilities even after approval to ensure ongoing compliance.

What’s Next for Generic Drugs?

The future of the ANDA process lies in complexity. As more drugs become biologics, complex injectables, or inhaled medications, the FDA will need better tools to evaluate them. Artificial intelligence, machine learning, and real-world evidence are becoming part of the review process.

But the goal stays the same: get safe, effective, affordable drugs to patients faster. The ANDA process isn’t perfect. It’s slow. It’s complicated. But it works. And for millions of Americans, it’s the reason they can afford to stay healthy.

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