Drug Approval Process in the USA: Step-by-Step Guide to FDA Approval

  • Admin
  • Drug Development
  • 4 July 2025

The U.S. Food and Drug Administration (FDA) sets the global gold standard for drug regulation. If a drug clears the FDA, it’s trusted worldwide — from India to Europe to Australia.

But that trust is earned, not granted. Through the Center for Drug Evaluation and Research (CDER), the FDA reviews every drug for safety, efficacy, and manufacturing quality before it ever reaches a patient.

The process is long and  also expensive, with costs exceeding large sums of money for many new therapies. More importantly, approval is just the start. Once a drug is on the market, the FDA continues surveillance to detect rare risks, issue label changes, or pull unsafe products.

In this guide, we’ll break down the full US drug registration process, from preclinical studies to post-marketing monitoring, so your team knows what to expect, where most companies fail, and how to stay ahead of the curve.

What Is the FDA Drug Approval Process?

Getting a drug approved in the US is a marathon, not a sprint. The FDA doesn’t gamble on safety. Every drug must survive a 4-stage review.

The process is managed by the Center for Drug Evaluation and Research (CDER). They decide what hits the market — and what doesn’t. Here’s an overview of the steps involved:

1. Preclinical Research & IND Application; Before human testing begins, the drug is tested in labs and animals for safety, toxicity, and pharmacology. An IND application is then submitted to the FDA.

2. Clinical Trials (Phases I–III): The drug is tested on humans in three escalating phases to assess safety, dosage, and effectiveness. Most drugs fail somewhere in this stage.

3. New Drug Application (NDA) Review: If trials succeed, the sponsor submits an NDA to the FDA. Experts review the data to determine if the drug is safe, effective, and label-ready.

4. Post-Marketing Surveillance (Phase IV): After approval, the drug is monitored in real-world use for long-term safety, new risks, and potential label updates through FDA’s MedWatch system.

You might also like: Drug Approval Process in India

Preclinical Research and IND Application

Every drug starts in a lab. Most don’t make it out. Before humans get involved, the drug goes through preclinical testing — usually on animals and in vitro systems, to assess if is it safe enough to test on people?

Researchers look at:

  • Toxicity
  • Dosage range
  • How it’s absorbed, distributed, metabolized, and excreted (ADME)
  • Short- and long-term organ damage

If the drug passes this round, the sponsor files an IND, Investigational New Drug application, with the FDA.

This is the official request to start clinical trials in humans.

What’s Inside the IND?

The IND isn’t just paperwork. It’s a full technical dossier. It must include:

  • Manufacturing details
  • Quality and stability data
  • Pharmacology and toxicology results
  • Full clinical trial protocol (who, what, how, how long)
  • Investigator qualifications
  • Plans for patient consent and safety monitoring

Here’s the catch:

The FDA does not “approve” an IND. Instead, the FDA has 30 days to place a clinical hold. If they don’t, the IND automatically goes into effect, and human trials can begin.

During those 30 days, two things happen:

  1. FDA Review – Focuses on safety, scientific rationale, and manufacturing quality.
  2. Institutional Review Board (IRB) Review – Ensures ethics, patient protection, and informed consent.

If either party raises serious concerns, trials are halted.

Clinical Trials (Phases I to III)

Once the FDA clears your IND, the drug moves into clinical trials. This is where human testing begins. Most drugs don’t survive this stage. It’s long, expensive, and highly regulated.

Here’s how it works:

Phase I: Prove It’s Safe

  • Goal: Basic safety
  • Subjects: 20 to 80 healthy volunteers
  • Duration: About 1 year

Researchers study how the drug behaves in the body — absorption, metabolism, and elimination. Side effects are recorded in detail.

At this stage, effectiveness isn’t the focus. Just safety.

Real-World Example: In 2023, a new oral diabetes drug passed Phase I by showing no serious adverse effects in 40 volunteers.

Phase II: Test If It Works

  • Goal: Early signs of efficacy
  • Subjects: 40 to 300 patients (real-world disease population)
  • Duration: 1 to 2 years

Here, the drug is tested in people with the target condition. Researchers measure outcomes, compare dosages, and track common side effects. Placebos or existing treatments are often used for comparison.

Example: A rheumatoid arthritis drug in 2022 showed 50% improvement over placebo in 220 patients. It moved to Phase III within months.

Phase III: Confirm Everything at Scale

  • Goal: Prove safety and efficacy at population scale
  • Subjects: 300 to 3,000+ patients
  • Duration: 2 to 4 years

This is the final, most expensive trial phase. It uses large, diverse patient groups to detect rare side effects and validate effectiveness across age, gender, and ethnicity. The data from Phase III forms the core of the New Drug Application (NDA).

Example: in 2024, Lykos Therapeutics’ MDMA dose couldn’t pass post the third clinical trial.

If your drug makes it through Phase III, you're one of the lucky few.

New Drug Application (NDA) Review

If your drug survives clinical trials, you’re not done — not even close. Now you ask the FDA to approve it. That request is called a New Drug Application (NDA).

What Is an NDA?

It’s your final pitch. The NDA contains everything:

  • Clinical data
  • Preclinical results
  • Side effects
  • Dosage guidelines
  • Manufacturing methods
  • Labeling information
  • Pharmacokinetics

Thousands of pages. Every sentence matters. If your submission is sloppy, expect delays, or a flat rejection. The FDA’s Center for Drug Evaluation and Research (CDER) handles it. They assign a review team: doctors, scientists, pharmacologists, statisticians, and label experts.

They don’t just look at results, they look at risk vs. reward. Is the drug effective enough for its side effects? Is the label clear? They also inspect the manufacturing site. If it fails, the drug fails.

Post-Marketing Surveillance (Phase IV)

FDA approval isn’t the finish line. It’s just a green light to start watching even closer. Clinical trials use a few thousand patients at most. The general public? Millions. Different genetics. Different conditions. Different outcomes.

That’s why rare side effects and long-term risks often appear after approval. Phase IV is about catching what Phase III missed.

Phase IV studies track:

  • Long-term safety
  • Real-world effectiveness
  • New or rare side effects
  • Off-label usage trends
  • Potential for new indications

These studies are often required by the FDA, especially for accelerated approvals. They may also support label updates or extended approvals for new patient groups.

What Is the MedWatch System?

MedWatch is the FDA’s adverse event reporting platform. Doctors, patients, and manufacturers can report problems or unexpected reactions. For example: Merck had to withdraw Vioxx, in September 2004 as it revealed that it could increase the risk of heart and stroke, despite being approved in May 1999.

Serious findings lead to:

  • Label changes
  • Boxed Warnings (the FDA’s most serious safety flag)
  • Product recalls or market withdrawal

If a risk outweighs the benefit, the FDA can act fast, and publicly. Your drug may be approved, but it’s still under review. The FDA never stops watching. Neither should you.

Why Market Entry May Still Be Delayed After FDA Approval?

FDA approval does not guarantee immediate launch. Other factors that can delay launch:

  • Manufacturing or packaging issues
  • Insurance coverage delays
  • Pricing strategy conflicts
  • Legal or patent litigation
  • Internal sales training and logistics

Some drugs receive approval but are never launched due to commercial challenges.

TL;DR – FDA Drug Approval Process in the USA

Getting a drug approved in the U.S. takes 12–15 years, costs millions, and moves through 4 key phases:

  1. Preclinical Research + IND: Test in labs and animals. Submit an Investigational New Drug (IND) application.
  2. Clinical Trials (Phases I–III): Test on humans for safety, efficacy, and dosage across 3 phases.
  3. New Drug Application (NDA): Submit full data to FDA. Approval takes 6–10 months via CDER review.
  4. Post-Marketing (Phase IV): Once launched, safety monitoring continues via MedWatch and real-world studies.

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