Warning Letters: FDA Responses to Manufacturing Violations in Pharmaceutical Production

When the FDA finds serious problems in a drug factory, they don’t just give a nod and a smile. They send a warning letter-a formal, public notice that says: you’re breaking the rules, and we’re watching. These aren’t gentle reminders. They’re legal notices with real consequences: delayed product launches, millions in lost revenue, and even bans on selling your drugs in the U.S.

Every year, the FDA issues hundreds of these letters to pharmaceutical companies around the world. In 2023 alone, there were 327 warning letters sent to manufacturers-up from 289 the year before. That’s a 12.7% increase. And it’s not random. These letters target specific, repeat violations of Current Good Manufacturing Practices (CGMP), which are the rules that ensure drugs are consistently made safe, pure, and effective.

What Exactly Is in an FDA Warning Letter?

These letters aren’t vague. They’re detailed, technical, and exact. Each one points to specific violations using the exact language from the Code of Federal Regulations (CFR). Most commonly, they cite 21 CFR Parts 210 and 211-the rules that govern how drugs are made, tested, and controlled.

Take the July 2, 2025 letter to Daewoo Pharmaceutical Co., Ltd. The FDA found workers with exposed skin-like foreheads-inside an ISO 5 cleanroom, where sterile drugs are filled. That’s a direct breach of aseptic processing rules. Another example: non-sterile tape used on a filling line. Tape that hasn’t been sterilized can introduce bacteria into a vial of medicine. One small mistake like that can lead to a patient getting infected.

Each letter has three parts:

1. Violation details: Exactly what was seen, when, and where. Photos, logs, and inspection notes are referenced.
2. Regulatory citations: The specific CFR sections broken. No guessing allowed.
3. Required actions: What the company must do next. This isn’t optional. It’s a deadline.

For example, Oasis Medical, Inc. was told to examine every single batch of product from January 2023 onward for defects. They also had to conduct full investigations with corrective and preventive actions (CAPA)-not just fix the problem, but prove they won’t let it happen again.

Why Warning Letters Are Different from Other FDA Actions

The FDA doesn’t jump straight to shutting down a plant. They have a step-by-step enforcement ladder.

First, inspectors give a Form 483 during an inspection. It’s a list of observations-things they saw that don’t meet standards. About 62% of inspections result in a Form 483. But a warning letter? That’s the next level. Only about 18-22% of inspections with violations turn into warning letters. Why? Because the violations have to be serious, systemic, or repeated.

Warning letters are the FDA’s way of saying: We’ve seen this before, and you didn’t fix it. A 2023 analysis found that 85% of warning letters included violations that had been cited in past communications. That’s not a one-off mistake. That’s a culture problem.

Compare that to a Form 483. It’s a heads-up. A warning letter is a legal notice. It’s public. It’s on the FDA’s website forever. Investors, customers, and regulators all see it. That’s why companies panic when they get one.

Most Common Violations: What the FDA Keeps Seeing

After analyzing hundreds of warning letters, experts have found patterns. These aren’t random errors-they’re the same failures, over and over.

• Inadequate investigation of out-of-specification (OOS) results: Found in 63.4% of letters. If a drug test comes back wrong, you can’t just ignore it or retest until you get a good number. You have to find out why.
• Lack of quality unit oversight: 57.8% of letters. The quality team must be independent, empowered, and involved in every decision. Too many companies treat them as paperwork clerks.
• Aseptic processing failures: 78.3% of letters for sterile products. This includes bad media fills, unsterile equipment, and poor gowning procedures. One 2022 study found 41.6% of these letters cited failed media fill tests-meaning the company didn’t prove their sterile process actually works.
• Data integrity issues: Up from 42% in 2019 to 67% in 2023. That means deleted files, backdated logs, or not recording raw data. The FDA now checks electronic systems like it’s a forensic audit.

One letter to Creative Essences, Inc. in September 2025 specifically called out failure to test incoming glycerin and propylene glycol for diethylene glycol-a toxic contaminant that’s killed people in the past. That’s not a technicality. That’s life or death.

Who Gets Warning Letters-and Why It’s Unequal

It’s not just about violations. It’s about who’s being inspected and how.

In 2022, Indian manufacturers received 38.7% of all warning letters (112 out of 289). U.S. companies came second at 31.5%. But here’s the problem: a 2022 Government Accountability Office report found that similar violations at two different facilities sometimes got different responses-one got a warning letter, the other got just a Form 483.

And foreign facilities? They’re 22% more likely to get a warning letter than U.S. ones for the same problem. That’s not just about standards. It’s about perception, resources, and pressure.

Small companies feel this the hardest. One Reddit user, u/QualityAssurancePro, said their 15-person team had to hire three consultants at $250/hour just to write a response. The cost nearly bankrupted them. Meanwhile, big pharma has entire departments dedicated to FDA compliance.

What Happens After You Get a Warning Letter

Getting the letter is only the beginning. The real work starts now.

The FDA gives you 15 working days to respond. That’s not a suggestion. It’s a deadline. And your response has to be perfect.

Effective responses include:

• Complete root cause analysis-with data, not guesses
• Proof that the fix actually works (e.g., new media fills, revalidated processes)
• Updated procedures with signatures and training records
• Timeline for full implementation

Companies that respond well can recover. Teva Pharmaceuticals fixed a warning letter at their Israeli plant in just 11 months. They reduced product defects by 30% and got off the import alert list.

But most don’t. A 2023 survey found that 68% of companies had to pause new product submissions while fixing the issue. The average delay? 8.7 months. One company lost $28 million in revenue because their ophthalmic drug launch was delayed by 14 months.

Costs are brutal. EY’s 2023 survey found the median cost to fix a warning letter: $1.8 million for U.S. facilities, $2.7 million for foreign ones. That’s not just labor-it’s new equipment, training, audits, and consultants.

The Bigger Picture: Why the FDA Is Cracking Down

The number of warning letters has jumped 92% since 2018. Why now?

The FDA’s budget for foreign inspections rose from $87.7 million in 2020 to $112.7 million in 2023. They’re sending more inspectors overseas. They’re using new tools to check data integrity. They’re prioritizing facilities with past violations.

Their 2023-2027 Strategic Plan says they want to reduce repeat violations by 25% by 2027. That means they’re not just punishing mistakes-they’re trying to force companies to change their culture.

But there’s a risk. A 2023 FDA inspector general report found that 31% of follow-up inspections were delayed past the 6-month target. That means some companies get a warning letter, pay for fixes, and then the FDA doesn’t check back for a year. During that time, the problem could come back.

And small manufacturers? They’re caught in the middle. The system works great for big companies with compliance teams. But for a 20-person factory? One warning letter can be existential.

What You Need to Do If You’re in Manufacturing

If you’re making drugs, even in a small facility, you need to treat CGMP like your life depends on it-because it does.

Here’s what actually works:

1. Don’t wait for an inspection. Do internal audits every quarter. Look for the same things the FDA does.
2. Train your quality unit like they’re the last line of defense. They need authority, access, and time-not just a title.
3. Fix OOS results properly. Don’t retest until you get a pass. Investigate. Document. Prove it.
4. Protect your data. If you’re using electronic systems, make sure logs can’t be edited or deleted. Audit trails aren’t optional.
5. Practice sterile procedures like your life is on the line. Because it is. Media fills aren’t paperwork-they’re proof.

The FDA isn’t trying to shut you down. They’re trying to make sure your medicine doesn’t kill someone. But if you ignore the rules, they will act. And when they do, the cost isn’t just financial-it’s reputational, operational, and sometimes, human.