In this post, I’ll share the key trends from recent FDA warning letters and 483 observations – and how you can stay ahead of those risks.
You’ll gain specific strategies to enhance your quality systems, improve your investigation processes, and better manage your contract manufacturers before the FDA knocks on your door.
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Quality Control Unit responsibilities remain the number 1 most cited issue for the fifth consecutive year, with 483 citations. This is closely followed by inadequate investigations and insufficient written procedures.
These persistent patterns aren’t coincidental – they reveal exactly where FDA inspectors focus their attention during site visits.
When I look at warning letters from the past few years, I see the same issues coming up repeatedly. The FDA clearly expects organizations to have these basics in place, yet many companies still struggle with them:
Recognizing these patterns lets you focus your resources where they matter most – on the areas that could trigger FDA scrutiny – rather than trying to fix everything at once.
When FDA inspectors examine your quality systems, they’re looking beyond your documentation. They want to see evidence that your Quality Unit has genuine independence and authority.
Back in 2023, I witnessed this firsthand during an audit of a mid-sized pharmaceutical company. The FDA inspector spent nearly a full day tracing decisions through their quality system, looking specifically for instances where the Quality Unit had overruled production priorities. The lack of such examples became a major finding.
In another case, the FDA raised concerns about an organizational structure where the Head of Quality reported to the Head of Operations. While quality and operations must integrate somewhere in the organization – as not everyone can report directly to the CEO – the critical issue is ensuring the Quality Unit maintains its independence to make decisions free from production pressures, regardless of the reporting structure.
To avoid this finding at your company:
Most importantly, ensure your senior management visibly supports quality decisions, especially when they impact timelines or costs. After 25 years in the industry, I can tell you that management support can make the difference between an inspection pass or fail.
Once you’ve established proper quality oversight, the next area the FDA will scrutinize is how you handle problems when they occur. This is where the second most common observation comes into play: inadequate investigations.
Think of a deviation like a crime scene. The longer you wait to investigate, the colder the trail becomes. A quick response is essential to finding the true cause.
I’ve seen too many companies wait days or even weeks to begin investigating, by which time important evidence has disappeared. The companies that perform best in FDA inspections typically have “SWAT teams” that begin gathering evidence within 24-48 hours of an event and select a lead investigator.
When you discover a deviation, you need to:
This last point is particularly important. The FDA increasingly expects to see effectiveness verification, even though this is not explicitly stated in 21 CFR 211. In a recent warning letter, they specifically criticized a company for implementing corrective actions without ever checking if they worked.
Investigations rely on well-documented processes. This brings us to the third most common observation: insufficient written procedures.
Are your procedures only in your employees’ heads? The question isn’t whether your experienced staff knows what to do – it’s whether a new employee could perform the task correctly using only your written procedures.
I recently worked with a company whose operators had been performing a complex sampling procedure for years. When I asked to see the SOP, it contained just two sentences. The operators knew what to do through oral tradition, but this created an enormous compliance risk. Sure enough, when the FDA came in, this was one of their first findings.
Take action now by reviewing your SOPs with fresh eyes. Bring in someone from another department to try to follow them. If they struggle, your procedures need some improvement.
Even with strong internal systems, your compliance chain is only as strong as its weakest link. This is why the FDA has increasingly focused on contract manufacturing relationships.
The question you need to ask is more specific than many realize: Do you know what else your CMO manufactures on the same lines as your products? You need to find out before the FDA does.
A particularly concerning trend involves shared equipment for pharmaceutical and non-pharmaceutical products. In 2024 alone, the FDA issued eight warning letters to companies manufacturing drugs with the same equipment used for industrial chemicals, detergents, and even automotive brake cleaner.
Before your next CMO audit:
The FDA once inspected a CMO that was manufacturing an injectable product on the same line they used for household cleaners. The client was perhaps unaware of this, but the FDA discovered it during their inspection, resulting in a warning letter that led to millions in lost revenue and a scramble to find a new manufacturing partner.
This highlights the FDA’s view on CMOs: “We consider CMOs an extension of your own facility.” So your oversight should be equivalent, even if your manufacturing is located on the other side of the globe.
While all the areas we’ve discussed are important, certain violations are so serious that the FDA will take immediate action. In my career at Novo Nordisk and now as a consultant at Epista, I’ve seen these “showstoppers” bypass the normal observation process and trigger warning letters or import alerts right away.
Even if you have sophisticated electronic systems and detailed procedures, don’t overlook these fundamentals:
Issues like peeling paint in a clean room can trigger regulatory action if they suggest poor facility controls. A recent warning letter to an Indian manufacturer cited exactly this issue, resulting in import restrictions that cost millions.
Now that you understand the key risk areas and how they interconnect, it’s time to build your proactive compliance strategy. This approach ensures you tackle the FDA’s key concerns before they turn into costly compliance issues.
I recommend a five-step approach based on what I’ve seen work for companies across the industry:
First, evaluate your Quality Unit’s independence and authority. Do they have the resources and management support needed to fulfill their responsibilities effectively? Can they make difficult decisions without interference from production?
Next, strengthen your investigation procedures. Are you responding quickly to deviations? Do you have trained personnel who can conduct proper root cause analyses? Are you verifying that corrective actions actually work?
Then, review and enhance your documentation. Ensure your SOPs are clear, detailed, and reflect actual practice. Remember, as far as the FDA is concerned – if it’s not written down, it didn’t happen.
For companies working with CMOs, intensify your oversight program immediately. Remember: The FDA considers contractors an extension of your own facility – you can’t outsource regulatory responsibility.
Finally, schedule regular “fresh eyes” assessments of your facilities and procedures. External perspectives often help to spot issues that internal teams miss through familiarity.
Stay ahead of the FDA inspectors by addressing their focus areas before they arrive. By taking action now, you’ll reduce compliance risks and walk into your next inspection with confidence.
The patterns in recent warning letters offer a clear compliance roadmap, whether you’re facing your first inspection or your fiftieth. FDA inspectors will be looking closely at these areas. The real question is: Will your team be prepared?
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