by Tony Chen
Okay, let’s settle this once and for all. This week, we will be writing a series of posts that will give you an industry primer for what these Form FDA 483s are, why they’re important, how to avoid them, and how to respond to them. Today, we cover the basics. Some of you pros out there know this stuff all too well.
What is a Form FDA 483?
The FDA has authority to inspect factories that manufacture products regulated by the FDA. FDA inspectors can come in and inspect any given facility at any time, and they essentially write down their observations on a form called Form FDA 483s (or just 483s for short). Read Wikipedia’s entry on 483s for more background. We’ve published a list of 483s issued by the FDA over the last 10 years.
What’s in a Form FDA 483?
The best way to tell you is to show you. Visit the FDA’s ORA FOIA reading room for a sample of 483s that the FDA makes available publicly. But basically, you’ll see these fields in a 483:
- Issuing FDA field office and address – as of now, there are 5 regional offices and 20 district offices.
- Dates of inspections – can be 1 day, or I’ve seen them go up to several months.
- FEI number – stands for the Firm Establishment Identifier, a number created by the corresponding district office
- Manufacturer’s contact info (no fun being this person, right?)
- List of Observations. Typically, there’s somewhere between 5 and 10, though I’ve seen some with 58+ (ouch…).
- Names and titles of the investigators – usually 1 or 2. One unfortunate pharma manufacturer got to host 11 of them.
What’s the difference between a Form FDA 483 and a warning letter?
Bad inspections lead to Form FDA 483s. Warning letters are a notch higher than Form FDA 483s – they usually result from multiple lacking responses to issued 483s, or other issues much more serious that require quick attention/escalation. 483s tend not to make the press (more on how available they really are in a second), whereas warning letters posted on the FDA website usually make the industry news section.
And so long as we’re getting all the terminology right, there’s one more report type to be aware of, the EIR (Establishment Inspection Report). This is a more detailed play-by-play description of the inspection, written by the inspector. Think of the 483s as an executive summary (i.e. here’s the 10 key items) and the EIR as the inspector journal (i.e. “and then I talked to Peggy Smith, Associate Director of Regulatory Affairs, and she was responsive to our information requests”).
Why are Form FDA 483s important?
Companies that receive a Form FDA 483 should respond within 15 days. It’s not required, but ignore 483s at your peril. Some professionals have wondered if 483s have lost their bite, comparing them to a parent “warning” their child of impending punishment (but then never following through with the punishment). While companies do not fear 483s as they may have a generation ago, they are still extremely serious. One company I talked to told me that they end up spending around $200,000 to $250,000 addressing one 483. They move mountains – generating documentation, changing processes, initiating new rounds of training, altering reporting structures – to show the FDA that they are on the ball. The last thing a company wants is for the FDA to follow up with a warning letter or even force a plant shut-down.
One of my friends walked through a parking lot at a big pharma company and there sat a nice Porshe 911 with license plate “zero 483s.” Guess they had a good year.
Ballpark, how many Form FDA 483s does the FDA issue?
Good question, and we can do a lot better than ballpark. You can actually figure this out through our Form FDA 483s listing database. In 2010, 9,910 Form FDA 483s were issued by the FDA. This is a huge bump up (20-25%) from 2007/2008, and an all-time high for the data we have available (2000-2010)
FDAzilla 483s Resource Center:
- Form FDA 483s: 3 Types of Inspections
- What’s the big deal about these Form FDA 483?
- Who can see Form FDA 483s, and where do I get them?
- How to Respond to a Form FDA 483
- What have you learned from reading Form FDA 483 observations?
- Form FDA 483s listing, 2000 to present
- Form FDA 483s Store
- FDAzilla Report: Top Seven Strategies to Avoiding 483s