If you're manufacturing a product that is regulated by the Food and Drug Administration, be it a food, a drug, a medical device, an X-ray machine, or a condom, you are subject to inspection by the FDA.
There's what I call an FDA Enforcement Funnel.
At the top of the funnel are cGMP facilities that get inspected. Inspectors come by, they audit your facility, they find nothing to worry about and they leave. You can sigh relief and be on your way. They'll be back in more or less 2 years.
The next step down this funnel is when the audit generates observations. Inspectors will write these observations down in what's called a Form 483... a.k.a. ("483"). As the recipient of the 483, the ball is in your court. You need not actually respond, but responding is actually a pretty good idea because your well-reasoned, timely response can help you avoid a warning letter.
An FDA warning letter is a communication that the Food and Drug Administration is serious and they will seek enforcement action. You'll get these if your inspectional observations are serious enough... or if repeated inspections reveal no actions are taken to assuage the FDA that you're taking quality seriously.
If the warning letter produces low-impact results, the FDA will use the weight of law to coerce you into compliance via a Consent Decree... where in lieu of legal action, they get you to volunteer... in writing... to fix your compliance problems.
In biologics manufacturing, getting a 483 is the first step down the slippery slope of FDA enforcement action. You're not going to be dealing with consent-decrees if you haven't gotten warning letters. You're not getting warning letters about cGMP issues if you haven't gotten 483s. So focus on not getting 483s.
How do you avoid 483s? Well, there are armies of QA and regulatory professionals trying to answer that question.
One way is to get some intel on the 483s that the FDA has previously issued. The FDA releases a limited set of redacted 483s here. These 483s are scanned PDF files that are often requested or in the news (remember the 2012 Eggs or 2013 Pharmacies?)
What if a 483 you're interested in isn't there? Well, you can submit a Freedom of Information Act (FOIA) request to the FDA, fill out their form, email back and forth with an FOIA specialist and get your PDF file in several weeks.
- or -
You can browse the FDAzilla 483 Store to search for a 483... or even browse 483s by inspectors to get a sense of where each inspector likes to focus.
As my QA brethren (Thats you, Barlow and Zucca) like to remind me, producing successfully harvested cell cultures isn't the point. Producing releasable lots of drug product is; and producing releasable lots means compliantly (as deemed by the FDA) operating a GMP environment.
See also:
There's what I call an FDA Enforcement Funnel.
At the top of the funnel are cGMP facilities that get inspected. Inspectors come by, they audit your facility, they find nothing to worry about and they leave. You can sigh relief and be on your way. They'll be back in more or less 2 years.
The next step down this funnel is when the audit generates observations. Inspectors will write these observations down in what's called a Form 483... a.k.a. ("483"). As the recipient of the 483, the ball is in your court. You need not actually respond, but responding is actually a pretty good idea because your well-reasoned, timely response can help you avoid a warning letter.
An FDA warning letter is a communication that the Food and Drug Administration is serious and they will seek enforcement action. You'll get these if your inspectional observations are serious enough... or if repeated inspections reveal no actions are taken to assuage the FDA that you're taking quality seriously.
If the warning letter produces low-impact results, the FDA will use the weight of law to coerce you into compliance via a Consent Decree... where in lieu of legal action, they get you to volunteer... in writing... to fix your compliance problems.
In biologics manufacturing, getting a 483 is the first step down the slippery slope of FDA enforcement action. You're not going to be dealing with consent-decrees if you haven't gotten warning letters. You're not getting warning letters about cGMP issues if you haven't gotten 483s. So focus on not getting 483s.
How do you avoid 483s? Well, there are armies of QA and regulatory professionals trying to answer that question.
One way is to get some intel on the 483s that the FDA has previously issued. The FDA releases a limited set of redacted 483s here. These 483s are scanned PDF files that are often requested or in the news (remember the 2012 Eggs or 2013 Pharmacies?)
What if a 483 you're interested in isn't there? Well, you can submit a Freedom of Information Act (FOIA) request to the FDA, fill out their form, email back and forth with an FOIA specialist and get your PDF file in several weeks.
- or -
You can browse the FDAzilla 483 Store to search for a 483... or even browse 483s by inspectors to get a sense of where each inspector likes to focus.
As my QA brethren (Thats you, Barlow and Zucca) like to remind me, producing successfully harvested cell cultures isn't the point. Producing releasable lots of drug product is; and producing releasable lots means compliantly (as deemed by the FDA) operating a GMP environment.
See also:
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