Monday, July 2, 2012

Commercial Cell Culture, cGMP and 483s

So when I was at Cornell studying to be a biological engineer and then switching over to chemical engineering, I figured that my career in life would be a biochemical engineer. That was the hot new thing and even the School of Chemical Engineering within the College of Engineering at Cornell changed their name to the The School of Chemical and Biomolecular Engineering.

You learned about fermentation, cell culture, bioreactors and weird hosts like plant-cell culture and insect baculovirus. But what they never got to was cGMP... they had classes on it, but it was very much an outsider's perspective.

GMP Regulations in the real-world

When you get to the real world, drug firms manufacturer under the reign of terror known as cGMPs. The way it works is this:
  • By law, drug manufacturers whose products make it into the US markets must register with the FDA.
  • FDA issues a Form 482 and presents credentials when they inspect your plant
  • Should there be inspectional observations, the FDA inspectors issue a Form 483 detailing your manufacturing risks
  • If these observations are not addressed and the problems sufficiently serious, the FDA issues a warning letter.
  • If the issues remain unaddressed, the FDA gets a consent-decree to seize product or shutdown your plant.
If you run cell culture processes to make food or drug products sold in the US... and you are conscientious about getting your product to market, you have no choice but to maintain a high degree of compliance with the GMP regulations as well as be aware of the FDA's emphasis.

Where to put your resources?

The key is to focus on items as far upstream of the consent decree as possible. So between addressing the warning-letters vs. the non-binding 483 observations, the vast majority of QA Pharma professionals focus on the dreaded 483.

The deal with the 483s is that the FDA issues a lot of them and cannot release unredacted versions of the inspectional observations. Requesting 483s from the FDA can take months.

FDAzilla offers FREE 483s!!

This is where FDAzilla steps in; FDAzilla is a website that provides FDA intelligence and is coming up with a 483 store and service. They've already organized all the free 483s from into a Dropbox folder.

I checked it out over the weekend on my iPad. You can read Novartis 483s as fast as you read emails:
free 483s

Here's the Genzyme's infamous 2009 Form 483. The free ones are the most-requested or deemed a public interest by the FDA.
dropbox fda 483s

Here's another view of a (Gilead) 483:
ipad 483s fda

There are over 500 documents in this Dropbox folder and access is free (well, you need to leave an email address to whom they grant the access).

Sign up for FREE FDA Form 483s

From the QA professional that needs these resources to the kept-in-the-dark cell culture engineer, if you work in the cGMP field, you really ought to look into access to this FDAzilla resource.

p.s. - Tony, CEO of FDAzilla, tells me there's a surprise in store, so stay tuned.

No comments: