

by Oliver Yu For one, they run proprietary processes: it's none of our business. For two, Obamacare forces the FDA to approve a regulatory pathway for biosimilars: why share these growing pains with competitors who seek to eat their marketshare? For three, why air out dirty laundry?

Visual examination of cell culture indicates contamination of seed cultures

Gram stain shows no bacteria

5-day incubation with standard plate count shows no growth

No signs of contamination by looking at dO2, pH trends

No evidence of contamination from standard QC testing methods

This contamination is the black swan event. Never in the history of cell culture manufacturing has anyone encountered a microbe that isn't detectable with standard methods.

Leptospira

0.1 micron in diameter - CAN PASS THROUGH 0.1 micron filters!

Non-spore former - Not heat resistant

heat resistant Requires long-chained fatty-acid - Will not grow in media alone, requires presence of CHO cells





For us, we would be wise to learn their lessons, which are:



There's a bug out there that passes through 0.1 micron filters: L. licerasiae

This bug (and related bugs) are not detectable with standard methods, so LOOK at your cultures!

Update control strategies (consider heat-treatment and other barriers) Battling contaminations is bad enough. Now there's a bug out there that can get by sterile media filters and cannot be detected by no other method than by putting your eyeballs on it.

The remainder of the slides go through their root cause analysis and contamination investigation as well as global risk assessment (i.e. "CYA"). And it's certainly worth a gander.For us, we would be wise to learn their lessons, which are:

A year ago on July 19th, 2012, Genentech VP of Biologics Quality(Anders Vinther) presented "A Novel Bacterial Contamination in Cell Culture Manufacturing" at the West Coast Chapter of the Parenteral Drug Association . (This same presentation was likely made elsewhere, but the only "Google-able" mention of it was on the WCC PDA website).Most biotech/pharma companies are tight-lipped about their biologics manufacturing process problems.So when Genentech came forward with a very detailed presentation on bioreactor contamination and a prescription for how the rest of the biotech industry to handle this specific type of contamination, it's worth paying attention.Their summary of events goes like this:After a second seed bioreactor contamination, Genentech was able to cultivate the bug and identify it as Leptospira. Leptospira is a coiled/spiral that survives in soil and water. It is motile, slow-growing obligate aerobe that favors liquid environments.But the characteristics relevant to biologics manufacturing are: