Vaccine Manufacturing Woes at Emergent

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The New York Times has a good story on the problems at the Emergent vaccine plant in Baltimore, following up on this one. They’ve uncovered a report from last summer that warned that the facility had quality control problems:

A copy of the official’s assessment, obtained by The New York Times, cited “key risks” in relying on Emergent to handle the production of vaccines developed by both Johnson & Johnson and AstraZeneca at Emergent’s Bayview plant in Baltimore.

The assessment, which has not been released publicly, was based in part on a visit to the plant just days after the government awarded Emergent a contract worth up to $628 million, mostly to prepare its factories to make coronavirus vaccines as part of Operation Warp Speed.

Addressing the problems “will require significant effort,” and the company “will have to be monitored closely,” said the report, which was written by Carlo de Notaristefani, a manufacturing expert who has overseen production of Covid-19 vaccines for the federal government since last May. Though marked as a draft, federal officials said the report was considered to be final.

You’d think that this visit might have been even more useful before the contract was awarded, but Emergent has been contracting with the government for vaccine production since 2013. But apparently the problems are longstanding as well – here’s a bit from the earlier Times story:

An audit conducted for AstraZeneca specifically highlighted the risks of viral cross-contamination, which experts believe was responsible for tainting the millions of Johnson & Johnson doses, according to a review of the confidential document by The Times. The audits and investigations also flagged a persistent problem with mold in areas required to be kept clean, poor disinfection of some plant equipment leading to growth of bacteria, the repeated approval of raw materials that had not been fully tested, and inadequate training of some employees.

The current theory is that the recent J&J production run was lost because an employee did not adequately disinfect while moving from the AstraZeneca section of the plant into the J&J section. That would most certainly do it. Anyone who’s done biologics production (or who has just worked in a busy cell culture lab) will be able to tell you stories about contaminations of this sort, some disastrous and some narrowly avoided. It’s even worse than mistaking the sugar for the salt in a kitchen, because you’re dealing with things that grow and reproduce – cells and viruses. A mixup can spread catastrophically, and that’s just what seems to have happened here.

And if the hygiene at this plant is as depicted above, they’re asking for other kinds of contamination as well. Things like adventitious yeast can rip up your cell cultures, too. In research labs, people are warned about doing any home baking or brewing, and to be sure to take serious showers before setting foot in the cell culture room after anything like that. There are mycoplasma out there ready to drop in and mess with your cells, there are viruses that you haven’t even heard of before that can ruin everything (ask Genzyme people about that). . .no, cell culture work is pretty unforgiving, and the larger the scale, the larger the worries. There is only one way around this problem, and that is rigorous cleanliness. No shortcuts, no exceptions. And walking from a part of a production plant that is dealing with one kind of cell/virus combination into a part that’s dealing with a completely different one without even taking a shower is not rigorous cleanliness.

The Times reports that Emergent’s own auditors had repeatedly detected mold in a cell culture room, repeatedly had problems with bacterial growth on equipment surfaces, and so on. This stuff will happen anywhere if you are not a complete hardass about disinfection, and if you’re running a vaccine production facility there is no excuse not to be. Fungi and bacteria never take breaks and they are the living, metabolizing definition of “opportunistic”. This attitude does not help:

But four former company officials, speaking on the condition of anonymity because they had signed nondisclosure agreements or feared retaliation, described an environment where top Emergent leadership tolerated and even encouraged the flouting of federal standards for manufacturing and marketing products.

One of the former officials said that as the company scrambled to meet the heavy demands of vaccine production, a senior manufacturing supervisor often responded to reports of quality errors by asking: “Do you want me to make drugs or fix issues? I don’t have time to do both.”

The cure for this is to stop telling your partners and clients that you can deliver on these demanding schedules when you actually can’t. That’s how you get a culture of sweeping things under the rug, because you end up having to lie (and to make others lie) in order to meet the targets you’ve publicly agreed to. You see it in industry when a toxic environment sets in over in sales and marketing: “Make your numbers or I’ll find someone who will” and all that. But trying this tough-guy business when you’re up against the constraints of science and engineering is particularly idiotic. This is the “take off your engineer hat and put on your management hat” attitude that helped blow up the Challenger space shuttle, and it’s helping to blow up vaccine production in Baltimore.

I see that J&J has taken over management of the facility, and I wish them good luck fixing these problems. We – the US and the world – need this production facility running the right way, but having it full of corner-cutting managers and overworked employees is not that way. Better to scale down the production targets and get them right, at least for now, than to run on the edge of disaster.

 

The post Vaccine Manufacturing Woes at Emergent first appeared on In the Pipeline.