Johnson & Johnson Covid-19 vaccine is delayed by a U.S. factory mix-up.

[BumRushDaShow]

Source: New York Times

Workers at a Baltimore plant manufacturing two coronavirus vaccines accidentally conflated the vaccines’ ingredients several weeks ago, ruining about 15 million doses of Johnson & Johnson’s vaccine and forcing regulators to delay authorization of the plant’s production lines. The plant is run by Emergent BioSolutions, a manufacturing partner to both Johnson & Johnson and AstraZeneca. Federal officials attributed the mistake to human error.

The mixup has halted future shipments of Johnson & Johnson doses in the United States while the Food and Drug Administration investigates. Johnson & Johnson has moved to strengthen its control over Emergent BioSolutions’ work to avoid further quality lapses. The mistake is a major embarrassment for Johnson & Johnson, whose one-dose vaccine has been credited with speeding up the national immunization program.

It does not affect Johnson & Johnson doses that are currently being delivered and used nationwide. All those doses were produced in the Netherlands, where operations have been fully approved by federal regulators. But all further shipments of the Johnson & Johnson vaccine — projected to total tens of millions of doses in the next month — were supposed to come from the massive Baltimore plant. Those shipments are now in question while the quality control issues are sorted out, according to people familiar with the matter.

Federal officials still expect to have enough doses to meet President Biden’s commitment to provide enough vaccine by the end of May to immunize every adult. The two other federally authorized manufacturers, Pfizer-BioNTech and Moderna, are continuing to deliver as expected. Pfizer is shipping its doses ahead of schedule, and Moderna is on the verge of winning approval to deliver vials of vaccine packed with up to 15 doses instead of 10, further boosting the nation’s stock.

Read more: https://www.nytimes.com/2021/03/31/world/johnson-and-johnson-vaccine-mixup.html

---

This was one of the (contract) companies making the vaccine locally in the U.S. for J & J. The other was actually done by Janssen, which is a J & J's subsidiary (and originator).

[soothsayer]

1. Don't screw up Joe's goal, y'all

[Wingus Dingus]

2. Jesus Christ. Can't get the recipe right.

You gotta be kidding me.

[appalachiablue]

3. Get it together Baltimorons, come on now

[WarGamer]

4. Massive. Clusterfuck.

[Yo_Mama_Been_Loggin]

5. Oops

Glad they caught this.

[In_The_Wind]

16. I agree.

[Raven123]

6. Hard to imagine no one checked earlier in the process, but it is what it is.

[Yavin4]

27. Exactly. Don't wait until the car gets to the end of the assembly line to check for problems.

There should be quality checkpoints starting the very beginning.

[winstars]

7. Hate to look at it like this but some extra people may die because of this screw up.

Less vaccine equals less people vaccinated and less people vaccinated means more available host bodies....

Like in Europe.

[BumRushDaShow]

8. In this case

Since Janssen only recently got EUA approval, their vaccine has made up a much smaller percentage of the total approved vaccines in the U.S. at this point and they are only now really ramping up the processes (with this little firm helping as a domestic partner).

The agreement recently announced between J & J and Merck, with Merck's big vaccine facilities in NC designated for that production, may end up with Merck being the one that will provide the bulk of the doses of this vaccine once they are up and running.

[winstars]

9. If 15 million doses got "ruined" then thats 15 million less available in April? Yes?

May, June and July is when the Merck made vaccines will hit from what I have read.

The article makes it sound like these 15 million vaccines were almost good to go...

[BumRushDaShow]

10. I don't think this company was approved to ship yet

There is a process for review and approval of their GMPs and I expect there will be some major work that will need to be done before they would be given the go-ahead to ship. This is one of the issues that comes about when you "rush" some of these companies to get something out.

The NYT had sent out a "correction" breaking news banner to their earlier "breaking news" banner (although it didn't really change the article headline or content) regarding this firm being on hold for being able to ship "future" doses vs the availability of Janssen doses overall.

I.e., this is not impacting the current shipments that we are getting for this vaccine from overseas (where Janssen is making them and shipping them here).

[GopherGal]

20. Yeah, it sounds as if it got nowhere near anyone's arm...

I think this was manufacture of the active ingredient/drug substance, which is extensively tested for quality (which this lot apparently failed) and would subsequently be shipped (likely to another site) for fill/finish into "drug product" which would also undergo extensive testing before labeling/packaging and distribution. So there were plenty of steps yet to go before this tainted material got to patients.

There don't seem to be a lot of details out yet.

It says the site isn't approved for making the vaccine yet. So possibly it was during one of the "conformance lots" that need to be successfully manufactured (and pass all release testing, plus often additional characterization testing) to demonstrate to regulators (FDA) the safe manufacture of the product before you can get permission to distribute product from the facility. Often the material from these lots can be held, pending approval, and marketed after the fact, so there is potential effect on the vaccine supply, but it may be several weeks/months down the line.

There will probably be additional training for employees to verify material ids before use and some sort of improvement to the processes for change-over and segregating their materials. (This can be tricky when multiple materials require special storage conditions - imagine segregated cages inside walk-in cold chambers or somesuch.)

Quite a few somebodies having some tough days at work at Emergent. And more than a few J&J experts suddenly booked into hotel rooms in the Baltimore area with the intent of (socially distantly) breathing down Emergent's necks for the next couple months.

[BumRushDaShow]

21. I forgot where I saw it

(may have been a news report) but there was a video showing the stages (steps) that were part of the process of manufacturing vaccines - the example they showed was for the mRNA ones, although I know J & J's (Janssen's) is an adenovirus-derived one instead.

They hadn't gotten to the finished product stage yet to do any vial-filling and the last report I heard this morning was that Emergent was ALSO doing AstraZeneca manufacturing scale-up.

So it sounds like "someone" may have confused the processes/batch requirements for J&J's vaccine, with AstaZeneca's vaccine.

Always happens around "holidays". Team Biologics is gonna be busy this weekend.

[GopherGal]

22. Yes, I saw that too.

We're working off a pretty hazy description. They're doing pretty poor GMP document control if they don't have clearly marked records telling what goes into the batch. Maybe they should be putting them in color-coded binders or something like that which might make it clear to an observer across the room that they were referring to the wrong binder ("Hey! What's that green binder doing in here? We're making J&J's vaccine in here. We use the batch records in the orange binders!" )

They're not telling us much about what level of ingredient mix up it was. If it was the output of step 1 of AZ's process was stored in the same room as the intermediate output of J&J's process and the wrong one was grabbed for subsequent processing, that's a pretty gross error. If it was "the process calls for sodium phosphate monobasic but we used the sodium phosphate dibasic that we had on the shelf to use in AZ's process" that's a little easier mistake to make, even if you have the correct "recipe" in front of you. The difference between Na2HPO4 vs NaH2PO4 might slip by the checker who was supposed to be verifying everything used. But you'd think a multi-product contract facility would have some ergonomic steps in place to prevent this.

[BumRushDaShow]

24. You would think they would have segregated the 2 vaccines in separate process rooms

I don't know how big that facility is but perhaps they have those tanks in one huge room and segregate the different contracted vaccine orders, with their bulk reagents in the same "designated " areas.

However if both use the same bulk reagents but use different dilutions of them and that wasn't clearly marked, then

All of that stuff needs to be labeled and tracked in logs (I would think they barcode all of that stuff).

But unfortunately cGMP screw-ups are not uncommon - at least for drug products. I can imagine that biologics - particularly something new like this attempted by a smaller firm, is probably even more an issue.

[LisaL]

26. They mixed up the vectors (per NYT article).

Both J&J vaccine and AstraZeneca use adenoviral vectors to make the vaccine, but the vector for AstraZeneca are different from that for J&J. Sounds like they used a vector for AstraZeneca while making J&J vaccine. So it would have been AstraZeneca and not J&J. And AstraZeneca is not even approved in the US, and it takes two doses, and then there is a issue of side effects (blood clots).

[BumRushDaShow]

30. Well now that is a mess!

Maybe they should save some of that and continue processing it on a small-scale to see what the result is... Sometimes "break-throughs" come out of errors like that. I expect the diluents (buffers, etc) might be slightly different between the two vaccines.

And it's bad enough that AstraZeneca already had to have their data-reporting corrected "publicly", so they might want to consider another contract manufacturer for their product too, because I expect this firm is not going to be ready for approval any time soon (at least based on what I heard on the local radio news station here).

Link to tweet

TEXT

Mike Hellgren
@HellgrenWJZ
·
Jan 26, 2021
A look at where the Johnson and Johnson vaccine will be produced in Baltimore; the containers in the back have disposable linings that can be changed out. Once approved, the vaccine will only require one shot. @wjz
Image

Mike Hellgren
@HellgrenWJZ
Cell cultures are grown in sterile bags then infected with the virus—it will be purified and eventually forms the vaccine that will be put into the dose bottles @wjz
Image
3:07 PM · Jan 26, 2021

I also found this gem -

Quality control issues force Johnson & Johnson to scrap doses of COVID-19 vaccine

Updated on: April 1, 2021 / 2:12 PM / CBS/AP

(snip)

But it could be at least two weeks until all of the vaccine produced for Johnson & Johnson in Baltimore — including three lots manufactured after the discarded batch — are cleared by the ongoing investigation, which federal officials believe is the main remaining hurdle before Emergent's vaccine factory can be cleared by regulators.

Vaccine manufacturing is a complex process and discarded batches are not uncommon, especially in the early stages of production. However, errors invite extra scrutiny from both the company and regulators to trace how the lapse occurred and ensure the mistake won't be repeated.

Emergent's revenues skyrocketed during the Trump administration, jumping from around $523 million in 2015 to more than $1.5 billion in 2020. The company has invested heavily in lobbying the federal government, according to disclosure records, which show the company spent $3.6 million on lobbying in 2020 alone.

(snip)

The Associated Press reports that Emergent has been cited repeatedly by the Food and Drug Administration for problems such as poorly trained employees, cracked vials and mold around one of its facilities, according to records obtained by the AP through the Freedom of Information Act. The records cover inspections at Emergent facilities since 2017.

https://www.cbsnews.com/news/quality-control-issues-force-johnson-johnson-to-scrap-doses-of-covid-19-vaccine/

Apparently AP did an FOI on FDA's EIRs for them from the past.

[LisaL]

25. Per NYT article, they mixed up the actual vectors.

So to me it appears they made AstraZeneca instead of J&J, and labeled it as J&J. Lovely.

[GopherGal]

31. Holy cow! That's a pretty huge error!

This is gonna be a case study in every biopharmaceutical company's Good Manufacturing Practice annual update training next year.

But I find it pretty astonishing that this happened. At a minimum, any batch documentation I've ever seen requires the operator to sign that they've added the correct ingredients and a "checker" must also sign that they verified. Maybe if they're just doing a trial run, they aren't using final documentation and skipped the verification step?? But with millions of doses of vaccine on the line, most QA & management would want to document as well as possible with the hope that the resulting material could eventually be converted to commercial production, so would be unlikely to use any precious ingredients (or, for that matter, plant time) without using near-final documentation.

Fortunately, the federal (and international) guidelines for product specifications pretty much require a sequencing test to verify the identity of the product before release.

[iluvtennis]

11. This is very scary. Feds needs to review and approve the quality

control measures. Peoples lives are on the line snd we can’t have tainted vaccines.

[LisaL]

15. That facility is not yet certified to make J&J vaccine.

This incident is probably not going to help it to get certification.
I don't know what they mixed up in there, but it's not good.

[FakeNoose]

12. I wonder if this is sabotage?

[BumRushDaShow]

13. I think

it is just poor cGMPs. They are going to be swarmed...

[Steelrolled]

23. It could be sabatage by Trump and the Republicans,

or it could be gross incompetence by Biden and the Democrats. There is no way such a mistake could be made without political influence. /s

[PoliticAverse]

14. Don't conflate the streams! n/t

[totodeinhere]

17. This really upsets me.

I wonder how many innocent lives will be lost due to this unacceptable and stupid "mistake." Heads should roll over this.

[BumRushDaShow]

18. Well this was one of the contract sites that was to help provide

a "domestic" source of J & J's vaccine. Apparently this company was also starting production of AstraZeneca's vaccine for future "domestic" distribution, since AstraZeneca is gathering their documentation to request an EUA for use in the U.S., and AstraZeneca's vaccine is currently made overseas.

So it sounds like they mixed up the process specs for the 2 different vaccines that they have been contracted to make.

But I do think the bulk of J & J's vaccine to be made "domestically" (because the current doses are coming from the Netherlands) is probably going to be made by Merck as part of the arrangement that Pres. Biden brokered between Merck and J & J.

[twodogsbarking]

19. They forgot the micro chip.

Now they are saying it was Janssen & Janssen.

[Yavin4]

28. Some middle manager looking to make a name for him/her self by cutting QC steps and reduce costs.

The "do more with less" business cults need to sit this one out.

[inwiththenew]

29. There is immense pressure to get as many vaccines out and fast as possible

Mistake can happen in the rush to do this. Luckily they caught it.

[StarryNite]

32. At least it doesn't appear anybody was given the messed up vaccines.