Abschätzung zur europäischen Produktion des Oxford/Astrazeneca-Impfstoffs Vaxzevria/AZD1222

(Für Referenzen siehe nachfolgende Beiträge.)

Produktionsparameter

• Angestrebte Ausbeute: 5000 Dosen/L (a),(l)
• Angenommene Produktionslaufzeit: 1 Monat (a) (Herstellung des Wirkstoffs), unbekannt (Abfüllung, Qualitätskontrolle)

Kapazitäten

Liefermenge

• EU:
  • 11.4 M Dosen bis Anfang März (r)
  • 8.3 M Dosen im März (r)
  • ca. 10 M Dosen auf Lager für Ende März, so wie ca. 6 M Dosen im April (o)
• UK:
  • mindestens 11.7 M Dosen von Anfang Januar bis Anfang März (n)
  • davon etwas über 1 M EU-Import aus der Halix-Produktion (f),(p) Beginn der Impfung 4. Januar (h)

Leistung und Umfang

Halix: Da die erste Lieferung an das UK über 1 M Dosen aus der Halix-Produktion war (f),(p) würde bei einer Ausbeute von 5000 Dosen/L dazu der 250 L-Bioreaktor, der mit einem Produktionslauf 1.25 M Dosen erzeugen kann, passen. (q) Möglich wären allerdings auch mehrere Läufe des 100 L-Bioreaktor. (q) Die Leistung von 5-6 M Dosen pro Monat wird dagegen, vermutlich erst 2021 erreicht. (m)

Oxford Biomedica: 4 Millionen Dosen sollten 2020 kommen (d), stattdessen kam die erste Lieferung Anfang Januar 2021 aus der EU (f) und Lieferungen aus der UK-Produktion begannen wohl erst in Kalenderwoche 3. (g),(i) Das Ziel war 2 M Dosen pro Woche, was auf eine Monatsproduktion von 8 M Dosen pro Monat hindeutet.

Thermo Fisher/Senrise IV: Die Aussage dazu ist 4 M Dosen pro Monat vor, 8 M Dosen pro Monat ab Januar 2021. (k)

Zusammengefasst:

Schließlich die Abschätzung, woher der ausgelieferte Impfstoff kommt und in welchem Zeitraum er produziert wurde.

UK: 11.7 M bis Anfang März 2021

~ 9M, Differenz von ~ 3 M, möglicherweise höhere Ausbeute oder Beitrag von Cobra Biologics.

EU: 36 M bis in den April 2021

Wenn Senrise IV 2020 nur 4 M Dosen pro Monat produzieren konnte, kann diese Menge nicht allein dort hergestellt worden sein. Eine weitere Steigerung der Produktionsleistung auf 5000 Dosen/L ist wahrscheinlich.

Möglichkeit 1 (Lieferung aus der Produktion von Halix vor der offiziellen Zulassung durch die EMA):

33 M, Differenz ~ 3 M (Lieferungen 15. und 23. März), kann vielleicht in Produktionen verteilt werden

Möglichkeit 2 (ohne Halix-Produktion vor der EMA-Zulassung):

33 M, gleiche Differenz wie oben.

(a) 2020-05-12

https://www.bioindustry.org/up…4745-b0947da8d2834e60.pdf

Zitat

1 million doses should potentially be generated per 200L run. Across the Oxford consortium there is the potential for six such runs per month from mid-2020; total of 6 million doses per month.

Zusammenfassung/Deutung:

• Ausbeute: 5000 Dosen / L
• Zeit für einen Produktionslauf: 1 Monat

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(b) 2020-10-06

https://www.oxb.com/news-media…manufacturing-suite-oxbox

Zitat

Oxford Biomedica [...] announced today that the UK Medicines & Healthcare products Regulatory Agency (MHRA) has issued a Certificate of GMP compliance for the fourth GMP manufacturing suite within the Group's new Oxbox manufacturing facility.

Zitat

Both this suite and the suite approved in September will be operating at 1000L scale and at present will be dedicated to the manufacture of a COVID-19 viral vector vaccine candidate. Equipment for these two suites [...]

Zusammenfassung/Deutung:

• 2 x 2000 L Bioreaktoren für die Produktion von Vaxzevria/AZD1222 bei Oxford Biomedica (Oxford, UK) im Oktober
• 4 Vektor-Produktionseinheiten insgesamt

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(c) 2020-10-16

https://www.novasep.com/media/…ors-faqs-october-2020.pdf

Zitat

Q24: Does Novasep manufacture commercial viral vectors?

Yes, Novasep has 2 state-of-the-art commercial facilities on its Seneffe site: Senrise-IV is a multi-USP/DSP clean room facility with two independent manufacturing lines allowing to produce Drug Substances up to the USP scale of 2,000L.

Zitat

Our Seneffe site is the largest site of Novasep in Belgium. It hosts the large-scale clinical facility which allows to operate SUB bioreactors up to 1,000L.

Zusammenfassung/Deutung:

• 2 x 1000 L Bioreaktoren Gesamtkapazität von Senrise IV (Seneffe, Belgien)

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(d) 2020-11-04

Zitat

The timetable for delivery of the Oxford University/AstraZeneca COVID-19 vaccine candidate has slipped, the UK’s vaccine chief said, adding Britain will receive just 4 million doses of the shot this year.

Zusammenfassung/Deutung:

• nur 4 M Dosen Vaxzevria/AZD1222 können dem UK 2020 geliefert werden

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(e) 2020-12-08

https://www.halix.nl/2020/12/0…facture-covid-19-vaccine/

Zitat

HALIX B.V. signed an agreement with AstraZeneca AB for large-scale commercial drug substance manufacture of AZD1222, the adenovirus vector-based COVID-19 vaccine.

Under the agreement, HALIX will provide commercial manufacturing of drug substance at its state-of-the-art cGMP facility at the Leiden Bio Science Park in the Netherlands. To meet the increased demand, HALIX expands with two additional viral vector production lines.

Zusammenfassung/Deutung:

• Halix (Leiden, Niederlande) nutzt im Dezember 2020 eine Produktionseinheit für Vaxzevria/AZD1222 und plant um zwei weitere zu expandieren

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(f) 2020-12-08

https://www.reuters.com/articl…-astrazenec-idUSKBN28I1NH

Zitat

The "vast, vast, vast majority" - over 80% - of the 100 million doses AstraZeneca will produce for the United Kingdom will be made there, Ian McCubbin, manufacturing lead for the Vaccine Taskforce, said, but this year's first batches will not.

"The initial supply and it's a little bit of a quirk of the programme actually comes from the Netherlands and Germany," he told reporters.

Zusammenfassung/Deutung:

• die erste Lieferung von Vaxzevria/AZD1222 kommt von Halix (Leiden, Niederlande)

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(g) 2021-01-01

https://www.reuters.com/articl…-astrazenec-idUSKBN2962NT

Zitat

About two million doses of COVID-19 vaccine developed by Oxford University and AstraZeneca are set to be supplied every week by the middle of January in the United Kingdom, The Times reported.

AstraZeneca expects to supply two million doses of the vaccine in total by next week, the newspaper reported, citing an unnamed member of the Oxford-AstraZeneca team. "The plan is then to build it up fairly rapidly - by the third week of January we should get to two million a week," the report added.

Zusammenfassung/Deutung:

• UK-Produktion 2 M Dosen / Woche ab Kalenderwoche 3

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(h) 2021-01-04

https://www.bbc.com/news/uk-55525542

Zitat

[...] the first person to receive the Oxford-AstraZeneca Covid-19 vaccine.

Zusammenfassung/Deutung:

• Beginn der Impfung mit Vaxzevria/AZD1222

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(i) 2021-01-13

https://www.independent.co.uk/…astrazeneca-b1786684.html

Zitat

AstraZeneca will "imminently" scale up production to release 2 million doses of its vaccine each week in the UK, the firm’s chief executive has said.

Tom Keith-Roach, the president of AstraZeneca UK, said the company may be able to go above that figure from April onwards.

He said 1.1 million doses of the company’s Covid-19 jab, which was developed with Oxford University, have been released to the UK so far, but the aim was to reach 2 million doses per week on or before the middle of February.

Zusammenfassung/Deutung:

• 1.1 M Dosen Vaxzevria/AZD1222 an UK ausgeliefert
• Ziel von 2 M Dosen / Woche
• erst ab April steigerbar

(j) 2021-01-18

https://www.oxb.com/news-media…-opens-oxford-biomedica-s

Zitat

Prime Minister Boris Johnson formally opens Oxford Biomedica’s manufacturing facility Oxbox

Zitat

By October 2020, the Group had four manufacturing suites approved by the MHRA, three of which were contracted by AstraZeneca and are currently producing bulk vaccine at 1000L scale.

Zusammenfassung/Deutung:

• 3 der 4 Einheiten von Oxford Biomedica (Oxford, UK) werden für die Produktion von Vaxzevria/AZD1222 verwendet

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(k) 2021-02-12

https://www.politico.eu/articl…rus-vaccine-supply-chain/

Zitat

But Thermo Fisher this week said it had done what it was obliged to under its contract with the drugmaker. "We have complied with all the contractual requirements we have with AstraZeneca," Cedric Volanti, Thermo Fisher’s vice president for EU told a press conference Wednesday.

Zitat

A successful strategy "has to have multiple sites," one EU official said. "It appears now the U.K. is holding onto their plants, [and AstraZeneca was] relying solely on Thermo Fisher Scientific to manufacture for everybody - it's impossible."

The official, who wished to remain anonymous, said that while the plant's production was running thousands of doses behind, inspections had revealed no serious issues that would leave it millions of doses off target. The Belgian factory was "a bit behind schedule" but it was "never their intention to cover the whole of the EU drug substance manufacturing - it's unfeasible," the official said.

Zitat

When the Belgian plant - previously owned by Novasep - began producing the drug substance for AstraZeneca's vaccine in 2020, its dose production volumes were roughly 4 million doses per month, according to the EU official. That rose to 8 million a month in January following an expansion.

Zusammenfassung/Deutung:

• 4 M Dosen / Monat von Senrise IV (Seneffe, Belgien) in 2020
• 8 M Dosen / Monat ab Januar 2021

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(l) 2021-02-25, Befragung im EU-Parlament

https://multimedia.europarl.eu…cal-industry-_I202519-V_v

Zitat

[Pascal Soriot, Chief Executive Officer, AstraZeneca]

And so this question of yield has impacted our ability to deliver the volume we were looking for, for the EU. I can tell you though that the overwhelming majority of what is manufactured in the EU, including the Netherland facility is actually going to EU supply.

Zitat

And indeed there was an agreement, were several agreements signed by the UK government with manufacturers. One is in the Netherlands, one is in the UK and we are actually sharing because essentially the Netherland manufacturer was reserved originally by the UK and in fact that manufacturer is supplying Europe today.

Zitat

The yield is actually the number of doses of vaccine that you extract out of one litre in your bioreactor. We have bioreactors that have 1000 litres and 2000 litres and depending on how many doses of vaccine you get per litre than of course it influences the number of vaccines you can produce. And the yield varies from a factor of 1 to 2 between sites.

Zitat

But I think it's important to understand, when we entered this agreement with Oxford University the assumption that the University was using, was a yield of 5000, which is - which means 5000 doses of vaccine coming out of one litre. [...] it turns out that some of the sites have delivered this assumption and some other sites have delivered half of the assumption. And therefore if you deliver half of the assumption which is half of the number of doses per litre your production is half of what you expected. So it's pretty simple. It's just the simple math if you have a lower yield, a lower number of vaccines per litre, than you produce less. If we had reached the assumed yield we would be absolutely on track with our supply.

Zusammenfassung/Deutung:

• Halix hat UK versorgt, soll aber nun die EU mitversorgen
• Theoretische Ausbeute: 5000 Dosen / L
• Ausbeute ist bei einigen Produktionsstätten um den Faktor 2 verringert

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(m) 2021-03-03

https://www.politico.eu/articl…after-eu-export-controls/

Zitat

In January, the Commission introduced new export controls requiring companies to get authorization from national authorities to export vaccines outside the bloc.

Since then, "everything has stayed in the EU," Breton said, adding that AstraZeneca hasn't requested to send vaccines abroad since the authorization scheme.

Zitat

Breton made those comments in The Hague after visiting the drugmaker's Dutch Halix site to make sure companies "deliver what is promised." He said he was "impressed" with the yield from the Dutch producer, which can make between 5 million and 6 million doses a month, with "a significant part" for the EU.

Zusammenfassung/Deutung:

• Halix kann 5-6 M Dosen pro Monat produzieren
• kein Impfstoff von Astrazeneca wurde aus der EU exportiert

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(n) 2021-03-07

https://assets.publishing.serv…rd_reporting_07.03.21.pdf

Zitat

As of 07 March, an estimated 10.9 million first doses of the Pfizer/BioNTech vaccine and 11.7 million doses of the Oxford University/AstraZeneca vaccine, had been administered, and around one million second doses, mostly the Pfizer/BioNTech vaccine, had been administered.

Zitat

Table 1: First Dose 22377255 (19015497 + 998296 + 588803 + 1774659)

Table 2: Second Dose 1142650 (797321 + 183739 + 42851 + 118739)

Zusammenfassung/Deutung:

• bis Anfang März sind mindestens 11.7 M Dosen Vaxzevria/AZD1222 an das UK geliefert worden

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(o) 2021-03-24

https://www.francetvinfo.fr/sa…es-en-italie_4345847.html

Zitat

There are no exports currently planned, other than to COVAX countries. There are 13m doses of vaccine waiting for quality control release to be dispatched to COVAX as part of our commitment to supply millions of doses to low income countries. The vaccine was made outside the EU and brought to the Anagni plant to be filled into vials. The EU fully supports supplying low and middle income countries through the COVAX facility.

There are another 16m doses waiting for quality control release to be dispatched to Europe. Close to 10m doses will be delivered to EU countries during the last week of March, the balance in April as the doses are approved for release after quality control.

Zusammenfassung/Deutung:

• 16 M Dosen lagern in bei Catalent in Anagni, ca. 10 M Dosen Lieferung für die unmittelbare Lieferung an die EU und ca. 6 M Dosen für Lieferung im April nach "quality control"

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(p) 2021-03-25

https://www.bloomberg.com/news…estrictions-summit-update

Zitat

The EU has exported 21 million vaccine doses to the U.K., a European Commission official said, on condition of anonymity. Of those shots, just over a million were produced by AstraZeneca Plc., the official added. The previously undisclosed figures include shipments sent before an export-authorization mechanism was introduced at the end of January.

Zusammenfassung/Deutung:

• die EU hat etwas mehr als eine Million Dosen Vaxzevria/AZD1222 an das UK exportiert

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(q)

https://www.halix.nl/production-capacity/

Zitat

"[...] with a BSL2 single-use bioreactor capacity of up to 250 L and a BSL3 single-use bioreactor capacity of 100 L."

"Up to 250 L single-use bioreactor for virus production (BSL2)"

"Up to 100 L single-use bioreactors for virus production (BSL3)"

"Up to 1,000 L single-use bioreactor for protein production (BSL2)"

Alles anzeigen

Zusammenfassung/Deutung:

• Halix (Leiden, Niederlande) hat drei Bioreaktoren, von denen zwei für die Vektorproduktion vorgesehen sind

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(r)

https://impfdashboard.de/stati…iveries_timeseries_v2.tsv

19.7 M Dosen für die EU nach dem Bevölkerungsschlüssel aus den Lieferungen an Deutschland zurück geschlossen

Dieser Artikel schreibt auch der Produktion in Maryland, USA eine gewisse Rolle in der Versorgung der EU zu:

https://www.politico.eu/articl…roduction-woes-documents/

Das würde die Abschätzungen natürlich ändern, aber ich steige da nicht wieder ein.

Ergänzung:

https://apnews.com/8e4bac19a9175cb71e5fc4f36ea82f62