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The mRNA vaccines from both Pfizer and Moderna contain cholesterol.

On the website for the UK National Health System NHS we may read:

The COVID-19 vaccines do not contain egg or animal products.

Another report indicates it contains no animal-derived cholesterol (but curiously notes that cow's milk was used in the manufacturing process):

Do Vaccines Contain Animal Ingredients?

The Pfizer, Moderna, and Janssen vaccines are free of animal-derived ingredients, in contrast to many other vaccines that include shark squalene, gelatin, cholesterol, egg, and milk. Pfizer has reported that its vaccine used a cow’s milk component in the manufacturing process, but the vaccine does not contain this ingredient.

— Physicians Committee for Responsible Medicine: "COVID-19 Vaccines: Safety and Efficacy", Good Science Digest, Mar 31, 2021

However, Magdeburg University are working on an alternative source of cholesterol. They firmly deny that the current crop of vaccines are vegan. They even claim they are potentially unsafe:

Vaccines based on mRNA […] are still based on animal cholesterol, which has several disadvantages.

For the industrial production of vaccines, the cholesterol is extracted from sheep's wool or animal tissue, for example. Here, however, there is a risk of triggering brain diseases through unintentional transmission - damage to the brain known as prion disease. A very well-known form in cattle since the 1990s is BSE.

A risk that could be eliminated in the future with the help of research from Magdeburg.

"Pflanzlich statt tierisch Uni Magdeburg macht RNA-Impfstoffe 'vegan' und sicherer", MDR, 31. May 2021. [Translated from German, LLC]

Closer to the source:

Chemists at Otto von Guericke University Magdeburg […] have succeeded for the first time in producing pharmaceutical cholesterol from plant-based raw materials using a highly effective process. In the future this will make it possible to make available large quantities of the molecule urgently needed for the production and administration of modern mRNA-based vaccines, […]

— Universität Magdeburg: "Gamechanger in der Impfstoffproduktion", Press Release, 25.05.2021. [Translated from German, LLC]

The general sources for injectable cholesterol are confirmed by one phospholipide manufacturer:

Source of cholesterol
The medicinal cholesterol CHO-HP is in great demand every year. However, because it is a multi-chiral substance and is difficult to synthesize, it is currently obtained by two methods: animal tissue extraction and lanolin extraction. […] However, with the emphasis on drug safety, cholesterol derived from lanolin will surely gradually replace cholesterol derived from animal organs.

"Introduction to the source and application of cholesterol", AVT, 2020-09-30.

All this gets even more complicated when looking at the list of prescribed/allowed ingredients as listed in the European Pharmacopeia (Ph. Eur.):

Cholesterol For Parenteral Use – Cholesterolum ad usum parenteralem C27H46O [57-88-5] Mr 386.7
Definition:
Cholest-5-en-3β-ol obtained from Wool fat (0134). [emphasis added, LLC]

— Council of Europe: "European Pharmacopoeia", 102019. (p 2202)

Let's focus on Pfizer/BionTech's Comirnaty/Tozinameran mRNA vaccine:

Composition
In addition to the mRNA molecule, the vaccine contains the following inactive ingredients (excipients):

ALC-0315, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), ALC-0159, 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol [emphasis added, LLC]

Comirnaty's package leaflet doesn't state the source of the cholesterol (which it normally has to do as well?).

It is clear that a requirement for prior animal testing poses a problem for strict vegans, for any vaccine.

Now it seems that there is also conflicting information out there for the actual ingredients used in manufacturing, and especially for the contents of the finished product:

  • whether 'some animal derived products were used during manufacturing but not contained in final product'
  • as well as 'some animal derived products are contained in the final product'
  • that the 'product is vegan', which would at least require of it to be free of animal derived products in the finished product
  • that the final product would by law be required to contain animal derived products, specifically cholesterol (As otherwise it would be not marketable at all, animal source being the only approved source, neither plant derived not fully synthetic sources allowed, even if structurally identical.)

Some say the final product is vegan, while some say the exact opposite.

Does Pfizer/BionTech's Comirnaty/Tozinameran mRNA vaccine contain in the final product animal-derived cholesterol, making it non-vegan?

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    Maybe it's the particular molecule they are using in the vaccine, but cholesterol total synthesis has existed since the 1950s. – rjzii Jun 21 at 22:43
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    Does "vegan" mean "does not contain stuff from animal origin" or "no stuff from animal origin was used for production" to you? – I'm with Monica Jun 22 at 7:58
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    “which it normally has to do as well?” — does it?! Source for that statement? — Furthermore, is there any approved medication that hasn't undergone animal safety testing? I thought that was usually part of regular approval (prior even to phase 1). I know that precursors of mRNA vaccines were tested in animals (contrary to false claims by vaccine denialists). – Konrad Rudolph Jun 22 at 8:17
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    @LangLаngС The point of my comment is that I’ve never heard this requirement and I see no reason to assume it to be true. So: what makes you think otherwise? — Yes, for new medication I would assume that at some point in its development animal (safety) testing will have been performed. Animal models are simply indispensable to much of modern biology. If this is incompatible with veganism then that’s very bad news for vegans (though obviously it shouldn’t be news to practitioners). – Konrad Rudolph Jun 22 at 10:13
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    I don't think there is a universally agreed upon definition of vegan, which may make this question hard to answer objectively. – gerrit Jun 22 at 13:20
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Does Pfizer/BioNTech's Comirnaty/Tozinameran mRNA vaccine contain anything derived from animals, specifically animal-derived cholesterol, making it non-vegan?

No. Neither the cholesterol nor any other ingredient is animal-derived.

The UK Department of Health and Social Care published a "Public Assessment Report" last updated on June 4, 2021. In this report, they describe the Pfizer/BioNTech vaccine's various ingredients, separating them into a section on the "active substance" (mRNA) and a section on the "excipients" (everything else in the vaccine). Excipients are "a constituent of a medicine other than the active substance," and include the lipids (and cholesterol) used in the vaccine. The report writes that

No excipients of animal or human origin are used in the finished product.

This leaves the mRNA. According to the same report, the mRNA is not derived from animals either. To produce the mRNA, DNA is mass manufactured in Escherichia coli, a bacterium. The DNA is then converted (or, in biology parlance, transcribed) to RNA in vitro (i.e. not in an animal).

Thus, no ingredients in the Pfizer vaccine are derived from animals.


For those interested, the ingredients in the Pfizer vaccine are "mRNA, lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose."


The above is a complete answer.

It remains nearly identical to my initial answer. Additional info to specifically address LangLangC's concerns:

LangLangC believes that the UK government statement that the Pfizer/BioNTech vaccine does not contain excipients of animal origin (quoted in my answer) contradicts with the European Pharmacopoeia and therefore contradicts with "the law." LangLangC believes that the vaccine must fully comply with the European Pharmacopoeia and, therefore, the cholesterol must be animal-derived. I don't believe there is a contradiction or that EU law requires fully complying with the European Pharmacopoeia.

The European Medicines Agency, which is responsible for regulating vaccines in the EU, has published an aptly-titled "Assessment report" on the Pfizer/BioNTech vaccine.

In this report, they devote a section to "Manufacture of the product and process controls." Here is the section on "Control of excipients."

ALC-0315 and ALC-0159 are novel excipients, not previously used in an approved finished product within EU. Additional information is provided separately in Section A.3 of the dossier.

DSPC is a non-compendial excipient sufficiently controlled by an in-house specification.

Cholesterol is sufficiently controlled according to the Ph. Eur. monograph with additional tests for residual solvents and microbial contamination.

The other excipients (sucrose, sodium chloride, potassium chloride, disodium phosphate dihydrate, potassium dihydrogen phosphate and water for injection) are controlled according to respective Ph. Eur. monograph.

The processing aids ethanol and citrate buffer are controlled according to Ph. Eur. standards and for HEPES and EDTA, reference is made to the active substance.

I find it very telling that every single excipient that is listed in the European Pharmacopoeia is described as "controlled according" to the pharmacopoeia except for cholesterol, which is "sufficiently controlled according" to the pharmacopoeia. This different phrasing for cholesterol allows for the cholesterol to not be animal-derived, in agreement with the UK government report.


I will now address other sources in LangLangC's question and LangLangC's answer:

Sources from LangLangC's question.

  • Article from the Physicians Committee for Responsible Medicine

    The Pfizer, Moderna, and Janssen vaccines are free of animal-derived ingredients, in contrast to many other vaccines that include shark squalene, gelatin, cholesterol, egg, and milk. Pfizer has reported that its vaccine used a cow’s milk component in the manufacturing process, but the vaccine does not contain this ingredient.

    I could not corroborate this statement with any other source. Searches of "cow" and "cow's milk" with "Pfizer" returned no relevant results. The linked source is a "dead link" and has not been archived. @Jack Aidley discusses this in an answer that I find insightful:

    "We have no information allowing us to be certain as to how, or why, cow's milk is being used by Pfizer but given what we do know I would suggest it is quite plausible that it is being used in quality control testing, although casein is also sometimes used in bacterial growth media I would be surprised if that was the case for E. coli."

    -- Read Jack Aidley's full answer here

  • Two German news sources on synthetic cholesterol mdr.de and University Magdeburg

    At the moment, most of the cholesterol required by industry comes from animal sources: either by extraction from fat from sheep's wool or from animal tissue. Through human and veterinary medical devices there is a risk of transmission of spongiform encephalopathy (TSE), an irreversible damage to the brain. -- University Magdeburg, translated from German

    As @laolux pointed out, this says most and not all of the cholesterol required by industry and not medicine specifically. Additionally, Sigma-Aldrich sells "synthetic cholesterol, animal component-free" so I completely doubt the University Magdeburg's press release that they are developing synthetic cholesterol for the very first time.

  • Quote from AVT (Shanghai) Pharmaceutical Technology Co., Ltd

    The medicinal cholesterol CHO-HP is in great demand every year. However, because it is a multi-chiral substance and is difficult to synthesize, it is currently obtained by two methods: animal tissue extraction and lanolin extraction. […] However, with the emphasis on drug safety, cholesterol derived from lanolin will surely gradually replace cholesterol derived from animal organs.

    This is irrelevant to the Pfizer/BioNTech vaccine specifically.

  • European Pharmacopoeia

    Reading monographs 0593, 0993, and 2397, which are relevant for cholesterol (and which I cannot access), might give me new insight. I currently have no comments here.

  • Ingredients list of Pfizer/BioNTech vaccine

    I agree the vaccine contains cholesterol.

Sources from LangLangC's answer.

  • EMA Assessment report on Moderna vaccine

    No comment.

  • Control of excipients (P.4)

    1. It should be confirmed that cholesterol will be controlled in line with Ph. Eur. monograph Cholesterol for parenteral use (2397) for future batches and not Ph. Eur. monograph Cholesterol (0993).

    I cannot access this source. Regardless, "it should be confirmed" does not mean it has been confirmed.

  • The manufacturer Evonik partnering with Pfizer/BioNTech

    Commercial lipid quantities are to be produced at Evonik's Hanau and Dossenheim sites in Germany as early as the second half of 2021 as part of a strategic partnership with BioNTech.

    […]

    Evonik already supplies one of the most important lipids for mRNA vaccines in pharmaceutical quality to multiple customers: A non-animal derived cholesterol under the brand name PhytoChol®.

    LangLangC seems to use this as a source for the fact that Pfizer/BioNTech isn't currently using manufactured cholesterol. I will cite an article from Vox.

    “Relatively small amounts of mRNA are enough to immunize a lot of people,” explained Pieter Cullis, a biochemistry professor who has been described as the “grandfather” of the lipid nanoparticle technology, and is the co-founder of the company Acuitas Therapeutics, whose tech has been licensed for the Pfizer/BioNTech vaccine. “The holdup seems to be more on the manufacturing of the other components like the ionizable cationic liquid and cholesterol, which are two of the larger components of the lipid nanoparticle.”

    The quote talks about a partnership between Acuitas Therapeutics, a different manufacturing company, and Pfizer. The article also talks about manufacturing cholesterol for the Pfizer/BioNTech vaccine.

  • Merck sources

    To meet the high demand for lipids, a key component of mRNA-based vaccines and therapeutics, Merck, a leading science and technology company, has launched a new, high-purity synthetic cholesterol product, nine months ahead of schedule. Merck press release

    Earlier on in the article, the press release includes "One of a few companies that produces lipids in quantities needed to meet demand for mRNA therapeutics, including Pfizer-BioNTech Covid-19 Vaccine." This does not say Merck is the only company producing lipids (such as cholesterol) for the Pfizer/BioNTech vaccine. It's entirely possible (even probable) other partners are involved.

  • EMA Assessment report on Pfizer/BioNTech vaccine

    The same report writes that "Cholesterol is sufficiently controlled according to the Ph. Eur. monograph" instead of just "Cholesterol is controlled," which was done for all other excipients included in the monograph. I find that difference telling as it allows wiggle room for the Pfizer/BioNTech vaccine to have used cholesterol that is not animal-derived, as the UK government report states.

    @Daniel Hatton found a document dated June 2021 that says:

    Cholesterol for parenteral use (2397)

    Definition: revised to allow the use of synthetic cholesterol; Test section indicates which tests apply depending on the source of the cholesterol used (derived from wool fat or synthetic).

    @LangLangC found another document that says the "implementation date" of the above edition supplement is January 1, 2022.

  • German law source

    I don't know how strictly this particular law is enforced. LangLangC also writes "How this apparent 'deficiency' that the EMA asked Moderna specifically to rectify — but both manufacturers seem to ignore by the second half of 2021 — might be compatible with for example the German law AMG $55,8: remains to be seen (and is probably out of scope here)."

All this said, I will be sending a few emails to better understand what exactly is going on with the incomplete compliance with the Ph. Eur.

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    This takes one statement and declares it 'truth'. Thus you emphasize one side of the two possibilities. However: the Magdeburg researcher as well as the requirements by EurPh are in contradiction to this statement (and the ultimate source of cholesterol in Comirnaty still not cleared up. Is it half- or fully synthesized then? Plant-sterol or de novo sourced? How do you resolve that contradiction? How do you weigh that (unreferenced) assertion in the report you cite against another expert and 'the law'? – LangLаngС Jun 21 at 23:23
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    @LangLangC I don't see a contradiction. The Magdeburg researcher says cholesterol used in vaccines commonly comes from animal sources. Pfizer says the cholesterol they use does not. – lambshaanxy Jun 22 at 6:57
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    "No excipients of animal or human origin are used in the finished product" could easily mean that they were used in the production process, but are not present in the finished product, anymore. Regarding the property "vegan" that is quite relevant! – I'm with Monica Jun 22 at 7:56
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    @I'mwithMonica - It COULD, if that phrase was all we had to go on, but then the answer goes through and details the processes, which shows that it does not. – PoloHoleSet Jun 22 at 13:37
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    @LangLаngС - The answers specifies, from the source, and also citing third party analysis. That's a lot more detailed and specific than the general statement you say contradicts it. – PoloHoleSet Jun 22 at 13:39
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The attribution in the question is incorrect. This quote from the article:

Vaccines based on mRNA […] are still based on animal cholesterol, which has several disadvantages.

For the industrial production of vaccines, the cholesterol is extracted from sheep's wool or animal tissue, for example. Here, however, there is a risk of triggering brain diseases through unintentional transmission - damage to the brain known as prion disease. A very well-known form in cattle since the 1990s is BSE.

is not attributed to Professor Dieter Schinzer of the University Magdeburg, nor to anyone else from the university. Tellingly, it switches to quotation for only this part, and for the main blockquote:

Dadurch "… können solche Verunreinigungen und Kontaminationen nicht auftreten", sagt Dieter Schinzer, Professor am Institut für Chemie der Universität Magdeburg.

that is:

As a result, "... such impurities and contamination cannot occur," says Dieter Schinzer, professor at the Institute for Chemistry at Magdeburg University.

There is no direction quotation, nor source, that supports the assertion regarding BSE. In fact, I am unable to find any evidence of any transmission of BSE (TSE, more precisely) to humans from extracted Cholesterol. In fact, rather than being claims made by Magdeburg university, these seem to be claims made by an unnamed writer for mdr.de.

Meanwhile, non-animal origin is freely available for purchase by any laboratory. Given this, there seems no reason to cast doubt on Pfizer's claims regarding the ingredients of their product.


Regarding a side point, rather than being curious, the use of cow's milk is common in molecular biology laboratories, typically in the form of dried milk powder or casein-powder. This is used as a blocking agent in many procedures, but particularly in northern blotting (used to detect RNA) and Southern blotting (used to detect proteins). We have no information allowing us to be certain as to how, or why, cow's milk is being used by Pfizer but given what we do know I would suggest it is quite plausible that it is being used in quality control testing, although casein is also sometimes used in bacterial growth media I would be surprised if that was the case for E. coli.

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  • "BSE" is not the main point here, but the Magdeburg PR states: "Currently, the main quantities of industrially required cholesterol come from animal sources: either by extraction from fat from sheep's wool or from animal tissue. Via human and veterinary medical products, this poses a risk of transmitting spongiform encephalopathy (TSE), an irreversible damage to the brain. "Such impurities and contaminations cannot occur in the production of cholesterol from plant-based raw materials," says Schinzer." Main point is: how are non-animal/PhEur assertions compatible. What's in, how approved? – LangLаngС Jun 22 at 17:52
  • Whether there is any risk for TSE or not, in whatever, if animal-derived (I don't claim "Magdeburg is right", just "they claim it in connection with this"): ispe.org/pharmaceutical-engineering/march-april-2018/… doi.org/10.1002/ejlt.201400219 Even EMA attests for Moderna (link in my A): "All materials conform with Certificates of Analysis (CoAs) or Certificates of Compliance, which includes verification of bovine spongiform encephalopathy/transmissible spongiform encephalopathy (BSE/TSE) certificates, as required." – LangLаngС Jun 22 at 18:08
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    The claim about TSE is relevant to the credibility of the source (mbr not Magdeburg Universität). The claim that most Cholesterol is animal sourced is completely irrelevant to whether the cholesterol in this vaccine is. – Jack Aidley Jun 22 at 20:16
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    Most cholesterol in industrial use is not the same as most cholesterol in medical use. Medical use of cholesterol could be very tiny compared to other industrial use. – laolux Jun 23 at 1:39
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    @LangLаngС yes, crucial word indeed. It serves as a warning. "Using regular industrial material in medical products is dangerous, because ...". Just like using "industrial grade" silicone in medical products such as silicone implants is dangerous, as a French company well knows. The press release still makes no claim that most medically used cholesterol is animal sourced. Your other sources might (I am not an expert on this), but the press release does not and actually chose careful wording to avoid such claim. – laolux Jun 24 at 1:24
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It is clear that a requirement for prior animal testing poses a problem for strict vegans, for any vaccine. (...) Does Pfizer/BionTech's Comirnaty/Tozinameran mRNA vaccine contain in the final product animal-derived cholesterol, making it non-vegan?

I think the premise of this question is somewhat incorrect.

Even if a product contains animal-derived ingredients or was animal-tested, vegans will not always have a problem with that (and in that sense, calling it non-vegan would not make much sense if vegans would still use it).

I will start with the definition of veganism by The Vegan Society which is considered canon by many vegans:

"Veganism is a philosophy and way of living which seeks to exclude—as far as is possible and practicable—all forms of exploitation of, and cruelty to, animals for food, clothing or any other purpose; and by extension, promotes the development and use of animal-free alternatives for the benefit of animals, humans and the environment. In dietary terms it denotes the practice of dispensing with all products derived wholly or partly from animals."

I've highlighted the relevant part in bold.

To the best of my knowledge, all of the popular vaccines the majority of people have access to were made with animal-derived ingredients and/or were animal tested. At the same time, the scientific evidence suggests that not vaccinating ourselves we will inflict great harm to ourselves and others, and indirectly contribute to the death toll and the increased demand for other animal-based or tested drugs for treating people with COVID-19 by spreading the pandemic further.

Thus, avoiding a shot with a vaccine containing animal-derived or tested products is not "practicable" or, in the case of some countries with mandatory COVID-19 vaccination, e.g. some regions of Russia, even possible.

(By extension, this logic applies to other animal-derived and tested drugs.)

The Vegan Society provides a good summary why it's wrong to apply the "vegan"/"non-vegan" labeling to COVID-19 vaccines in the current situation: https://www.vegansociety.com/news/news/vegan-society-response-covid-19-vaccine

And here is another link on whether a vegan person should avoid taking prescription drugs that taps into the same logic:

The Vegan Society - Medications

(Full disclosure: I'm vegan, me and most of my vegan friends have either taken COVID-19 shots or are planning to do so in the near future. And while this is a very interesting question and discussion, I doubt most anti-vax vegans refuse to vaccinate for this reason alone.)

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  • The 'premise' isn't just 'avoid or not'. The premise is: 'is it this or that', as no clear evidence for either is available, despite multiple sources giving assertions, seemingly in contradiction, firmly claiming or strongly implying one thing and the other. All the while leaving for EMA jurisdiction the problem that the end product in principle would be required to contain animal based substances, unless exception was argued for and granted. But the latter being nowhere to be read in publications to settle this so far. "Why it's wrong to…" is a philosophical/political prescription. – LangLаngС Jun 24 at 1:37
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    @LangLаngС That's certainly an interesting question. But if you are only interested in whether or not animal-derived ingredients are a sine qua non for a vaccine, you should avoid using the word "vegan" to avoid confusion. Veganism is inherently philosophical and political. If you buy instant beef noodles and throw away the sachet with beef broth, the noodles are not going to become vegan despite not having any animal ingredients in them. – undercat Jun 24 at 2:11
  • Well, that would shift the goal posts? The interest is firmly not on 'should one do or don't, tell us what to do'. The interest is on accurate & honest info on the ingredients. With that info present anyone, incl vegans of various strains, strictness & adherence can make up their own minds. – LangLаngС Jun 24 at 9:01
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    Yes, historically, the Vegan Society in the UK has taken the position that it's OK to take vaccines that contain squalene oil, gelatine, (battery?) egg etc., because of the "as far as is possible and practical" qualification. However, (subject to a final answer to this question) Pfizer, AstraZeneca, and Moderna have now shown that it is possible and practical to make an animal-ingredient-free vaccine for a virus with spike proteins; that may change some vegans' calculus for some pre-existing vaccines going forward. – Daniel Hatton Jun 24 at 10:45
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Status: unresolved

Preliminary summary:

Neither Pfizer nor Moderna make that information publicly available. Inquiries were so far unsuccessful. Some authority sources claim that the finished product would not contain anything animal derived. Some authority sources continue to claim that the products do contain animal sourced cholesterol. Neither side provides definitive evidence for their versions.

But within the area where the European Medicines Agency (EMA) regulations apply, the products would strictly have to contain cholesterol sourced from sheep's wool fat according to the definition set forth in monograph 2397 of the European Pharmacopeia (Ph.Eur.).

Exceptions to that rule — that is about to change to also include synthetic sources starting in 2022 — are possible but have to be granted. That information on whether an exception was granted or not is also not publicly available.

Publicly available info suggests that from the second half of 2021 at least a large part of cholesterol produced for the products will come from synthetic sources.

Initially both companies were told by the EMA to adhere to monograph 2397 standards and use cholesterol from wool fat.

That leaves a lot of direct and circumstantial evidence to point towards the current possibilities:

  1. Both companies currently adhere to monograph 2397, and indeed use animal sourced cholesterol in the finished product.

  2. The companies may have gotten explicit approval to use non-compendial cholesterol, but this exception to the rules is not made public so far.

  3. The companies did not get the explicit approval to deviate from the current Ph.Eur. standards, but use plant-based or synthetic cholesterol anyway. This seems not impossible but rather unlikely, as that would mean that the products would currently be not marketable at all.

The above applies to the area of mainly Europe under jurisdiction of the EMA. Inferences about other regions were the products are marketed as well are not possible and await further clarification, as again: neither Pfizer nor Moderna disclosed this information.

Personal evaluation:


Evidence gathered:

The European Medicine Agency (EMA) published two assessment reports, one for Moderna and Pfizer.

For Moderna, it indeed states it indeed contained a non-animal derived cholesterol at the time of the assessment and that it would be therefore in violation of the European standards as codified in the European Pharmacopeia (Ph.Eur.):

Concerning the use of non-Ph. Eur. grade cholesterol also cited by the company applicant a request to only used Ph. Eur. cholesterol has been requested (REC)). […] (EMA/15689/2021 Page 22/169)

c) Cholesterol is stated to be non-compendial and compendial “Synthetic Cholesterol (Phytochol)”, whereas compendial is not further defined. In the Ph. Eur two monographs are provided for cholesterol, monograph 0993 and monograph 2397.

For parenteral use cholesterol has to be in compliance to monograph 2397. [emphasis added, LLC]

The applicant is advised to solely use cholesterol of this quality and to update the provided specification and related documentation accordingly, to use non-compendial cholesterol has to be sufficiently justified.

  1. P.4 Control of Excipients a) The applicant should provide evidence that the impurities and/or degradation products resulting from PEG2000-DMG, cholesterol and DSPC have been sufficiently investigated and do not result in the formation of lipid-RNA species by 31-01-2021.

  2. P.5 Control of finished product The applicant provide evidence to confirm that the impurities and/or degradation products resulting from PEG2000-DMG, cholesterol and DSPC have been sufficiently investigated and do not result in the formation of lipid-RNA species by 31-01-2021.

— 11 March 2021 / EMA/15689/2021 Corr.1*1 / Committee for Medicinal Products for Human Use (CHMP) COVID-19 Vaccine Moderna Common name: COVID-19 mRNA Vaccine (nucleoside-modified) Procedure No. EMEA/H/C/005791/0000 Assessment report EMA/15689/2021 Page 162/169 (PDF)

A similar concern was issued for Pfizer as of 30. November 2020 for their application of approval:

Control of excipients (P.4)
10. It should be confirmed that cholesterol will be controlled in line with Ph. Eur. monograph Cholesterol for parenteral use (2397) for future batches and not Ph. Eur. monograph Cholesterol (0993).

Amsterdam, 30 November 2020 EMA/CHMP/641856/2020EMA/CHMP/641856/2020 Committee for Medicinal Products for Human Use (CHMP) (link)

The substance "Phytocol® Puriss" was developed by Wilshire Technologies in the USA and is marketed through Evonik. Concluding from ads it seems to be available at least since 2016. Price seems to be 50 g for $8,410.00.

The manufacturer Evonik is now also partnered with BionTech the developer of the Pfizer product:

Commercial lipid quantities are to be produced at Evonik's Hanau and Dossenheim sites in Germany as early as the second half of 2021 as part of a strategic partnership with BioNTech.

[…]

Evonik already supplies one of the most important lipids for mRNA vaccines in pharmaceutical quality to multiple customers: A non-animal derived cholesterol under the brand name PhytoChol®.

— By Dan Hutchins : "Evonik partners with BioNTech to manufacture lipids for COVID-19 vaccine", News-Medical.Net, Mar 2 2021. [Emphasis added, LLC]

Similar data is derived from newspaper reports about previous suppliers of lipids like cholesterol for Pfizer: Merck and Acuitas (Feb 2021).

Interestingly, Merck seems to supply both: animal cholesterol (variant 1: C₂₇H₄₆O 5g/EUR 68,40; variant 2, explicitly from wool fat: C₂₇H₄₆O 1kg/EUR 1.730,00) and synthetic cholesterol SyntheChol®, C₂₇H₄₆O, price on request.

While the company indeed claims for all variants that they would meet Eur.Ph. standards for quality, they do not disclose how the synthetic variant would be able to comply to the most applicable regulation monograph 2397. The simple listing of "Ph.Eur." is therefore only in compliance with monograph 0993, and thus not for injectable use per se.

Merck did state very recently, that they are new to this, since February 2021, and now getting ready:

To meet the high demand for lipids, a key component of mRNA-based vaccines and therapeutics, Merck, a leading science and technology company, has launched a new, high-purity synthetic cholesterol product, nine months ahead of schedule.

—Merck: "Merck Accelerates Scale Up of Lipids to Meet Covid-19 Demand", Press Release, Darmstadt, Germany, 26 May 2021

The other partner Acuitas seems to be focussed on the Lipid-Nano-Particles other than cholesterol.

Initially, the Pfizer product was assessed by the EMA on conditional marketing approval as:

All excipients except the functional lipids ALC-0315 and ALC-0159 and the structural lipid DSPC comply with Ph. Eur. The functional lipid excipients ALC-0315 and ALC-0159, are classified as novel excipients. Both structural lipids DSPC and cholesterol are used in several already approved finished products.

— 19 February 2021 EMA/707383/2020 Corr.1*1 Committee for Medicinal Products for Human Use (CHMP) Assessment report Comirnaty Common name: COVID-19 mRNA vaccine (nucleoside-modified) Procedure No. EMEA/H/C/005735/0000 EMA/707383/2020 Page 23/140 (PDF) [emphasis added, LLC]

While seemingly in conflict with the communication commentary upon application as of November 30 2020, (which lists 'what EMA thinks important), the EMA approval document confirms compliance with the compendium Ph.Eur., indicating the EMA thinks it complies with monongraph 2397, making the cholesterol animal sourced — per definitionem.

That means that the Moderna product might be vegan in the sense of at least 'does not contain animal derived cholesterol' in the finished product. Although this then is in violation of the current version of European Pharmacopoeia (Ph. Eur.) 10th Edition.

How this apparent 'deficiency' that the EMA asked Moderna specifically to rectify — but both manufacturers seem to ignore by the second half of 2021 — might be compatible with for example the German law AMG $55,8: remains to be seen (and is probably out of scope here):

In the manufacture of medicinal products, only substances […] may be used […] which comply with the recognised pharmaceutical rules.

With "comply with the recognised pharmaceutical rules" meaning in accordance to the 'Good Manufacturing Practice' (GMP) as formulated in the German Pharmocopeia DAB (Deutsches Arzneibuch) and the European one, Eur.Ph.

Pfizer/BionTech brought a product to market that did and apparently does contain animal derived cholesterol, as assessed by the EMA. Meaning that it is/was in compliance with Ph. Eur. and uses animal derived cholesterol — but Pfizer plans to change that in the second half of 2021, switching to the plant-derived versions of the substance that is used by Moderna as well. If it contains animal derived cholesterol it is surely 'not vegan' at the moment.

Parenteral cholesterol as used by other vaccines would be Mosquirix or Shingrix. For Mosquirix the EMA found the following:

The applicant adequately justified the use of cholesterol that is compliant to Ph. Eur monograph Cholesterol <993>, instead of the monograph Cholesterol for Parenteral Use <2397> and will develop an endotoxin test for cholesterol raw material testing.

— 23 July 2015 EMA/CHMP/439337/2015 Committee for Medicinal Products for Human Use (CHMP) Assessment report MosquirixTM International non-proprietary name: Plasmodium falciparum and hepatitis B vaccine (recombinant, adjuvanted) Procedure No. EMEA/H/W/002300/0000 page 26/175 (PDF)

Which means that the EMA found the reasons presented to them for not using sheep's wool as a source and thus violating 2397 satisfactory. As long as the alternative source in compliance with 0993 would be monitored closely for "endotoxins". Note the date of cost-effective alternative source availability for non-animal cholesterol and the need for monitoring endotoxins closely. This is apparently still exclusively animal sourced but just not from wool fat.

Such explicit assessment and a given OK are still absent from any publicly available material I could find. Pfizer and Moderna were asked to provide either compliant products or justify not doing so. It seems they have not done so, as at least EMA has not published documentation for the manufacturers doing that to EMA's satisfaction.

Unless further information comes forward on this, we have to regard the claims made by the UK NHS and the Vegetarian society, both relying on information from Pfizer as dubious: according to EMA assessment, Pfizer's product was conditionally approved for the EU market with, and currently does contain, animal derived cholesterol.

The exact ingredients used are not fully publicly disclosed by the manufacturer.

As of November 2020 (PDF) — and in parallel to the requests to the manufacturers to adhere to monograph 2397 — there was discussion within the EMA to amend Ph.Eur..

The newest supplement 10.6, agreed upon in November 2020, published in May 2021, and to be implemented in 2022

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Monograph 2397 will allow the use of either wool fat or synthetic cholesterol:

Status In use Monograph Number 02397 English Name Cholesterol for parenteral use Pharmeuropa 32.2 Published in English Supplement 10.6

As detailed in the history of revisions here:

SUPPLEMENT 10.6 Definition: revised to allow the use of synthetic cholesterol; Test section indicates which tests apply depending on the source of the cholesterol used (derived from wool fat or synthetic). Identification: section updated. Related substances: test introduced for synthetic cholesterol. Bacterial endotoxins: test deleted as covered by the general monograph Parenteral preparations (0520).

Which means that with the start of 2022, both manufacturers do no longer need to use strictly wool fat derived cholesterol, or present an accepted reason for using non-compendial cholesterol, as then synthetic cholesterol will be compendial as well.

An explanation for the demonstrated need to watch out for the given risk of transmissible spongiform encephalitis (TSE) in the University of Magdeburg press release when employing animal derived cholesterol and the historic genesis of monograph 2397 requiring wool fat as the only compendial source not in need for exceptions when intended for parenteral use: these were meant as an explicit security measure to avoid any risk of TSE, as detailed also in chapter "5.2.8. Minimising the risk of transmitting TSE via medicinal products" especially section "6-7. Wool Derivatives" in Ph.Eur. 10.0. (p670 printed version).

The quality, source and status of both products now remains to to be ascertained by official sources.

A Freedom of Information request for transparency on this matter to the EMA from January 2020 is blocked and delayed to this day. (Publicly visible in English and German language at — FragDenStaat: Antrag nach EU-Verordnungen 1049/2001 sowie 1367/2006: "Impfstoffe [#210033]" Datum: 28. Januar 2021 / Deadline: 18. Februar 2021, last exchange listed as of June 15, 2021.)

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    Why are you complicating your already long answer with all this stuff about compliance, which is irrelevant to your original question? Also, despite all the verbiage you've expended here, I'm still not seeing a "smoking gun" proving that Pfizer is using animal-derived (lanolin) cholesterol. – lambshaanxy Jun 22 at 15:27
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    This answer would benefit from a massive simplification. The acronyms aren't made clear, the block quotes aren't provided with enough context, and the takeaways are buried in the text. It's extremely hard to understand. – jdf Jun 22 at 15:30
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    @lambshaanxy Simple: because it is complicated. EMA says Pfizer did comply. If it did comply, it contained animal derived cholesterol. Thus the simplistic NHS assertion must be quite false. Moderna didn't comply. Pfizer obviously either didn't as well (EMA simply trusting Pfizer, which didn't tell the truth to EMA, but to NHS?) or at least plans to go non-animal now. From 2nd half '21 both will not comply to either Ph.Eur. or AMG and go vegan—that is, unless they were vegan all along and thus Pfizer did never comply. Or there comes an explanation, official, that clears this conundrum. – LangLаngС Jun 22 at 15:37
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    @jdf I added more spelling out of the most relevant acronyms earlier. Please re-check which you seem essential for comprehension yet still missing. // But: Do you realize the impossible goals you set forth? Demanding simplification + shorter, yet more, especially context? If I give you more context (which will also be available at the links I provided), will you then complain that the criterion shortness got even worse? – LangLаngС Jun 22 at 21:48

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