Another key point is that batches of this rushed experimental substance differ significantly
(translation of the German original, see below)
Five professors want to know more details about the Covid 19 ‘vaccine’ from BioNTech. The company’s initial answers raise new questions.
Four chemistry professors posed questions to BioNTech. But for the scientists, who have since been joined by a fifth colleague, Prof. Dr. Tobias Unruh, Physics of Condensed Matter, Friedrich-Alexander University of Erlangen-Nuremberg, BioNTech’s answers raise new questions. The Berliner Zeitung documents the professors’ follow-up questions in the following text:
We, the undersigned, had formulated in an open letter dated 20 January 2022, direct questions to BioNTech founder, Prof. Sahin, regarding the quality and safety of the Covid-19 vaccines used since recently and have not yet received a direct answer. Based on the open letter, questions were also posed to BioNTech by Berliner Zeitung. Thankfully, some of the questions from the Berliner Zeitung have now been answered by Biontech, although the answers given by BioNTech are in part quite unspecific, so that the concerns we had expressed are by no means dispelled. Furthermore, some of BioNTech’s statements give rise to new questions, which we would like to address in more detail below, also in order to clarify the concerns we have expressed in terms of quality assurance for the new vaccines.
BioNTech responded regarding our concerns about the ALC-0159 and ALC-0315 materials used in the manufacture of the lipid nanoparticles, stating, “The materials used in the vaccine are manufactured and tested using applicable quality requirements (Good Manufacturing Practice). They are approved for use in or on humans as a component of our COVID-19 vaccine.”
Of course, we assume that the materials used are manufactured and tested using valid quality requirements. This is what we expect from any product of the chemical or pharmaceutical industry. With regard to the additives ALC-0159 and ALC-0315, specific obligations were issued by the regulatory authority EMA as part of the conditional approval of the COVID-19 vaccine. These are still described as ongoing in the application for the annual renewal (Procedure no.: EMEA/H/C/005735/R/0046) of the conditional marketing authorization. Why have these conditions not been fulfilled so far and what is the current status of the studies on these important conditions, which also relate to the additives ALC-0159 and ALC-0315?
To the questions we asked about the comparability of the individual batches, i.e. about quality assurance, e.g. to control the concentration of mRNA active ingredient and how the concentration of active ingredient in the lipid nanoparticles is ensured in relation to that outside the particles, BioNTech unfortunately answered very unspecifically and generally:
The combination of lipid nanoparticles and mRNA has been investigated for several decades and is documented in a large number of publications. For example, the following publication in the scientific journal Nature Reviews provides a comprehensive overview: Lipid nanoparticles for mRNA delivery by Hou et al (2021).The quality of each batch is extensively tested by the manufacturer and, independently, also by the responsible federal authority. In Germany, this is the Paul Ehrlich Institute.
Indeed, the use of mRNA as an active ingredient as well as the use of LNP dispersions as drug delivery systems has been investigated for quite some time. To our knowledge, LNP dispersions have only been used in cancer therapy and the treatment of other severe diseases and symptoms (e.g. post-operative pain, RDS in premature infants), as well as for the formulation of amphotericin B (treatment of invasive fungal infections in special cases) and drugs for the treatment of rare diseases for which there are practically no other therapeutic options. For such severe diseases, LNP dispersions may be able to achieve a good risk-benefit ratio. However, for less severe diseases, the situation is different, and more attention needs to be paid to side effects. Quality control review by the Paul Ehrlich Institute (PEI) makes sense, although we wonder to what extent this review is done. Are independent investigations carried out here or are only the test protocols checked? Here we reserve the right to ask the PEI directly.
In response to the question about the color, which is described as a “white to grayish-white dispersion”, BioNTech explains “The term “white to grayish-white dispersion” is a “terminus technicus” used in the description of pharmaceutical products. In English, it is “white to off-white.” In German, this corresponds most closely to “off-white” or “cream-white” — and less to a “gray”. Products containing nanoparticles are generally characterized by this property.” They further explain “A comparable effect also leads to the white color in milk.”
“Here, the impression of white milk is created by the scattering and reflection of light by the fat globules in the surface layer.”
We have to note that the information given in the German-language supplement (“weiß bis grauweiß”) is at least misleading, which does not seem helpful to us. Thus, the correct shade is “off-white” to “creamy white”. Unfortunately, it is still not clear whether the color is uniform or whether there are different shades between “white” and “creamy white” depending on the batch.
The hue of dispersion is largely caused by the superposition of light scattering and light absorption (as well as the viewing angle relative to the incident light). Therefore, it is influenced by the refractive index, size and shape of the colloidal particles, as well as by the absorption spectrum of the substances used, taking into account their molecular interactions in the particles or with the dispersion medium. The color shade thus reflects details of the complex structural composition of the dispersions and the specific properties as well as the purity of the substances used.
If the particle size distribution of the dispersion changes, for example due to agglomeration or coalescence, the color impression would probably also change. Therefore, we assume that BioNTech would not recommend physicians to use a vaccine with a grayish hue.
Certainly, none of us would recommend drinking milk with a grayish hue either. We thank the company for pointing out that not all substances used are colorless. We would like to kindly ask BioNTech to tell us which substances are not colorless. What is the purity of the substances used and which substances are the respective impurities?
Regarding the inquiry about the accumulation of side effects with certain batch numbers, BioNTech answered “Where does this information come from? Unfortunately, this claim was published without citing any sources. To date, BioNTech is not aware of any batch-specific adverse event reports.”
We find this response somewhat irritating. We got our information from the “How bad is my batch” website, which as it states is based on data from the VAERS database. Thereby one finds a certain accumulation of side effects with certain batch numbers. We just wanted to know whether the data listed there are valid and whether analogous data are also collected by BioNTech within the framework of pharmacovigilance according to batch numbers. Such data will certainly be collected as part of the currently ongoing clinical study III, especially for the already known side effects such as myocarditis. This side effect is also listed in the package insert. Is such data also collected for Germany? Are there also batches here in which side effects occur more or less frequently? What investigations into the causes of the side effects are being carried out or are planned?
With regard to quality assurance, BioNTech continues to state: “Each manufactured batch of Comirnaty vaccine is subject to extensive quality testing. The control comprises 12 test parameters at the level of the active ingredient (mRNA), as well as 21 test parameters at the level of the vaccine. The identity, composition, strength, purity, absence of product- and process-related impurities, as well as the microbiological purity of the respective product batch are evaluated and checked against the defined specifications. A batch is only released if the batch meets all quality requirements. Furthermore, each finished product batch is subjected to an additional quality control by an independent, officially supervised control laboratory. These are performed with vaccine vials from the respective batch and for every batch. Only after successful completion of all testing are batches released for vaccination.”
Again, we appreciate that the company says that extensive quality testing is carried out, although we would be pleased to have access to the list of test parameters, along with the permitted deviations. It would also be interesting to know what the specifications are. Furthermore, it would be interesting to know how the additional quality control is carried out by the independent officially supervised control laboratory and which of the test parameters are validated here. Are the 12 test parameters at the API (mRNA) level also validated by an independent control?
Unfortunately, the answers given by BioNTech so far raise more questions than they answer. Urgent questions regarding the side effects of the ‘vaccines’ and their causes still remain unanswered.
Furthermore, BioNTech has so far not addressed our question regarding the side effects occurring instantaneously after vaccination. Such side effects are certainly not related to the formation of the spike proteins, but are more likely to be due to a toxic or allergic reaction.
In this respect, further studies on the ingredients could help. Therefore, we ask whether such studies are underway or planned to increase the safety of the new mRNA vaccines? In our view, critical questions and transparent answers are indispensable in the sense of due diligence, especially in such a case of only conditional approval, which nevertheless affects practically everyone.
Precisely because we consider vaccines and medicines to be important pillars of medicine, careful examination of effectiveness and safety is a basic prerequisite for their use; of course, this also includes excellent quality of the vaccine as well as transparency of quality control.
Prof. Dr. Jörg Matysik, Analytical Chemistry, University of Leipzig (contact)
Prof. Dr. Gerald Dyker, Organic Chemistry, Ruhr University Bochum
Prof. Dr. Andreas Schnepf, Inorganic Chemistry, University of Tübingen
Prof. Dr. Tobias Unruh, Condensed Matter Physics, Friedrich-Alexander-University Erlangen-Nuremberg
Prof. Dr. Martin Winkler, Materials and Process Engineering, Zurich University of Applied Sciences
Note: Among others, molecular biologist Emmanuel Wyler of the Max Delbrück Center Berlin has commented on the professors’ letter. We also submitted the questions to the Paul Ehrlich Institute on 26 January, but received no response from them until the evening of 1 February, other than an automated acknowledgement of receipt of our inquiry. The Berliner Zeitung will continue to report on the discourse and has asked BioNTech for a statement on the follow-up questions.
Chemists on the vaccine: “Where does the shade of gray come from?”
Four chemistry professors sent a list of questions to BioNTech founder Sahin. They are concerned about possible quality defects of the vaccine.
BionTech/ Pfizer’s Comirnaty vaccine.
Four renowned scientists address BioNTech founder Ugur Sahin with a letter: Jörg Matysik, Professor of Analytical Chemistry at the University of Leipzig; Gerald Dyker, Professor of Organic Chemistry at the Ruhr University Bochum; Andreas Schnepf, Professor of Inorganic Chemistry at the University of Tübingen; Martin Winkler, Professor Materials and Process Engineering at the Zurich University of Applied Sciences. The professors formulate their letter, which is available to the Berliner Zeitung, in a consciously benevolent manner.
They are fundamentally interested in mRNA technology. They write: “We find the possibility of mRNA to be stabilized in such a way that it can be used for vaccinations very exciting. We understand that this biotechnological innovation can open up very significant new opportunities in medical practice.”
They care about “both overall public health and a successful chemical and pharmaceutical industry,” the professors said. In an interview with the Berliner Zeitung, Jörg Matysik explains, “With the mRNA technology, BioNTech is using a very promising technology, but also a very complex one. This could be successfully used in the future in cancer therapy, for example. Because of the potentially favorable risk-benefit ratio, a cancer patient may also agree to an experimental treatment.” However, the situation is different with the vaccine against Covid-19. Says Matysik, “As chemists, we don’t have the impression that you can use this product as a mass vaccine at this time.”
A key question facing researchers at BioNTech stems from a note in the SUMMARY OF MEDICINAL CHARACTERISTICS, as the package insert. It says, “The vaccine is a white to grayish-white dispersion.” The professors now ask Professor Sahin, the founder and CEO of BioNTech, “How does this significant color difference come about; virtually all the substances used are colorless, so white would be expected. Where does the shade of gray come from? Are these impurities?” Andreas Schnepf explains the problem: “It may well be that a pill, a liquid or a dispersion is colored. But the color gray, i.e., a “diluted black,” is hardly produced in a process that would have been expected. We need to know if it is impure. If a pill is not white, there is a suspicion that something has gone wrong. We need clarification from BioNTech on this.”
“How is consistent product quality ensured?”
Schnepf: “We rightly have very high standards in the medical field in terms of purity and comparability of products.” Schnepf and Matysik are aware of the great difficulties of quality control in mRNA technology. There are few methods, such as light scattering methods, to provide some degree of quality control, they say. Schnepf said, “As scientists, we are very interested in hearing from BioNTech about what methods are used at BioNTech. We’ve had discussions among our colleagues and have not been able to find any starting points on how to ensure quality in mRNA technology for such a large volume of a product.” In their letter, the professors specifically ask, “How is consistent product quality ensured, or rather, how can you ensure that the mRNA to be packaged is present in the lipid nanoparticles, and to what extent? How do you continue to control the concentration of mRNA active ingredient in each batch, and how do you control the concentration of active ingredient in the lipid nanoparticles relative to that outside the particles?”
A second issue of concern to chemists is the “components used in the vaccine that are not approved for human medicine.” This relates to “the components ALC-0159 and ALC 0315 used to form the lipid nanoparticles,” which are “not directly approved for use on or in the human body,” they said. The safety data sheet for ALC-0315 describes “that ALC-0315 irritates both eyes and skin or mucous membranes. Schnepf sees a problem here, “If it can irritate the eyes or skin, what about the relationship to tissue? This is where we need clarity.”
Says Matysik, “BioNTech works with the best substances available to get this complex mixture stable in the first place.” However, this is a very complex process with lipid particles, because it is a process of self-assembly. “It is very difficult to control.” Specifically, the professors ask in their letter, “Are there any current ongoing or planned studies here to localize the post-use whereabouts of the substances, which are, after all, only used as additives? Are there any further planned or ongoing studies to determine the toxicological effects of the substances or their biodegradation products?”
Finally, scientists are concerned with reports of side effects. They are concerned because there appear to be different side effects with different batch numbers. Schnepf: “That shouldn’t really be the case, because the same thing must be in all doses.” However, the researchers believe it is possible that high production pressure could lead to different results in individual batches, but that would be “intolerable,” Schnepf said. The researchers want to know from BioNTech whether “side effects are correlated with a low number of batch numbers.” Specifically, they ask in their letter, “How can this circumstance be explained and what distinguishes these batches from the others, and are efforts underway to investigate this important aspect in more detail, especially with regard to quality assurance? Are there or are there clinical studies planned to look into the side effects and their causes, as well as to increase the safety of the new Covid vaccines?”
Finally, the chemists write, “Some side effects occur rapidly after vaccination, much more rapidly than would be expected if this were related to the formation of the spike protein. Here, a toxic or allergic reaction would be more likely, and this could be narrowed down by further investigation of the ingredients.” They ask Sahin if “such investigations are underway or planned.” Overall, Matysik says, “there needs to be a much stronger focus on the side effect issue and also involve physicians, who after all have to advise patients, in this discussion.”
The chemists are now waiting for answers from BioMTech. However, because of the importance of the matter, they are considering sending an extended list of questions to the authorities responsible for drug safety, such as the Paul Ehrlich Institute (PEI). Andreas Schnepf: “For a law on compulsory ‘vaccination’, the Bundestag, but also every individual who is vaccinated, needs a sustainable basis of knowledge in order to be able to make an informed, personal decision.” With the “current information provided by BioNTech,” this data basis is not yet established with regard to the Covid-19 vaccines, he said.
Berliner Zeitung has asked BioNTech and the PEI for comments on the scientists’ questions.
Original article (German)