**Chemist on vaccine: "Where does the gray shade come from?“** Four chemistry professors sent a list of questions to BioNTech founder Sahin. They are concerned about possible quality defects of the vaccine. Four renowned scientists have written to BioNTech founder Ugur Sahin: 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 deliberately formulate their letter, which is available to the Berliner Zeitung, benevolently. They are fundamentally interested in mRNA technology. They write: "We find the possibility of stabilizing mRNA so 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.“ According to the professors, it is "due to general public health as well as to a successful chemical and pharmaceutical industry". Jörg Matysik explains in an interview with the Berliner Zeitung: "With the mRNA technologist, BioNTech is using a very promising, but also a very complex technology. In the future, this can be successfully used, for example, in cancer therapy. Because of the potentially good benefit-risk ratio, a cancer patient may also agree to an experimental treatment.“ However, the situation is different with the vaccine against Covid-19. Matysik: "As chemists, we do not have the impression that this product can currently be used as a mass vaccine.“ A central question that arises for the researchers at BioNTech arises from a note in which it says here: "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; almost all the substances used are colorless, so white would be expected. Where does the gray shade come from? Are these impurities?" Andreas Schnepf explains the problem: "It may already be that a pill, a liquid or a dispersion is colored. But the color gray, i.e. a "diluted black", hardly arises in a process that would have been expected. We need to know if it is an impurity. With a pill that is not white, there is a suspicion that something went wrong there. We need information from BioNTech here.“ "How is uniform product quality ensured?“ Schnepf: "We rightly have very high standards in the medical field with regard to the purity and comparability of products." Schnepf and Matysik are aware of the great difficulties of quality control in mRNA technology. There are only a few methods, such as light scattering methods, to enable quality control to a certain extent. "As BioNTech scientists, we are very interested to learn from BioNTech which methods are used at BioNTech. We have discussed in the team and so far we have not been able to find any starting points on how to ensure the quality of mRNA technology for such a large volume of a product." In their letter, the professors specifically ask: "How is a uniform product quality ensured, or how can you ensure that and to what extent the mRNA to be packaged is present in the lipid nanoparticles? How is the concentration of mRNA active substance in the individual batches controlled and how is the concentration of active substance in the lipid nanoparticles compared to that outside the particles?“ A second problem that concerns the chemists is the "components not approved for human medicine" used in the vaccine. This relates to "the components ALC-0159 and ALC 0315 used for the formation of the lipid nanoparticles", which are "not directly approved for use on or in the human body". The safety data sheet for ALC-0315 describes "that ALC-0315, both eyes and skin or mucous membrane" irritates. Schnepf sees a problem here: "If it can irritate the eyes or the skin, what about the relationship to the tissue? Here we need clarity." Matysik: "Biontech works with the best available substances to get this complex mixture stable at all". However, this is a very complex process for lipid particles, because it is a process of self-organization. "Control is very difficult." Specifically, the professors ask in their letter: "Are there currently ongoing or planned studies to locate the whereabouts of the substances, which are only used as additives, after application? Are there still planned or ongoing studies to determine the toxicological effects of the substances or their biodegradation products?“ After all, scientists are dealing with reports of side effects. They are worried because there are apparently different side effects with different batch numbers. Schnepf: "It really shouldn't be, because it has to be the same inside in all doses." However, the researchers believe it is possible that the high production pressure could lead to different results for individual batches, but this is "not tolerable," says Schnepf. The researchers want to know from BioNTech whether "the side effects are correlated with a small 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 study this important aspect in more detail, especially with regard to quality assurance? Are there or are clinical studies planned to investigate the side effects and their causes as well as to increase the safety of the new Covid vaccines?“ "Informed decision" Finally, the chemists write: "Some side effects occur quickly after vaccination and much faster than one would expect if this were related to the formation of the spike protein. Here, a toxic or allergic reaction would be more likely, which could be narrowed down by further studies on the ingredients." They ask Sahin whether "such investigations are underway or planned". Overall, according to Matysik, "the side effect problem should be given much more focus and doctors, who have to advise patients, should also be involved in this discussion". The chemists are now waiting for answers from BioNTech. However, they are considering sending an extended list of questions to the authorities responsible for the safety of medicines, such as the Paul Ehrlich Institute (PEI), because of the importance of the matter. Andreas Schnepf: "For a law on compulsory vaccination, the Bundestag, but also every individual who gets vaccinated, needs a viable basis of knowledge in order to be able to make an informed, own decision". With the "currently available information available from BioNTech", this data basis is not yet available with regard to the Covid-19 vaccines. The Berliner Zeitung has asked BioNTech and the PEI for comments on the scientists' questions. We will continue reporting after receiving the comments. https://www.berliner-zeitung.de/news/chemiker-zu-impfstoff-woher-kommt-der-grauton-li.208305