A group of German and Swiss chemists is interested in the mRNA technology used by BioNTech to manufacture the contents of the injections intended to mitigate the effects of the Wuhan Coronavirus. They have sent the company a series of questions about the methodology employed to assure the effectiveness and safety of the treatments, and are hoping to receive useful information in reply.

Many thanks to Hellequin GB for translating this article from the Berliner Zeitung:

Chemist on vaccine: “Where does the shade of grey come from?”

Four chemistry professors sent a list of questions to BioNTech founder Sahin. They are concerned about possible quality issues with the vaccine.

Four renowned scientists wrote a letter 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 formulated their letter, which was made available to the Berliner Zeitung, in a deliberately benevolent manner. They are fundamentally interested in mRNA technology.

They write: “We find the possibility of stabilizing mRNA in such a way that it can be used for vaccinations very exciting. We understand it is important to them both for general public health and for a successful chemical and pharmaceutical industry,” according to the professors.

Jörg Matysik explains in an interview with the Berliner Zeitung: “With the mRNA technologist, BioNTech uses a very promising but also a very complex technology. This can be used successfully in future, for example, in cancer therapy. Because of the possibly good risk-benefit 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 don’t have the impression that this product can currently be used as a mass vaccine.”

A central question that the researchers at BioNTech are asking arises from a note which says: “The vaccine is a white to off-white dispersion.” The professors now ask Professor Sahin, the founder and CEO of BioNTech: “How does this significant color difference come about? Almost all substances used are colorless, so white would be expected. Where does the shade of grey come from? Are these impurities?” Andreas Schnepf explains the problem: “It’s possible that a pill, a liquid or a dispersion is colored. But the color grey, i.e. a “diluted black”, is hardly created in a process that would have been expected. We need to know if it is a contamination. With a pill that is not white, there is a suspicion that something has gone wrong. We need clarification from BioNTech here.”

“How is a uniform product quality-assured?”

Schnepf: “We rightly have very high standards in the medical sector when it comes to the purity and comparability of products.” Schnepf and Matysik are aware of the great difficulties of quality control in mRNA technology. There would be few methods, such as light scattering methods, to provide any degree of quality control. Schnepf: “As scientists, we are very interested in learning from BioNTech which methods are used at BioNTech. We discussed with colleagues and so far 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 ask specifically: “How is uniform product quality ensured, or how can you make sure that and to what extent the mRNA to be packaged is present in the lipid nanoparticles? Furthermore, how is the concentration of mRNA drug in each batch controlled and how the concentration of drug inside the lipid nanoparticles relative to that outside the particles?”

A second problem that worries the chemists is the “components not approved for human use” used in the vaccine. This applies 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 irritates both the eyes and the skin or mucous membranes”. Schnepf sees a problem here: “If it can irritate the eyes or the skin, what about the relationship to the tissue? We need clarity here.” Matysik: “BioNTech works with the best substances available to make this complex mixture stable at all.” However, this is a very complex process with lipid particles, because it is a process of self-organization. “Controlling it is very difficult.” Specifically, the professors ask in their letter: “Are there currently ongoing or planned studies to localize the whereabouts of the substances, which are only used as additives, after application? Are there any other planned or ongoing studies to determine the toxicological effects of the substances or their biological degradation products and to locate them after the application?”

Then the scientists deal with reports of side effects. They are concerned because there appear to be different side effects with different batch numbers. Schnepf: “It really shouldn’t be, because all the containers have to contain the same stuff.” However, the researchers believe it is possible that the high production pressure could lead to different results in individual batches, which 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 fact be explained, and what distinguishes these batches from the others, and are efforts underway to investigate this important aspect more closely, especially with regard to quality assurance? Are there or are clinical studies planned to investigate the side effects and their causes and to increase the safety of the new Covid vaccines?”

“Informed Decision”

Then the chemists write: “Some side effects occur immediately after vaccination, much faster than one would expect if they were related to the formation of the spike protein. A toxic or allergic reaction would be more likely here, which could be narrowed down by further investigations into the ingredients.” They ask Sahin whether “such investigations are ongoing or planned.” All in all, according to Matysik, “the problem of side effects must be given much more focus, and physicians, who have to advise their patients, must also be involved in this discussion.” The chemists are now waiting for answers from BioNTech. However, they are considering sending an extended catalog of questions to the authorities responsible for drug safety, 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 is vaccinated, needs a solid basis of knowledge in order to be able to make an informed, personal decision”. With the “current information available from BioNTech”, this data basis is not yet available with regard to the Covid 19 vaccines.

The Berliner Zeitung asked BioNTech and the PEI for statements on the scientists’ questions. We will continue reporting after receiving the comments.