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Five professors want to know more about the vaccine against Covid 19 from BioNTech. The company’s first answers raise new questions.
Sort code , February 1, 2022 – 9:45 p.m
Four chemistry professors asked questions to BioNTech. It’s about consistency and quality of the Covid-10 vaccine (here) . The company responded to this (here) . But for the scientists, who meanwhile are joined by Prof. Dr. Tobias Unruh, Condensed Matter Physics, Friedrich-Alexander-University Erlangen-Nuremberg, a fifth colleague, the answers from BioNTech raise new questions. The Berliner Zeitung documents the questions of the professors in the following in the wording:
In an open letter dated January 20, 2022 , we, the undersigned, formulated questions directly to BioNTech founder, Prof. Sahin, regarding the quality and safety of the Covid-19 vaccines that have recently been used and have not yet received a direct answer. Based on the open letter, questions were also asked of BioNTech by the Berliner Zeitung. Thankfully, some of the questions from the Berliner Zeitung have now been answered by BioNTech, whereby the answers given by BioNTech are partly quite unspecific, so that the concerns we have expressed are by no means dispelled. Furthermore, some statements by BioNTech give rise to new questions, which we would like to discuss in more detail below, also in order to clarify the concerns we have expressed in terms of quality assurance for the new vaccines.
Responding to our concerns about the ALC-0159 and ALC-0315 substances used in the manufacture of the lipid nanoparticles, BioNTech responded : “The materials used in the vaccine are manufactured and tested using applicable quality requirements (Good Manufacturing Practice). They are approved for use on or in humans as part of our COVID-19 vaccine.”
Of course, we assume that the materials used are manufactured and tested using the applicable quality requirements. We expect that from every product in the chemical and pharmaceutical industry. With regard to the additives ALC-0159 and ALC-0315, the approval authority EMA has issued specific obligations as part of the conditional approval of the COVID-19 vaccine . When applying for the annual extension ( Procedure no.: EMEA/H/C/005735/R/0046 ) of the conditional approval, these are still considered ongoing ( ongoing) described. Why have these requirements not yet been met or what is the current status of the studies on these important requirements, which also affect the additives ALC-0159 and ALC-0315?about:blank
Unfortunately, BioNTech gave very good answers to the questions we asked about the comparability of the individual batches, ie quality assurance, e.g. to control the concentration of mRNA active substance and how the concentration of active substance in the lipid nanoparticles is ensured in relation to that outside the particles nonspecific and general: The combination of lipid nanoparticles and mRNA has been studied for several decades and is documented in a large number of publications. A comprehensive overview is given, for example, in the following publication in the scientific journal Nature Reviews: Lipid nanoparticles for mRNA delivery by Hou et al. (2021).
The quality of each batch is extensively checked by the manufacturer and, independently, by the responsible federal authority. In Germany, this is the Paul Ehrlich Institute.
In fact, the use of mRNA as a drug as well as the use of LNP dispersions as drug delivery systems have been studied for some time. To our knowledge, LNP dispersions have so far only been used in cancer therapy and the treatment of other serious illnesses and symptoms (e.g. postoperative pain, IBS in premature babies) and for the formulation of amphotericin B (treatment of invasive fungal infections in special cases) and medicines for Treatment of rare diseases for which there are practically no other treatment options. In such severe diseases, a good risk-benefit ratio can possibly be achieved with the LNP dispersions. In the case of less serious illnesses, however, the situation is different, and the side effects must be taken into account more closely. The review of quality control by the Paul Ehrlich Institute (PEI) makes sense, although we wonder to what extent this review takes place. Are independent investigations carried out here or are only the test protocols checked? Here we reserve the right to ask the PEI directly.Recommended by
When asked about the color , which is described as “white to off-white dispersion,” BioNTech explains, ” The term “white to off-white dispersion” is a “technical term” used to describe pharmaceutical products. In English it is “white to off-white”. In German, this corresponds most closely to the terms “off-white” or “cream white” – and less to “grey”. Products that contain nanoparticles are generally characterized by this property.” They further explain “ A comparable effect also leads to the white color of 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 state that the information given in the German-language supplement (“white to off-white”) is at least misleading, which we don’t find helpful. The right color is therefore “off-white” to “cream white”. Unfortunately, it is still not clear if the color is uniform or if there are different shades between “white” and “cream white” depending on the batch.
The hue of the dispersion is primarily caused by the superimposition of light scattering and light absorption (as well as the viewing angle relative to the incident light). It is therefore 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 tone 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 the company BioNTech would not recommend doctors to use a vaccine with a greyish hue. Certainly none of us would recommend drinking milk with a greyish tint either. We thank the company for pointing out that not all substances used are colorless. Here we would like to kindly ask BioNTech to tell us which substances are not colorless. What is the purity of the substances used and what are the substances involved in the respective impurities?
Regarding the query about the accumulation of side effects for certain lot numbers, BioNTech replied “Where did this information come from? Unfortunately, this claim was published without acknowledging the source. To date, BioNTech is not aware of any batch-specific adverse event reports.”
We find this answer a bit irritating. We got our information from the website How bad is my batch, which, as stated there, is based on data from the VAERS database. There is a certain accumulation of side effects with certain batch numbers. We just wanted to know whether the data listed there is valid and whether analogous data is also collected by BioNTech as part of pharmacovigilance according to batch numbers. Such data will certainly be collected as part of the current clinical study III, especially for the side effects that are already known, such as myocarditis. This side effect is also listed in the package leaflet. Are such data also collected for Germany? Are there also batches where side effects occur more or less frequently? What investigations into the causes of the side effects are being carried out or are planned?
Regarding quality assurance , BioNTech further states:Each manufactured batch of Comirnaty vaccine is subject to extensive quality testing. The control includes 12 test parameters at the level of the active substance (mRNA) and 21 test parameters at the level of the vaccine. The identity, composition, strength, purity, absence of product and process-related impurities and 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. In addition, each finished product batch is subjected to additional quality control by an independent, officially monitored control laboratory. These are carried out with vaccine vials from the respective batch and for each batch.
Here, too, we welcome the fact that, according to our own statements, extensive quality tests are carried out, and we would be pleased if we were given access to the list of test parameters, including the permitted deviations. It would also be interesting to find out what the specifications are. It would also be interesting to find out how the additional quality control is carried out by the independent, officially monitored control laboratory and which of the test parameters are validated here. Are the 12 test parameters at the level of the active substance (mRNA) also validated by an independent control?
Unfortunately, the answers given so far by BioNTech raise more questions than they provide answers. Urgent questions about the side effects of vaccines and their causes still remain unanswered.
Furthermore, BioNTech has not yet responded to our question regarding the side effects that occur immediately after the vaccination. Such side effects are certainly not related to the formation of the spike proteins, but are more likely to be attributed to a toxic or allergic reaction. In this regard, further investigations into the ingredients could help. So we ask if such research is ongoing or planned to increase the safety of the new mRNA vaccines?
In our opinion, critical questions and transparent answers are indispensable in terms of due diligence, especially in such a case of only conditional approval, which nevertheless affects practically everyone.
Precisely because we consider vaccines and drugs to be important pillars of medicine, careful testing of their effectiveness and safety is a basic requirement for their use; of course, this also includes excellent quality of the vaccine and 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: Emmanuel Wyler from the Max Delbrück Center in Berlin, among others, commented on the letter from the professors (here) . We have the questions on 26.1. also sent to the Paul-Ehrlich-Institut, but received no reply from there until the evening of Monday, February 1, apart from an automated acknowledgment of receipt of our request. The Berliner Zeitung will continue to report on the discourse and has asked BioNTech for a statement on the inquiries.