Next Generation Tools in mRNA Purification: The Role of Continuous Raman Spectroscopy Testing with Pretreatment of the Sample
In biopharmaceutical productions field the purification proces is a crucial step in order to obtain Drugs whit impurity profile according the regulatory agency requirement. Aim of this work is to verify some relevant and recent literature and after analysis to submit to the researcher new Solutions in order to improve the global safety and the toxicological profile: is submitted a project related the in continuous testing of the purified materials using Raman spectroscopy - with pretreatment of the sample.
Introduction
In various biopharmaceutical productive process the final purification is a relevant step and are used in example various chromatographic process using different systems (resins, column, monoliths).
Various materials are used for the stationary phase.
Some vials of mRNA vaccine was analyzed by independent researcher in order to verify the profile of impurity [1].
Many classic and biological drugs use activated carbon for purification of water needed (pirogen) and in commerce there are producers that use composite materials in their monoliths (carbon based) [2, 3].
In recent time great public debate was involved in finding of graphene like particle in some C19 vials of vaccine as well as in blood of many vaccinated people [4]. According regulatory agency it is accepted RAMAN spectroscopy also direct to verify impurity in the pharmaceutical product [5]. But this method (the direct one assay), when applied to Nano lipids, according literature is not the best way to test the payload of the nanoparticle [6].
To increase the possibility to find all impurity it is crucial to pretreat the sample (Nano lipids) with solvent before preform the RAMAN test.
Material and Methods
With an observational point of view some relevant literature is reported and an hypothesis of work is then submitted to increase the global safety related some impurity for the Nano lipids based drugs production.
Results
From literature: as reported in reference form Luisetto, et al. [1, 2, 3, 4, 5, 6, 7]. “Because in various API manufacturing process are used AC products it is necessary to test the final impurity also for graphene: this is due by the different size of the particle of amorphous AC vs crystalline exfoliated graphene. (also for genotoxicity) and the toxicity that can be produced also below the threshold for impurity.
The AC production can imply really high temperature with chemico - physical change. The pharmacopeia monography for AC not cite the word graphene” [8].
Experimental Project Hypothesis
In order to increase the power of detecting impurity in Nano lipids drugs it is necessary at the end of the production process to test in continuous way the final product using RAMAN spectroscopy (with pretreatment of the sample). In this way only after use of solvent t is possible to avoid the interference played by the Nano lipids.
Discussion
In Literature is Reported
- The crucial role played by the purifications steps.
- Various chromatographic procedures are used, using resins and monoliths.
- Some producers use activates carbon composite materials.
- For production of water for injectable (Pirogen) are used also charcoal filter systems membrane.
- The test for PAT (Proces Analytical Technology) analysis in pharmaceutical production use also Raman Spectroscopy.
- It is allowed by regulatory agency the direct testing whit RS (without pretreatment with solvent of the sample).
- This method is not the best to test the payloads for Nano lipids drugs. According Vanden-Hehir S, et al. “A major advantage of Raman is that it allows direct imaging of the Nano carriers, and not the payload en-capsulated within them.”
- Independent researcher finded graphene like particle in some vials of some C19 vaccine [1].
- Other researcher finded graphene particle in blood of vaccinated [4].
- From membrane of activated carbon can be released impurity.
- One method to produce water for injection (pirogen remove) is using activated carbon.
- (The same in order to remove pirogen from injectable).
- Activated charcoal is produced also using really high temperature and it can exfoliate graphite and graphene [8] even if under the threshold requirement of the regulatory agency.
- In monography of activated carbon of various pharmacopeia the term graphene is not reported.
Conclusion
For all reported in discussion i is opinion of the authors that to increase the level of safety in mRNA Production and purifications it is necessary to test the final product in biopharmaceutical production in continuous way using a Raman Spectroscopy with pretreatment of the sample with solvent. This to avoid interference played by the Nano lipids.
Also for the classic chemical drugs and their productive process it is of interest to verify the absence of impurity form activated carbon membrane used related the level today admitted (thresholds) by pharmacopeia.
What are the toxicological effect played by some impurity if present in drugs final product also under the regulatory thresholds?
The m RNA purifications steps can be improved using new technology, classic chemical analytical tests whit pretreatment of the samples and performed in continuous way.
Conflict of Interest
No
References
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Campra P (2021) Detection of Graphene in Covid19 Vaccines.
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Luisetto M, Ahmadabadi NB, Ettarhouni ZO, Edbey K, Latyshev OY (2022) Monoliths in the mRNA Vaccine Purification Process the Silica Resin and Other Composite Materials: The Carbon Content. International Case Reports Journal 2(7): 1-23.
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Luisetto M, Edbey K, Tarro G, Ahmadabadi NB, Khan FA, et al. (2023) Activated Charcoal and Derivate Materials in Drugs and Biopharmaceutical Purification: Impurity Aspects. Journal of Materials Science and Nanotechnology 11(1): 1-31.
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Cipelli RB, Giovannini F, Pisano G (2022) Dark -Field Microscopic Analysis on the Blood of 1,006 Symptomatic Persons After Anti-COVID mRNA Injections from Pfizer/ BioNtech or Moderna. International Journal of Vaccine Theory, Practice, and Research 2(2): 385-444.
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Luisetto M, Nili B, Edbey K, Tarro G, Cabianca L, et al. (2022) Raman (Rs) Spectroscopy for Biopharmaceutical Quality Control and PAT. Raw Material - Final Products: the Nanolipids Effect on Signal Intensity. Regulatory and Toxicological Aspects. Medicinal and Analytical Chemistry International Jornal 6(1): 1-17.
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Vanden-Hehir S, Tipping WJ, Lee M, Brunton VG, Williams A, et al. (2019) Raman imaging of nanocarriers for drug delivery. Nanomaterials 9(3): 341.
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Activated charcoal BP monography.
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Luisetto M, Edbey K, Nili B, Khan FA, Cipelli RB, et al. (2023) Amorphus Substantie (Activated Charcoal) And Other Impurities in API Manufacturing Process. Pharmaceutical, Toxicological And Regulatory Implication. World journal of pharmaceutical research.
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