In the biotechnology industry, a compendial standard refers to a set of guidelines, specifications, or standards developed by regulatory agencies, scientific organizations, or trade associations to ensure the quality, safety, and efficacy of biological products, such as vaccines, therapeutics, diagnostics, and other biologics.
Additional critical assays, including residual host cell and process-related impurities such as DNA, proteins, DNAase may be generic but have impact on product safety and integrity.
It is vital that people know that endosomal escape has been a major hurdle in the development of successful RNA therapeutics because it is LNP topology-dependent. And because “Antigen expression is proportional to the number of conventional mRNA transcripts successfully delivered [or produced] during “vaccination”, we have no definitive quantitative definition of dose.
It is clear that good manufacturing practices were not adhered to, and critical quality attributes were not assessed properly when the COVID-19 commercial products were upscaled and produced using the DNA plasmid/E. coli system because DNA is in the vials. We hypothesize that the DNAase that is traditionally used to degrade the residual DNA - the necessary by-product of the modified mRNA synthesis process - was ineffective because it failed to work on DNA:RNA hybrids that formed. This allowed for the transfer and subsequent packaging of DNA and DNA:RNA hybrids into LNPs. The problem with this is that DNA:RNA hybrid formation involves excised introns called R-loops, and if these hybrids with their R-loops are exogenously introduced via lipid nanoparticles into cells, accumulation can induce disease states including cancer. This is well-documented in the literature.