MANUFACTURER’S CONVENIENCE FOR RESIDUAL DNA
The FDA Briefing Document. Vaccines and Related Biological Products Advisory Committee Meeting September 19, 2012: Cell Lines Derived from Human Tumors for Vaccine Manufacture.
This FDA document teaches us the risks associated with the residual DNA. Let's take a look at some interesting statements about the regulation value of 10 ng for the residual DNA.
When the first to third reasons are applied to the DNA wrapped in the LNP (LNP-DNA), the second and third reasons are not appropriate for the LNP-DNA because they did not take the LNP into account. The LNP had not yet been invented in 1997.
That is, for the LNP-DNA, the regulation value of 10 ng is based solely on the first reason, "manufacturer's convenience."
This FDA document contains multiple sources of information and will be of public interest.
Incidentally, in my field, it is commonly believed that Arbutus Biopharma Corp holds the dominant patent US8058069B2 for the LNP. This patent was filed on April 15, 2009, and granted on November 15, 2011.
Even looking at the citation 10, no specific information was found.
The outcome of the 1997 WHO meeting was that the amount of residual cell-substrate DNA allowed per dose in a vaccine produced in a continuous cell line and one administered by the parenteral route was raised from 100 pg to 10 ng (10).
The WHO document published in 1998, the year after 1997, contained more detailed information (see page 25), but I could not find anything equivalent to the FDA document.
However, this WHO document has an interesting information.
The new upper limit of 10ng of residual DNA per dose does not apply to products derived from microbial, diploid or primary-cell-culture systems. The 1986 WHO Study Group stated that the risks for con-tinuous-cell-line DNA should be considered negligible for preparations given orally; for such products, the principal requirement is the elimination of potentially contaminating viruses and toxic proteins.
The upper limit of 10ng of residual continuous-cell-line DNA per dose therefore does not apply to a product given orally. Acceptable limits should be set in consultation with the national control author-ity.
The critics of the DNA contamination issue sometimes contrast the DNA that contaminates vaccines with the food DNA. In this point, the 10 ng residual DNA contamination limit does not apply to the oral vaccines (see WHO document, p. 25 to 27). This is because the risk is lower compared to subcutaneous or intramuscular injections. In the case of the oral products , the DNA is broken down during the digestion process.
Such structure of regulation also highlights the inconsistency of discussing food DNA and DNA contaminating vaccines in the same category.
If you have any information related to those please let me know.
Great information, thanks. Have just added here:
https://geoffpain.substack.com/p/bacterial-dna-a-major-worry-in-jabs
Thanks!