mroswell/wiseman-usp-proposals.md

## wiseman-usp-proposals.md

      
    Raw
  

              wiseman-usp-proposals.md
            
          
    Of course! Here's the table with a new column added before the original and simplified proposal columns, which includes the proposal numbers:


Proposal Number
Original Proposal
Simplified Proposal


Proposal 1
The USP Draft Guidelines must refer to "mRNA Therapeutics" as being sub-types of "gene therapy products."
Call mRNA vaccines a type of gene therapy.


Proposal 2
The term "Engineered RNA" or "engRNA" be used to describe these products.
Use "Engineered RNA" to talk about them.


Proposal 3
As appropriate, engRNA be used in USP documents, unless context requires a more specific term.
Keep using "engRNA" unless you need a specific word.


Proposal 4
Where appropriate, "modRNA" is used in USP documents, unless context requires the term engRNA.
"ModRNA" means the same as "engRNA" unless needed.


Proposal 5
Where appropriate, the term "Codon Optimized" is used throughout USP documents.
Use "Codon Optimized" when it fits.


Proposal 6
Rather than the term "XX-valent," a term such as "XX-functional" be used in compendial nomenclature for these products.
Instead of "XX-valent," say "XX-functional."


Proposal 7
For vaccine nomenclature, a prefix must reflect the number of antigenic variants.
In vaccine names, show how many types there are.


Proposal 8
Plasmid maps and sequences must be disclosed with justification of target genes. ORIs, enhancers, promoters, antibiotic resistance genes, and assessment of nuclear localization signals.
Share details about genes used, why, and more.


Proposal 9
The presence of intact sequences of particular interest such as ORI’s, promoters, enhancers, antibiotic resistance genes must be assessed in Drug Product by suitable by sequencing or use of suitable primer with qPCR.
Check if important gene pieces are still there using special tests.


Proposal 10
The size distributions of residual DNA fragments must be assessed as quality attributes in Drug Substance and Drug Product by suitable methods.
Check the size of leftover DNA to make sure it's good quality.


Proposal 11
Guidelines must establish limits on residual DNA content of Drug Product that considers the type and effectiveness of transfection agent used (e.g. LNP) used.
Set limits on leftover DNA based on what's used to help genes get in cells.


Proposal 12
Guidelines must establish limits on residual DNA content of Drug Product that considers the presence of replication competent plasmid, intact DNA sequences of functional elements, even if shorter than 200bp.
Set limits on leftover DNA, even if it's short, and check for self-copying DNA.


Proposal 13
Guidelines must establish limits on residual DNA content of Drug Product that considers cumulative exposure occurring due to use of updated versions of provaccines, or other engRNA gene therapies that use the same platform technology.
Consider all the times similar vaccines or treatments are used.


Proposal 14
Validated assays to estimate the risk posed by residual DNA engRNA gene therapy products must be developed and conducted in support of other proposals described here.
Create tests to understand if leftover DNA could be risky.


Proposal 15
Validated assays to estimate the presence of replication competent plasmid in Drug Product must be developed and implemented.
Create tests to find out if there's self-copying DNA in the vaccine.


Proposal 16
Methods must be developed to assess transcriptional infidelity in large samples of DS and to assess its effect on translation and effectiveness of DP.
Develop ways to check if the genetic material has mistakes and if it affects how the vaccine works.


Proposal 17
Guidelines be developed to establish standards for engRNA integrity in Drug Substance and Drug Product.
Make rules to make sure the genetic material in the vaccine is in good condition.


Proposal 18
Assays should be developed to further characterize the translation of truncated or fragmented engRNA species, or the effects of these species on translation.
Create tests to understand how cut or broken genetic material might affect how the vaccine works.


Proposal 19
Assays should be developed to determine the immunomodulatory, immunogenicity risk of double stranded, truncated, or fragmented engRNA.
Make tests to understand if certain broken genetic material affects the immune system.


Proposal 20
Methods must be developed to comprehensively identify expressed protein in terms of amino acid sequence, 3D structure and folding, glycosylation and trimerization.
Develop methods to fully understand the genetic material in the vaccine.


Proposal 21
Methods must be developed to assess potency in a way that takes account of the intended pharmacological action.
Make sure the vaccine is strong and effective for its intended purpose.
Proposal Number	Original Proposal	Simplified Proposal
Proposal 1	The USP Draft Guidelines must refer to "mRNA Therapeutics" as being sub-types of "gene therapy products."	Call mRNA vaccines a type of gene therapy.
Proposal 2	The term "Engineered RNA" or "engRNA" be used to describe these products.	Use "Engineered RNA" to talk about them.
Proposal 3	As appropriate, engRNA be used in USP documents, unless context requires a more specific term.	Keep using "engRNA" unless you need a specific word.
Proposal 4	Where appropriate, "modRNA" is used in USP documents, unless context requires the term engRNA.	"ModRNA" means the same as "engRNA" unless needed.
Proposal 5	Where appropriate, the term "Codon Optimized" is used throughout USP documents.	Use "Codon Optimized" when it fits.
Proposal 6	Rather than the term "XX-valent," a term such as "XX-functional" be used in compendial nomenclature for these products.	Instead of "XX-valent," say "XX-functional."
Proposal 7	For vaccine nomenclature, a prefix must reflect the number of antigenic variants.	In vaccine names, show how many types there are.
Proposal 8	Plasmid maps and sequences must be disclosed with justification of target genes. ORIs, enhancers, promoters, antibiotic resistance genes, and assessment of nuclear localization signals.	Share details about genes used, why, and more.
Proposal 9	The presence of intact sequences of particular interest such as ORI’s, promoters, enhancers, antibiotic resistance genes must be assessed in Drug Product by suitable by sequencing or use of suitable primer with qPCR.	Check if important gene pieces are still there using special tests.
Proposal 10	The size distributions of residual DNA fragments must be assessed as quality attributes in Drug Substance and Drug Product by suitable methods.	Check the size of leftover DNA to make sure it's good quality.
Proposal 11	Guidelines must establish limits on residual DNA content of Drug Product that considers the type and effectiveness of transfection agent used (e.g. LNP) used.	Set limits on leftover DNA based on what's used to help genes get in cells.
Proposal 12	Guidelines must establish limits on residual DNA content of Drug Product that considers the presence of replication competent plasmid, intact DNA sequences of functional elements, even if shorter than 200bp.	Set limits on leftover DNA, even if it's short, and check for self-copying DNA.
Proposal 13	Guidelines must establish limits on residual DNA content of Drug Product that considers cumulative exposure occurring due to use of updated versions of provaccines, or other engRNA gene therapies that use the same platform technology.	Consider all the times similar vaccines or treatments are used.
Proposal 14	Validated assays to estimate the risk posed by residual DNA engRNA gene therapy products must be developed and conducted in support of other proposals described here.	Create tests to understand if leftover DNA could be risky.
Proposal 15	Validated assays to estimate the presence of replication competent plasmid in Drug Product must be developed and implemented.	Create tests to find out if there's self-copying DNA in the vaccine.
Proposal 16	Methods must be developed to assess transcriptional infidelity in large samples of DS and to assess its effect on translation and effectiveness of DP.	Develop ways to check if the genetic material has mistakes and if it affects how the vaccine works.
Proposal 17	Guidelines be developed to establish standards for engRNA integrity in Drug Substance and Drug Product.	Make rules to make sure the genetic material in the vaccine is in good condition.
Proposal 18	Assays should be developed to further characterize the translation of truncated or fragmented engRNA species, or the effects of these species on translation.	Create tests to understand how cut or broken genetic material might affect how the vaccine works.
Proposal 19	Assays should be developed to determine the immunomodulatory, immunogenicity risk of double stranded, truncated, or fragmented engRNA.	Make tests to understand if certain broken genetic material affects the immune system.
Proposal 20	Methods must be developed to comprehensively identify expressed protein in terms of amino acid sequence, 3D structure and folding, glycosylation and trimerization.	Develop methods to fully understand the genetic material in the vaccine.
Proposal 21	Methods must be developed to assess potency in a way that takes account of the intended pharmacological action.	Make sure the vaccine is strong and effective for its intended purpose.