Modular multiplatform system for mrna drug production
AssigneeBioNTech SE
InventorsRainer Kröner, Semra Kati, Florian Krämer, Jonas Hennekes
Life of this patent
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Abstract
A drug production facility includes: a first module comprising drug substance and drug product manufacturing equipment including equipment for producing RNA-based drug substance, lipid nanoparticle (LNP)-based drug products and lipoplex-based drug products; and a second module that includes fill and finish process equipment.
Claims84
A drug production facility comprising:
- a first module comprising drug substance and drug product manufacturing equipment comprising equipment for producing RNA-based drug substance, lipid nanoparticle (LNP)-based drug products and lipoplex-based drug products;
- and
- a second module comprising fill and finish process equipment.
A method of selectively producing a filled container containing an RNA-based drug product at a production facility comprising a first module and a second module, the method comprising:
- producing an RNA-based drug substance within the first module, wherein producing drug substance comprises:
- performing in vitro transcription (IVT);
- performing at least one of a tangential flow filtration (TFF) step and a hydrophobic interaction chromatography (HIC) step;
- and
- performing at least one filtration step following TFF and/or HIC;
- producing, within the first module, a lipid-based drug product that comprises the RNA-based drug substance, the lipid-based drug product comprising at least one of a lipoplex particle and a lipid nanoparticle (LNP);
- and
- performing a filling process, within the second module, comprising filling at least one fluid container with the lipid-based drug product.
A portable system for producing a formulation comprising an mRNA-based product, the system comprising:
- a first sub-system comprising a drug substance formulation module, the first sub-system comprising:
- transcription equipment for forming an RNA solution via in vitro transcription;
- and
- a second sub-system operatively downstream of the first sub-system comprising multiple drug product formation modules, the second sub-system comprising:
- an LNP formation module for producing an RNA-LNP preparation from the RNA solution;
- a lipoplex formation module for producing an RNA lipoplex preparation from the RNA solution;
- and
- a buffer preparation module,
- wherein the portable system is contained within an area no larger than about 75 square meters.
A facility comprising the system of any of the previous claims, the facility further comprising a portable fill and finish module.
A method for making liposomes in a modular and/or portable production facility, the method comprising:
- adjusting a lipid concentraction within a first solution;
- adding the lipid concentration to, and mixing it with, ethanol;
- sterilizing the mixture via filtration;
- injecting the filtered mixture into a spinner flask;
- stirring the filtered mixture within the spinner flask;
- continuing injection of the mixture into the spinner flask until a desired lipid concentration is reached;
- filtering the mixture, thereby forming filtered liposomes;
- and
- diluting the filtered liposomes.
A method for making lipoplexes in a modular and/or portable production facility, the method comprising:
- providing an RNA solution and a liposome solution to the modular and/or portable production facility;
- adjusting a concentration of RNA in the RNA solution to a concentration of liposomes in the liposome solution;
- adding NaCl to the RNA solution for condensation of the RNA;
- and
- mixing the RNA solution and the liposome solution, thereby forming a lipoplex solution.
A portable system for producing a formulation comprising an mRNA-based product, the system comprising:
- a first sub-system comprising a drug substance formulation module, the first sub-system comprising:
- equipment for forming an RNA solution;
- and
- a second sub-system comprising multiple drug product formation modules, the second sub-system comprising:
- an LNP formation module for producing an RNA-LNP preparation from the RNA solution and a lipid solution;
- and
- a lipoplex formation module for producing an RNA-lipoplex preparation from the RNA solution and a liposome solution;
- wherein the portable system is configured to selectively produce each of the RNA-LNP preparation and the RNA-lipoplex preparation using the RNA solution.
A method for making RNA lipid nanoparticles (LNP) in a modular production facility, the method comprising:
- providing an acidified aqueous phase, an RNA solution, and a lipid solution to the modular production facility;
- mixing the acidified aqueous phase with the lipid solution, thereby forming a mixture;
- performing at least one of filtration, bioburden reduction, freezing, and dilution on the mixture, thereby forming preformed LNPs;
- and
- mixing the RNA solution and the preformed LNPs, thereby forming the RNA lipid nanoparticles.
A modular drug production facility (or module) comprising a combined process flow capable of producing both lipid nanoparticle (LNPs) and lipoplexes, the facility (or module) comprising:
- an LNP formation module;
- a lipoplex formation module;
- a lipid supply;
- and
- a drug substance/RNA formation module;
- wherein each of the LNP formation module and the lipoplex formation module are fluidly coupled downstream of both the lipid supply and the drug substance/RNA formation module.
An RNA mixture comprising:
- from about 42% to about 54% RNA solution by volume;
- from about 8% to about 28% elution buffer by volume;
- and
- from about 30% to about 38% dilution buffer by volume.
The method of 36, wherein the liposome solution comprises cationic lipids.
The method of 36, wherein the liposome solution comprises at least one of a cationic lipid, an ionizable aminolipid, and a helper lipid.
Dependencies are inferred from the claim text.