EP-4735159-A1 - MODULAR MULTIPLATFORM SYSTEM FOR MRNA DRUG PRODUCTION

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.

Inventors

• KATI, Semra
• KRÄMER, Florian
• HENNEKES, Jonas
• KRÖNER, Rainer

Assignees

• BioNTech SE

Dates

Publication Date

20260506

Application Date

20240628

Claims (20)

1. 1. 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.
2. 2. The facility of claim 1, wherein the first module contains: an RNA-based drug substance; and at least one of an LNP -based drug product and a lipoplex-based drug product.
3. 3. The facility of claim 1, wherein each of the first module and the second module comprises a Grade C Clean Room area of from about 80 square meters to about 120 square meters.
4. 4. The facility of claim 1, wherein the second module comprises a first machine for debagging, a second machine for denesting, a third machine for filling and a fourth machine for capping and crimping.
5. 5. The facility of claim 4, wherein the second module further comprises at least one conduit supplying laminar Grade A air to an air bathing area, the air bathing area being located in a vicinity of the first machine for debagging is located.
6. 6. The facility of claim 4, wherein the second module further comprises: a first mixing unit for pooling multiple drug products, each drug product of the multiple drug products comprising different RNA, the multiple drug products being used in a single, multivalent vaccine; and a second mixing unit for performing sterile filtration.
7. 7. The facility of claim 4, wherein the second module further comprises at least one of: lyophilization equipment, an autocalve, glass washing machinery, sterilizing misting equipment, glove box testing equipment, and a wall pass through.
8. 8. The facility of claim 4, wherein the second module further comprises at least one conduit supplying nitrogen to the filling machine.
9. 9. The facility of claim 7, wherein the second module comprises sterilizing misting equipment, and wherein the sterilizing misting equipment is configrued to provides a sterilizing mist comprising ionized hydrogen peroxide.
10. 10. The facility of claim 4, wherein the first module comprises a chromatograph comprising at least one of a cellulose chromatograph, a chromatograph configured to remove oligo (dT) primers, and a chromatograph configured to perform hydrophobic interaction chromatography (HIC).
11. 11. The facility of claim 4, wherein the second module comprises multiple sensors comprising: at least one pressure sensor; at least one combined temperature and humidity sensor at least one hydrogen peroxid sensor; at least one ethanol sensor; and at least one oxygen sensor.
12. 12. The facility of claim 1, wherein the first module contains a lipoplex -based drug product comprising lipoplex particles that comprise a phospholipid bilayer structure that encapsulates RNA molecules of the RNA-based drug substance.
13. 13. The facility of claim 1, wherein the first module contains a lipoplex-based drug product comprising lipoplex particles that comprise a cationic lipid or an ionizable aminolipid in a 2: 1 molar ratio with a helper lipid.
14. 14. The facility of claim 1, wherein the first module contains a lipoplex-based drug product comprising lipoplex particles that comprise a particle size in a range from about 250 nm to about 700 nm.
15. 15. The facility of claim 1, wherein the first module contains a lipoplex-based drug product encapsulating the RNA-based drug substance, wherein RNA of the RNA-based drug substance encodes at least one of a carcinoma antigen, a melanoma-associated antigen, a tyrosinase antigen, and a transmembrane phosphatase with tensin homology (TPTE) antigen.
16. 16. 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 subtance 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.
17. 17. The method of claim 16, wherein producing an RNA-based drug substance comprises performing chromatography prior to a TFF step of the at least one tangential flow filtration (TFF) step.
18. 18. The method of claim 16, wherein performing a filling process comprises: bathing a bag holding the RNA-based drug product in laminar Grade A air while a debagging process occurs to remove the bag; and filling the container with the RNA-based drug product using an automated filling machine.
19. 19. The method of claim 16, wherein the lipid-based drug product comprises a lipid nanoparticle (LNP), and wherein producing a lipid-based drug product comprises: performing an LNP formation step comprising impingement jet mixing; performing a tangential flow filtration (TFF) step following the LNP formation step; and performing at least one formulation step following the TFF step.
20. 20. The method of claim 16, wherein the lipid-based drug product comprises a lipoplex particle, and wherein producing a lipid-based drug product comprises: conditioning RNA from the RNA-based drug substance; performing sterile filtration on the conditioned RNA; and performing a lipoplexation step to produce the lipoplex particle.

Description

MODULAR MULTIPLATFORM SYSTEM FOR MRNA DRUG PRODUCTION Cross-Reference to Related Applications [0001] This application claims priority to U.S. Provisional Patent Application No. 63/511,175, filed June 29, 2023, the title of which is “MODULAR DRUG PRODUCTION SYSTEM”; U.S. Provisional Patent Application No. 63/588,670, filed October 6, 2023, the title of which is “MODULAR MULTIPLATFORM SYSTEM FOR MRNA DRUG PRODUCTION”; and U.S. Provisional Patent Application No. 63/614,026, filed December 22, 2023, the title of which is “MODULAR MULTIPLATFORM SYSTEM FOR MRNA DRUG PRODUCTION”, the content of each of which is incorporated herein by reference in its entirety. Background [0002] Nucleic acids represent an important therapeutic modality; lipid nanoparticle technologies have proven to be particularly useful for the delivery of nucleic acid therapeutics, specifically including RNA therapeutics (for example, mRNA therapeutics). The ability to deliver lipid nanoparticles, nucleic acids, and/or drug products resulting therefrom, (as well as other drug products) in a time-sensitive manner is often constrained by drug product (i.e., bulk drug product) manufacturing capacity, as well as the ability to rapidly adapt drug product manufacturing to current needs. Summary [0003] The present disclosure provides technologies relating to modular drug product manufacturing (i.e., bulk and individualized drug production) including mRNA vaccines and therapies, lipid nanoparticle (LNP) compositions, liposomes, lipoplexes, as well as other drug products and delivery modalities. Quickly producing and delivering therapies and/or treatments to patients often involves challenges relating to but not limited to manufacturing capacity, manufacturing flexibility, the overall time required to produce and deliver a drug product to a patient, as well as other considerations. Often, local requirements relating to certification and approval of drugs categorize drug products differently depending on if they are produced within a country or imported from another country. For example, different regulatory approval hurdles may exist for drugs that are produced within a country than those that exist for drugs that are imported. [0004] In one aspect, the present disclosure is directed to a drug production facility that includes: a first module comprising drug substance and drug product (for example, bulk drug product in some embodiments) manufacturing equipment comprising equipment for producing RNA-based drug substance, lipid nanoparticle (LNP)-based drug products and lipoplex-based drug product; and a second module comprising fill and finish process equipment. [0005] In some embodiments, the first module contains: an RNA-based drug substance; and an LNP -based drug product and/or a lipoplex-based drug product. [0006] In some embodiments, each of the first module and the second module comprises a Grade C Clean Room area of from about 80 square meters to about 120 square meters. [0007] In some embodiments, the second module comprises a first machine for debagging, a second machine for denesting, a third machine for filling and a fourth machine for capping and crimping. [0008] In some embodiments, the second module further comprises at least one conduit supplying laminar Grade A air to an air bathing area, the air bathing area being located in a vicinity of the first machine for debagging is located. [0009] In some embodiments, the second module further comprises: a first mixing unit for pooling multiple drug products, each drug product of the multiple drug products comprising different RNA, the multiple drug products being used in a single, multivalent vaccine; and a second mixing unit for performing sterile filtration (i.e., a final sterile filtration). In some embodiments, the contents are mixed and cooled within the second mixing unit, and the weight of the contents is also measured within the second mixing unit. [0010] In some embodiments, the second module further comprises at least one of: lyophilization equipment, an autocalve, washing machinery (i.e., glass and/or metallic component washing machinery), sterilizing misting equipment, glove box testing equipment, and a wall pass through. [0011] In some embodiments, the second module further comprises at least one conduit supplying nitrogen to the filling machine. [0012] In some embodiments, the second module comprises sterilizing misting equipment, and the sterilizing misting equipment is configrued to provides a sterilizing mist comprising ionized hydrogen peroxide. [0013] In some embodiments, the first module comprises a chromatograph (for example, a cellulose chromatograph, a chromatograph that removes oligo (dT) primers, and/or a chromatograph that performs hydrophobic interaction chromatography (HIC)). [0014] In some embodiments, the first module comprises multiple sensors comprising: at least one pressure sensor; at least one combined temperature and humidity sensor at least one hydrogen p