1Emerging Infectious Disease Vaccines Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea
2College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea
© 2022 Korea Disease Control and Prevention Agency.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Ethics Approval
Not applicable.
Conflicts of Interest
The authors have no conflicts of interest to declare.
Funding
None.
Availability of Data
All data generated or analyzed during this study are included in this published article. Other data may be requested from the corresponding author.
Authors’ Contributions
Conceptualization: JHJ, JTH; Data curation: NL, SHK, SC, MY, JS, EL, SS, JHK; Writing-original draft: JHJ, NL, HJO; Writing-review & editing: JTH, HJO.
Available from regulatory authority websites as of October 2021 (sources: FDA, https://www.fda.gov/emergency-preparedness-and-response/counterterrorism-and-emerging-threats/coronavirus-disease-2019-covid-19; EMA, https://www.ema.europa.eu/en; PMDA, https://www.pmda.go.jp/english/about-pmda/0002.html; Health Canada, https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines.html; Swissmedic, https://www.swissmedic.ch/swissmedic/en/home.html).
COVID-19, coronavirus disease 2019; ICH, International Council for Harmonization; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; FDA, Food and Drug Administration; MA, marketing authorization; EUA, emergency use authorization; EC, European Commission; CMA, conditional marketing authorization; MHLW, Ministry of Health, Labour and Welfare; PMDA, Pharmaceuticals and Medical Devices Agency; SAFE, special approval for emergency; HC, Health Canada; ISAD IO, interim order pathway for COVID-19-related drugs and vaccines; TPA, temporary authorization; -, unauthorized or unapproved.
COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Available from Ministry of Food and Drug Safety website (source: https://nedrug.mfds.go.kr).
COVID-19, coronavirus disease 2019.
Data as of December 3, 2021 (source: https://www.who.int).
Category |
United States (USP) |
Europe (EDQM) |
Korea (MFDS) |
Japan (NIID)a) |
|
---|---|---|---|---|---|
Item | Attribute | Possible test methods | |||
Identity | Sequence confirmation | DNA extraction & sequencing (USP 1125, 1126) restriction analysis (USP 1129, 1126) | Immunochemical methods (EP 2.7.1), NAT (EP 2.6.21), LC (EP 2.2.29) | Immunochemical methods. NAT, LC | Suitable methods |
Vector detection | qPCR, ddPCR, RT-PCR (USP 1125, 1126, 1127), ELISA (USP 1103) | ||||
Purity | Vector aggregates | Light-scattering (USP 1430.2, 1430.3, 1430.5, 1430.6, 1430.7), SEC-MALS (USP 621, 1430.1) | Light-scattering | Light-scattering | - |
Potency | Infectious vector titer | Plaque assays (USP 111, 1235, 1237), CCID50, cell-based qPCR (USP 1032, 1033, 1034) | Plaque assays or CCID50 assay by immunostaining, qPCR, flowcytometry/FACS, fluorescent focus assay | Plaque assays or CCID50 assay by immunostaining, qPCR, flowcytometry, fluorescent focus assay | Immunostaining |
Transgene expression | Western blot (USP 1104), ELISA (USP 1103), LC-MS (USP 621, 736, 1736), RP-HPLC (USP 621) | Immunochemical assay (EP 2.7.1), biochemical assay, flow cytometry (EP 2.7.24) | Immunochemical assay, biochemical assay, flow cytometry | - | |
Quantity | Virus particle (vector concentration) | Light-scattering & DLS (USP 1430.2, 1430.6), CZE (USP 1053), qPCR (USP 1125, 1126, 1127) | qPCR (EP 2.6.21) | qPCR | LC |
Appearance | Compendial test | USP 1, 790 | EP 2.7.1, 2.6.21, 2.2.29 | Visual observation | Criteria specified |
pH | Compendial test | USP 791 | EP 2.2.3 | KP general test | JP general test |
Container content for injections (includes extractable volume) | Compendial test | USP 697 | EP 2.9.17 | KP general test | - |
Sterility | Compendial test | USP 71 | EP 2.6.1 | KP general test | JP general test |
Endotoxin | Compendial test | USP 85 | EP 2.6.14 | KP general test | JP general test |
Osmolality | Compendial test | USP 785 | EP 2.2.35 | KP general test | - |
USP, United States Pharmacopoeia; EDQM, European Medicines Quality Committee; MFDS, Ministry of Food and Drug Safety; NIID, National Institute of Infectious Diseases; EP, European Pharmacopoeia; NAT, nucleic acid test; LC, liquid chromatography; qPCR, quantitative polymerase chain reaction; ddPCR, droplet digital PCR; RT-PCR, reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay; SEC, size exclusion chromatography; MALS, multi-angle light-scattering; CCID50, cell culture infectious dose 50%; FACS, fluorescence-activated cell sorting; MS, mass spectrometry; DLS, dynamic light-scattering; CZE, capillary zone electrophoresis; RP, reverse phase; HPLC, high-performance liquid chromatography; KP, The Korean Pharmacopoeia; JP, Japanese Pharmacopoeia; -, not applicable.
a)Chimpanzee adenoviral vector vaccine only.
Platform | Viral vector vaccines |
mRNA vaccines |
||||||
---|---|---|---|---|---|---|---|---|
ChAdOx1-SARS-CoV-2 vaccine |
Ad26.COV2.S vaccine |
|||||||
Developer | AstraZeneca/Oxford |
Janssen |
Pfizer-BioNTech |
Moderna |
||||
Product information | Name | Approval/date | Name | Approval/date | Name | Approval/date | Name | Approval/date |
Authority | ||||||||
United States, FDA | - | - | COVID-19 vaccine Janssen | EUA/February 27, 2021 | Comirnaty (COVID-19 vaccine, mRNA) | MA/August 23, 2021 (EUA/December 11, 2020) | Moderna COVID-19 vaccine | EUA/December 18, 2020 |
EC, EMA | Vaxzevria (previously AstraZeneca COVID-19 vaccine) | CMA/January 29, 2021 | COVID-19 vaccine Janssen | CMA/March 11, 2021 | Comirnaty | CMA/December 21, 2020 | Spikevax (previously Moderna COVID-19 vaccine) | CMA/January 6, 2021 |
Japan, MHLW/PMDA | Vaxzevria | SAFE/May 21, 2021 | - | - | Comirnaty | SAFE/February 14, 2021 | COVID-19 Moderna | SAFE/May 21, 2021 |
Canada, HC | Vaxzevira COVID-19 vaccine | ISAD IO/February 26, 2021 | Janssen (Johnson & Johnson) COVID-19 vaccine | ISAD IO/March 5, 2021 | Comirnaty COVID-19 vaccine | MA/September 16, 2021 (ISAD IO/December 9, 2020) | Spikevax COVID-19 vaccine | MA/September 16, 2021 (ISAD IO/December 23, 2020) |
Switzerland, Swissmedic | - | - | Janssen COVID-19 vaccine | TPA/March 22, 2021 | Comirnaty | TPA/December 19, 2020 | Spikevax | TPA/January 12, 2021 |
No. | License holder | Product | Approval date (manufacture/import) | Platform |
---|---|---|---|---|
1 | AstraZeneca Korea Co. Ltd. | Vaxzevria injection COVID-19 vaccine (SARS-CoV-2 viral vector vaccine) | February 10, 2021 (manufacture) | Viral vector vaccine |
May 21, 2021(import) | ||||
2 | Pfizer Pharmaceuticals Korea Ltd. | Comirnaty injection (tozinameran) (SARS-CoV-2 mRNA vaccine) | March 5, 2021 (import) | mRNA vaccine |
3 | Janssen Korea Ltd. | COVID-19 vaccine Janssen injection (SARS-CoV-2 viral vector vaccine) | April 7, 2021 (import) | Viral vector vaccine |
4 | Green Cross Corp. | Moderna Spikevax injection (SARS-CoV-2 mRNA vaccine) | May 21, 2021 (import) | mRNA vaccine |
Platform | n (%) |
---|---|
Protein subunit | 47 (34.8) |
Viral vector (non-replicating) | 20 (14.8) |
DNA | 15 (11.1) |
Inactivated virus | 18 (13.3) |
RNA | 21 (15.6) |
Viral vector (replicating) | 2 (1.5) |
Virus-like particle | 6 (4.4) |
Virus-like particle+antigen presenting cell | 2 (1.5) |
Live-attenuated virus | 2 (1.5) |
Viral vector (non-replicating)+antigen presenting cell | 1 (0.7) |
Bacterial antigen-spore expression vector | 1 (0.7) |
Category |
United States (USP) |
Europe (EDQM) |
Korea (MFDS) |
Japan (NIID) |
|
---|---|---|---|---|---|
Item | Attribute | Possible test methods | |||
Identity | Sequence confirmation | DNA extraction & sequencing (USP 1125, 1126) restriction analysis (USP 1129, 1126) | Immunochemical methods (EP 2.7.1), NAT (EP 2.6.21), LC (EP 2.2.29) | Immunochemical methods. NAT, LC | Suitable methods |
Vector detection | qPCR, ddPCR, RT-PCR (USP 1125, 1126, 1127), ELISA (USP 1103) | ||||
Purity | Vector aggregates | Light-scattering (USP 1430.2, 1430.3, 1430.5, 1430.6, 1430.7), SEC-MALS (USP 621, 1430.1) | Light-scattering | Light-scattering | - |
Potency | Infectious vector titer | Plaque assays (USP 111, 1235, 1237), CCID50, cell-based qPCR (USP 1032, 1033, 1034) | Plaque assays or CCID50 assay by immunostaining, qPCR, flowcytometry/FACS, fluorescent focus assay | Plaque assays or CCID50 assay by immunostaining, qPCR, flowcytometry, fluorescent focus assay | Immunostaining |
Transgene expression | Western blot (USP 1104), ELISA (USP 1103), LC-MS (USP 621, 736, 1736), RP-HPLC (USP 621) | Immunochemical assay (EP 2.7.1), biochemical assay, flow cytometry (EP 2.7.24) | Immunochemical assay, biochemical assay, flow cytometry | - | |
Quantity | Virus particle (vector concentration) | Light-scattering & DLS (USP 1430.2, 1430.6), CZE (USP 1053), qPCR (USP 1125, 1126, 1127) | qPCR (EP 2.6.21) | qPCR | LC |
Appearance | Compendial test | USP 1, 790 | EP 2.7.1, 2.6.21, 2.2.29 | Visual observation | Criteria specified |
pH | Compendial test | USP 791 | EP 2.2.3 | KP general test | JP general test |
Container content for injections (includes extractable volume) | Compendial test | USP 697 | EP 2.9.17 | KP general test | - |
Sterility | Compendial test | USP 71 | EP 2.6.1 | KP general test | JP general test |
Endotoxin | Compendial test | USP 85 | EP 2.6.14 | KP general test | JP general test |
Osmolality | Compendial test | USP 785 | EP 2.2.35 | KP general test | - |
Test item | Test methods | |
---|---|---|
General | Appearance | Confirm color, shape formulation, etc. by visual observation |
Container content for injections | Compendial test such as KP general test 65 | |
pH | Compendial test such as KP general test 76 | |
Product- specific | Quantity | Vector concentration (virus particles) such as qPCR, liquid chromatography, etc. |
Identity | Identification of vector including genetic insert such as liquid chromatography, qPCR and gel electrophoresis system, etc. | |
Potency | Determination of transgene expression by qPCR, ELISA, immunostaining, etc. | |
Purity | Determination of vector aggregation such as liquid chromatography, light-scattering tests | |
Safety | Sterility | Compendial test such as KP general test 12 |
Endotoxin | Compendial test such as KP general test 40 |
NRA/NCL | EMA (OMCL) | Australia (TGA) | Korea (MFDS) |
---|---|---|---|
Test items | Appearance, potency, identity (potency may serve as an identity test) | Composition and strength, purity and integrity, endotoxin | Appearance, pH, quantity, identity, potency, purity, sterility, endotoxin, container content for injection |
Category | Description |
---|---|
1. General | a. Information about the product that has been applied for lot release |
1) Name of applicant, name of representative, and address | |
2) Name of the preparation pursuant to the MRBP (MFDS Notification) | |
3) Product name, lot number, manufacturing date, expiry date, period of usage, packaging unit, storage | |
4) Amount that has been applied for national lot release | |
b. Summary on manufacturing information | |
1) Lot number of the raw materials (master cell strains, working cell strains/virus strains), material (master cell line/virus strain, production cell line/virus strain), manufacturing date, etc. | |
2) Bulk, lot number of the final bulk, manufacturing date and manufacturer | |
3) Lot number of final product, manufacturing date, manufacturer, total amount of production, and bottling date | |
2. Raw materials | With regard to the raw materials, testing items, methods, results, detailed information related to the manufacturing, etc. must be included. For cell strains and virus strains, information on the passage history, number of passages, etc. must be included |
3. Bulk | a. Information about half-finished products (intermediates) that are produced during the manufacturing of bulk, name, lot number, manufacturing date, manufacturer, storage conditions (temperature and container), period of storage, amount of production, etc. |
b. Information about bulk, lot number, manufacturing date, manufacturer, storage conditions (temperature and container), period of storage, amount of production, major production methods, etc. | |
c. Information about quality control, information related to the testing items, methods, specifications, period, results, etc. of a test performed according to the quality control manual and approval items of a bulk and materials used for producing the bulk | |
4. Final bulk | a. Information about the material used for producing the final bulk, corresponding material’s ingredient name, lot number, added amount, etc. |
b. Information about the final bulk, lot number, manufacturing date, manufacturer, storage conditions (temperature and container), period of storage, amount of production, etc. | |
c. Information about quality control, testing items, methods, specifications, period, results, etc. of a test conducted according to the quality control manual and approval items of a final bulk | |
5. Final product | a. Information about the drug product, lot number, manufacturer, specification of a container, filling amount, bottling date, manufacturing date, total amount of production, storage, expiration date (shelf life), etc. |
b. Information about quality control, testing items, methods, specifications, period, results, etc. of a test conducted according to the quality control manual and approval items of a final product | |
c. For imported drug products, information that is recorded additionally by an importer, lot number, manufacturer, manufacturing date, date of customs clearance, imported amount, storage method, expiry date (shelf life) in addition to the testing items, methods, specifications, period, results, etc. of a test conducted by the importing party should be included. | |
d. If attached reconstitution solution is included, regarding information about manufacturer, lot number, manufacturing date, expiration date, specifications, and test results |
Available from regulatory authority websites as of October 2021 (sources: FDA, COVID-19, coronavirus disease 2019; ICH, International Council for Harmonization; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; FDA, Food and Drug Administration; MA, marketing authorization; EUA, emergency use authorization; EC, European Commission; CMA, conditional marketing authorization; MHLW, Ministry of Health, Labour and Welfare; PMDA, Pharmaceuticals and Medical Devices Agency; SAFE, special approval for emergency; HC, Health Canada; ISAD IO, interim order pathway for COVID-19-related drugs and vaccines; TPA, temporary authorization; -, unauthorized or unapproved.
COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Available from Ministry of Food and Drug Safety website (source:
COVID-19, coronavirus disease 2019. Data as of December 3, 2021 (source:
USP, United States Pharmacopoeia; EDQM, European Medicines Quality Committee; MFDS, Ministry of Food and Drug Safety; NIID, National Institute of Infectious Diseases; EP, European Pharmacopoeia; NAT, nucleic acid test; LC, liquid chromatography; qPCR, quantitative polymerase chain reaction; ddPCR, droplet digital PCR; RT-PCR, reverse transcription PCR; ELISA, enzyme-linked immunosorbent assay; SEC, size exclusion chromatography; MALS, multi-angle light-scattering; CCID50, cell culture infectious dose 50%; FACS, fluorescence-activated cell sorting; MS, mass spectrometry; DLS, dynamic light-scattering; CZE, capillary zone electrophoresis; RP, reverse phase; HPLC, high-performance liquid chromatography; KP, The Korean Pharmacopoeia; JP, Japanese Pharmacopoeia; -, not applicable. Chimpanzee adenoviral vector vaccine only.
KP, The Korean Pharmacopoeia; qPCR, quantitative polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay.
NRA, National Regulatory Authority; NCL, National Control Laboratory; EMA, European Medicines Agency; OMCL, European Network of Official Medicines Control Laboratories; TGA, Therapeutic Goods Administration; MFDS, Ministry of Food and Drug Safety.
MRBP, Minimum Requirements for Biological Products; MFDS, Ministry of Food and Drug Safety.