1. (Gaurav Gupta, Vaccine Technology Centre, Zydus Cadila, India)
CREATIVE IMPLEMENTATION OF NEW TECHNOLOGY PLATFORMS FOR RAPID PRODUCTION AND MANUFACTURING OF VACCINES & ANTIBODIES
(Gaurav Gupta, Vaccine Technology Centre,
Zydus Cadila, India)

2. CONTENTS
Current Global trends in production of vaccines and antibodies
Key targets for new technologies implementation in Vaccines & antibodies
Challenges and future potential in implications

3. CURRENT GLOBAL VACCINE PRODUCTION TRENDS
Cell culture
MRC-5 cells- MMR, Varicella, Rabies
Vero cells- JEV, Rabies, Influenza, Rota, Polio, Dengue
Primary cells- CEF for Mumps, Rabies
Fermentation
E Coli/Yeast culture- Papilloma, Hepatitis B, Malaria
Seed strains (Diphtheria, Pertussis, Tetanus, Hemophilus, Pneumococcal, Meningiococcal)
Egg based
Allantoic route: Influenza
Yolk sac: Rabies
Animal based
Mice brain: JEV, Congo

4. CURRENT GLOBAL ANTIBODY PRODUCTION TRENDS
Cell culture
CHO cells
Hybridoma
PERC.6
HEK293
fermentation
E Coli/yeast - Antibody fragments
Animal immunization
Mice and rabbits
Horse

5. Information technology
KEY TARGETS FOR NEW TECHNOLOGIES IMPLEMENTATION IN VACCINES & ANTIBODIES
Production & testing
GMP facility
Manpower
Documentation
Information technology
Logistics

6. PRODUCTION AND TESTING METHODS

7. PRODUCTION PROCESS FLOW
Production of antigen or antibodies in suitable substrate system
Purification of antigen/antibodies
Formulation, filling and lyophilization
Inprocess and finished product testing & release to Market
Time should be reduced at every step for rapid Manufacturing

8. Rapid Production of antigens/antibodies
1. Adaptation of seed strain/Clone in substrates of quick production
No substrate
E coli
Yeast
mammalian cells
Eggs
Animals

9. Bioreactors- disposable/ reusable
Rapid Production of antigens/antibodies 2. Selection of rapid production platforms:
Cell culture
Bioreactors- disposable/ reusable
Robotic cell culture system
Manual techniques- roller bottles/ cell factories
Fermentation
Fermenters
Shake flask cultures
Egg based
Automatic inoculation, harvesting
Manual techniques
Animal based
Small animals
Large animals

10. Rapid Purification of Antigen/Antibodies
Clarification
Continuous centrifugation
Batch centrifugation
filtration
ultrafiltration
Precipitation
Ammonium Sulphate
PEG
Column chromatography
Ion exchange/Hydrophobic/ affinity
gel filtration
Ultracentrifugation
continuous
batch
sucrose gradient
cesium chloride gradient
Ultrafiltration
hollow fibres
Tangital flow filtration
Diafiltration
dialysis membranes
Filtration
cross flow
depth filtration

11. RAPID FORMULATION, FILLING AND LYOPHILIZATION
Blending in disposable bags
Blending in vessels
Use of animal origin free excipients
use of animal origin excipients
Filling speed
Filling containers
Single type of vial/PFS for single and multiple doses
Different vials/PFS
Lyophilization capacity
Lyophilization cycle
Cycle optimization to reduce cycle time
Packing & release
Automatic visual inspection, labeling & packing
Manual

12. Rapid Testing Methods Carbohydrate Lipid Host cell protein
(Genomics & Proteomics)
Characterization methods
Seed
Drug substance & Drug product
Rapid microbiological tools
Sterility (Bacterial, Mycotic, Mycoplasma & Mycobacteria)
EMP
(cell based, Immunoassays)
Potency methods
In vitro methods
In vivo methods
Biochemical methods
(Kit based)
Carbohydrate
Lipid
Host cell protein
Host cell DNA

13. GMP FACILITY
Installation of Flexible modular facility for quick production as per BSL requirements
Installation of multiproduct facilities
Upgradation with modern instruments for rapid production in existing facilities

14. INFORMATION TECHNOLOGY
Updated softwares for all respective areas in production, quality and regulatory
Access to online global knowledge sharing domains
Introduction of Project management softwares
LOGISTICS
Online purchasing of raw materials
Robotic dispensing of raw materials
Online Inventory management of raw materials and finished products

15. MANPOWER
Training onsite & offsite to Production, QC,QA, engineering & regulatory staff on regular basis for new technologies
DOCUMENTATION:
Paperless Online system of documentation for production, testing and release

16. CHALLENGES IN IMPLICATIONS OF RAPID MANUFACTURING
Evaluation of need-Market demand & process upgradation
Environment concerns due to heavy waste generation
Cost implications for process, facility and registration
Commercial returns & payback period

17. FUTURE POTENTIALS
Promising for launching new product where no better alternative is available for global unmet health problems (Malaria, Dengue, TB,HIV)
High productivity is expected so low cost of production due to efficient infrastructure and organization.
Less manpower dependent therefore high consistency can be expected.
Lesser time to reach Market

18. CONCLUSIONS
Rapid manufacturing tools and technologies are now available for worldwide use in vaccine and antibodies production.
Considering present marketed products, it will be only a mindset question to take forward for execution.
Keeping ourselves updated with new technologies will be the key for execution.
The national regulatory environment has a lot of impact on the success of introduction for new technologies and products in the relevant country and need to be addressed.
For future novel products it will be widely and easily acceptable due to lesser commercial & regulatory challenges.

19. THANKS