Production of vaccine industrially explained in 5 min. Factors under consideration and storage. Types of vaccine produced all under one presentation.

1. Viral Vaccine
Production
SOURABH SANTOSH GURAV
MTECH BIOPROCESS TECHNOLOGY
INSTITUTE OF CHEMICAL TECHNOLOGY

2. IMPORTANT AREAS FOR A VIRAL
VACCINE
• Five important areas for a viral vaccine are -
(1) the choice of the cell substrate
(2) the choice of the virus construct
(3) bioreactor technology
(4) purification
(5) final product stabilization.

3. Cell Substrates
• Human diploid cell lines: Medical Research Council-5 (MRC-
5) & Wistar Institute-38 (WI-38)
• Continuous cell lines : Vero and Madin Darby Canine Kidney
(MDCK)
• recombinant “designer” cell lines: PER.C6 and CAP
• plant-based recombinant protein production (Not
commercial)

4. VACCINE TYPE REMARK EXAMPLES
• Inactivated Vaccine or
killed vaccine
Pathogens that have been grown in culture and
then lose disease producing capacity
Hepatitis A, whole cell
Pertussis
• live vaccines Pathogens are still alive but are almost attenuated,
that is, weakened
Oral Polio Vaccine,
Rotavirus, Tuberculosis
(BCG) etc
• Subunit vaccine Contains a fragment of the pathogen and elicits an
appropriate immune response
• Diphteria, acellular
Pertussis, Subunit influenza
• Virus - like - particle
Vaccine
Molecules that mimic viruses but are not
infectious
Human Papilloma Virus
(HPV)
• Viral Vector Vaccine Uses a chemically weakened virus to transport
pieces of the pathogen
• DNA , RNA Vaccine Uses a man-made copy of a natural chemical
called messenger RNA (m RNA) or DNA to produce
an immune response

5. Bioreactor Technology
• Attachment-dependent modalities such as t-flasks, cell factories,
and roller bottles
• At industrial scale –
i. Small spheres (microcarriers) kept in suspension
ii. 6000L scale
• Single-use bioreactors
i. Facilitates multiproduct manufacturing in facilities and reduces
change-over times between batches

6. Microcarrier Cell System
Hollow fibre Membrane

7. 1.CELL
EXPANSION
2.VIRUS
PROPOGATION
(BIOREACTOR)
3.Removal of cell
debris and large
particles
4.CONCENTRATION
5.Separation of virus
from small molecular
compounds
6.Virus
inactivation
formaldehyde
5.Formulation
Sterile filtration,
mixing with other
strains
typical viral vaccine production process

8. • Harvesting of the virus by centrifugation
and/or filtration
• Purification via chromatograph
• Inactivation as needed with chemical
additives
• Final conditioning with tangential flow
filtration
• Size-exclusion chromatography :purification
of whole virus
• Flow-through chromatography :impurities in
the feed are adsorbed to the resin
Cell Culture Roller Flask System

9. Virus Stabilization
• addition of complex stabilizers and via lyophilization for live
viral vaccines
• enable distribution
• need to supply a separate diluent in addition to the dry
powder
• spray drying have been investigated

10. • spray-drying
mechanism

11. STORAGE
live-virus vaccines :tolerate freezing temperatures and rapidly
deteriorate once defrosted
inactivated vaccines :require stable temperatures of 2-8⁰C