Skip to Content
Merck
HomeVaccine ManufacturingChoosing the optimal cell culture media for vaccine production

Choosing the optimal cell culture media for vaccine production

Cultured cells are excellent hosts for the propagation of many types of viruses. The ability of cell culture systems to produce large quantities of attenuated viral particles has served as the basis for the production of both human and veterinary vaccines. Traditional methods have relied on the production of viral agents in cells cultured in medium supplemented with serum, most commonly fetal bovine serum (FBS). The animal serum in cell cultures can cause a number of problems. The increased costs of raw materials and post-production processing associated with serum have prompted interest in the development of serum-free media for vaccine production. More recently, the potential for contamination by adventitious agents present in serum has heightened regulatory concerns regarding the use of animal-derived components in media used for pharmaceutical manufacturing. Therefore, we have developed media for vaccine production with reduced levels or completely devoid of animal-derived components. We will also continue our commitment to traditional manufacturing methods by maintaining and expanding the range of basal media for use with serum supplementation and serve as the basis for customization into serum-free formulations.

The ability to genetically engineer viral particles for use as therapeutic agents to treat genetic diseases (i.e., gene therapy) represents an exciting avenue of science and technology. The regulatory concerns regarding the use of animal-derived materials in media used in pharmaceutical manufacturing, particularly for therapeutic injectables, have led to recommendations that all animal-derived components be avoided when therapeutic agents are manufactured. We offer media tailored to the needs of the two most common cell lines used for the propagation of viral particles used in gene therapy. These media are formulated without the use of animal-derived components.

EX-CELL® Serum-free Vaccine Media produces comparable cell density doubling times

EX-CELL® Media is an animal-protein free, serum-free medium developed for long-term cell growth. The cells, in an attachment culture, can be subcultured directly into EX-CELL® Media from serum-supplemented media without adaptation. Cell densities and doubling times achieved under serum-free conditions are comparable to those achieved in a serum-supplemented culture.

Browse EX-CELL® Serum-free Vaccine Media Products

EX-CELL® EBx™ Serum-free Media Maximizes Vaccine Production in EB66® Cell Line

Human and veterinary vaccines have typically been manufactured using chicken eggs and primary chicken embryo fibroblasts (CEFs) (Table 1). These cell substrates pose a number of limitations including risk of insufficient supply, time-consuming processes with inconsistent yields, high costs of manufacture, the potential for allergic responses to egg-components and concerns associated with using bovine sera in CEF cultures.

Human HealthAnimal Health
 AvianSwine, Equine, BovineCat, Dog
Influenza virusInfluenza virusInfluenza virus (swine, equine)Canine distemper virus
Measles virusReovirusEastern equine encephalitis virusCanine parainfluenza virus
Rabies virusFowlpox virusWestern equine encephalitis virus 
Mumps virusWild type & recombinant poxviruses (canary, chicken, pigeon...)Equine encephalomyelitis virus 
Rubella virusEgg drop syndrome virus  
Avian oncolytic viruses (NDV / IBDV...)Newcastle disease virusBovine parainfluenza virus 
Smallpox virus (Lister, Vaccinia...)Infectious bursal desease virusBovine lbaraki virus 
Recombinant poxvirus (ALVAC, MVA, FP...)Avian adenovirus (type I, II & III)Rabies virus 
Tick-borne encephalitis virusPolyoma virus (type I & II)Swine japanese encephalitis virus 
Yellow fever virusHerpes virus (pigeon, turkey, falcon, psittacine...)  
Sindbis virusInfectious bronchitis virus  
Semliki forest virusEncephalomyelitis virus  
Venezuelan EEV virusAnemia virus (chicken...)  
 Marek's disease virus  
Venezuelan EEV virusMarek's disease virus  
 Parvovirus (duck)  
Table 1. Vaccines produced in chicken eggs or chicken embryo fibroblasts (CEFs)

A fully documented stable duck cell line, termed EB66, derived from embryonic stem cells has been established as a superior alternative for the cost-effective manufacturing of vaccines currently produced in CEFs or eggs. EB66 cells maintain genetic stability, are immortal and grow in serum-free media. An added advantage is high-density growth as suspension cells without the need for microcarriers.

The EX-CELL® EBx™ media and supplements are optimized for use with suspension EB66 cells (Valneva SE) to ensure maximum growth and high titer viral vaccine production. High cell viability and high cell density growth in suspension provides the optimal environment for high-titer viral vaccine production. Typical titer values range from 8 to 9 log TCID50/mL, when using EB66 cells grown in EX-CELL® EBx™ medium and infected with modified vaccinia virus Ankara (MVA) in stirred-tank bioreactors.

Accelerate your timelines by ensuring successful runs

  • High-density suspension cultures
  • No microcarriers or detachment factors required
  • Robust, consistent, scalable process
  • Animal-component free, serum-free media optimized for growth and productivity of EB66 cells
  • Efficient replication of a broad range of viruses (influenza, poxvirus, measles, etc.)

Technical Assistance
For EX-CELL® EBx™ media support and information, please contact Technical Service. For EB66 cell line and viral production process development information, please contact Valneva SE.

Browse EX-CELL® EBx™ Cell Line Media Products

Classic media for vaccine production

Traditionally, viruses for seasonal influenza vaccines have been grown in eggs. Recently, influenza vaccine development has used cell-culture techniques for growing virus in living cells instead of the time-consuming egg-based process.

Browse Classical Media Products

Fetal bovine serum for vaccine production

Fetal bovine serum (FBS) is the most widely used growth supplement for cell culture media because of its high content of embryonic growth promoting factors. When used at appropriate concentrations it supplies many defined and components that have been shown to satisfy specific metabolic requirements for in vitro cell culture.

We continue our commitment to life science researchers with over 30 years of fetal bovine serum production and manufacturing with extensive product testing (Table 2-3). We offer a variety of origins with special treatments and specifications along with a dependable, consistent supply that is ISO certified quality from collection to finished product.

Browse Serum Products

 F2442F6178F4135F039212107CF0643F3018F6765
Sourcebovinebovinebovinebovinebovinebovinebovinebovine
CountryUSAUSAUSAUSAUSAUSAUSAUSA
Sterility
Performance
Cloning Assay
Virus (raw material)
Mycoplasma
Bacteriophage
Endotoxin (EU/mL)≤10≤25≤10≤10≤10≤10≤10≤10
Hemoglobin (mg%)≤20≤25≤20≤20≤20≤20≤20≤20
Total Protein (g%)3.0-4.53.0-4.53.0-4.53.0-4.53.0-4.33.0-4.53.0-4.53.0-4.5
Electrophorectic Pattern
IgG
Hormone Testing
pH at RT6.7-8.06.7-8.06.7-8.06.7-8.06.8-8.16.7-8.06.7-8.06.7-8.0
Osmolality (mOsm/Kg H2O)260-340260-340260-340260-340280-330260-340260-340260-340
Chemical Analysis
Tetracyline




Table 2.Product testing for Fetal Bovine Sera (USA Origin Products)
✓ – Indicates testing is performed and product meets specification.
• – Test is not performed. a – Available in Europe only. Please check with your local supplier regarding availability
F7524aF9665aF1051F9423b12003C12007C12203C12306CF0926
SourceBovineBovineBovineBovineBovineBovineBovineBovineBovine
CountryNot of US Origin
Not of US OriginCanada
AustraliaAustraliaAustraliaNew Zealand
USDA Approved
USDA Approved
Sterility
Performance
Cloning Assay
Virus (raw material)
Mycoplasma
Bacteriophage
Endotoxin (EU/mL)≤10≤10≤10≤10≤10≤10≤10≤10≤10
Hemoglobin (mg%)≤20≤20≤20≤20≤25≤25≤25≤25≤25
Total Protein (g%)3.0-4.53.0-4.53.0-4.53.0-4.53.0-4.53.0-4.53.0-4.53.0-4.53.0-4.5
Electrophoretic Pattern
lgG
Hormone Testing
pH at RT
6.7-8.06.7-8.06.7-8.06.7-8.06.8-8.16.8-8.16.8-8.16.8-8.16.8-8.1
Osmolality (mOsm/Kg,H2O)260-340260-340260-340260-340260-330260-330260-330260-330260-330
Chemical Analysis
Tetracycline
Table 3.Product testing for Fetal Bovine Sera (Non-USA Origin Products)
✓ – Indicates testing is performed and product meets specification.
• – Test is not performed.
a – Available in Europe only. Please check with your local supplier regarding availability.
b – Available in Japan only.
Sign In To Continue

To continue reading please sign in or create an account.

Don't Have An Account?