Vaccine Manufacturing

疫苗生产:从研发到生产

世界卫生组织 (WHO) 目前在全球列出170多个项目,这些项目致力于开发可以控制 SARS-nCoV2 的疫苗。30 多种候选疫苗已经进入临床的不同阶段,目前正在接受测试。开发新疫苗具有挑战性,不同的方法需要使用不同的实验室设备。

以下所示方法和研究设备旨在助力抗原分子研究应用。BioFlo系列生物工艺控制系统具有全套验证文件,符合cGMP生产环境的要求。

经典方法

亚单位/抗原 
在鉴定出潜在的亚单位/抗原候选物之后,第一步是培养重组细菌或酵母以生产候选化合物。随后对候选化合物进行筛选。因此,小规模的优化和精确的培养条件至关重要,以确保可成功放大为大规模生产。

基于病毒 
基于病毒设计的疫苗依赖于弱化或灭活的病毒,它们不再具有传染性,但会激发免疫反应。为了生产起始原料,通过诱导特定的突变来弱化病毒,或者在鸡胚或人体细胞中进行多次传代培养,直到自然发生突变,使病毒毒力降低至不易引发疾病。另一种方法是以化学或热介导进行病毒灭活。   

核酸疫苗
尤其 mRNA 疫苗是开展临床测试的首批候选药物之一,因为它们的开发和生产时间比传统疫苗短。  免疫机理是通过将一种基于编码病毒抗原的信使RNA序列包被到脂质体中激发被侵染的细胞产生免疫反应。

Produce Starting Material

Having the right starting material is the first step to develop a new vaccine, e.g., plasmid construction and amplification successfully. The quality of the expression constructs has a significant impact on the growth- and production rate throughout the process, and once found to be efficient, plasmids must be amplified on a larger scale.

Eporator®

  • Faster sample handling – for the quicker transformation of yeast and bacterial cells
  • Fast, freely programmable softkeys for saving and accessing
    the two most frequently used parameters
  • Compact, space-saving design

More about Temperature Control and Mixing


Tubes and Deepwell Plates

  • Manufactured without the use of slip agents, plasticizers, and biocides – substances that have been shown to leach from plastic consumables into the sample and negatively affect bio-assay results
  • g-Safe® Tubes: Exceptional centrifugation stability up to 30,000 x g prevents sample loss due to tube breakage and provides extra safety when working with hazardous samples
  • Deepwell plates are ideal for cultivation and long-term storage. OptiTrack® matrix: 30 % faster sample identification and fewer pipetting errors via high-contrast alphanumeric labeling

More about Tubes and Deepwell Plates


Thermo mixing devices

  • Heating, mixing and cooling in all standard vessel and plate formats from 5 µL to 50 mL for different ideal incubations
  • Excellent mixing performance due to unique 2D Mix-Control technology with anti-spill technology prevents lid wetting and cross-contamination
  • Reliable prevention of condensate formation with the new ThermoTop® (condens.protect®)

More about Thermo mixing


Shakers

  • Optimized vessel capacity for high yield plasmid production (e.g., 20x 1L Erlenmeyer or 13x 2,5L UltraYield® on Universal Platform)
  • High load/speed protocols can be run, e.g., in Thomson flasks for high yield plasmid production with 24/7 drive reliability
  • Stackable – up to three units for maximum capacity in minimum space
  • Slide-out platform mechanism — provides easy and effortless access to the sample
  • Spill protected drive and drainable bottom

More about Lab Shakers


Centrifuges

  • Highly ergonomic for extensive and repetitive protocols
  • High capacity rotor for up to 48 samples

More about Centrifugation


Photometers

  • Spin column rotor for easy usage and high performance of DNA extraction kits Photometers
  • UV/Vis spectral range 200 nm to 830 nm to monitor samples and growth
  • Freely selectable wavelengths across the entire UV/Vis spectral range (increment: 1 nm)
  • Compatible with microliter measuring cells and standard cuvettes
  • Temperature-controlled cuvette shaft in the BioSpectrometer® kinetic (20°C to 42°C in 0.1 °C increments)

More about Photometry


Storage and Management

  • Samples can be stored in an Ultra-Low Temperature Freezer
  • Samples can be stored in high-quality Cryo tubes 
  • eLABJournal® and eLABInventory allow for effortless archiving and documentation

Eppendorf CryoCube F570 ULT freezer for storage of lab samplesMore about Sample storage solutions 


Manual Liquid Handling

  • The adjustment option allows you to perfectly adapt the pipette for specific liquids or other external conditions
  • Repetitive dispensing modes decrease the number of movements by allowing the user to fill the tip once and dispense up to 100 times without a refill
  • Automatic Combitip recognition eliminates time-consuming volume calculations
  • Wide dispensing range: 1 µL to 10 mL to cover the required volumes precisely

More about Manual Liquid Handling


Thermocycler

  • Intuitive graphic programming
  • Small footprint and cycler manager software for parallel screening of samples
  • Universal block for ultimate flexibility

More about Thermocycler


Pipettes and Tips

  • The ultralight research was developed according to the strict criteria of the PhysioCare Concept®
  • The adjustment option allows you to perfectly adapt the pipette for specific liquids or other external conditions
  • Large volume range available to cover the required volumes precisely

More about Pipettes


Automation

  •  An established platform for nucleic acid purification and PCR setup
  • Supports kits for magnetic bead cleanup as well as filter plate-based methods (via vacuum)
  • Intuitive software with established methods available

More about Automation Solutions

Screening

Cell lines need to be tested to ensure the most efficient production at the end. This includes testing for the correct insert and analysis of the desired product's quantity and quality in flasks. In production volumes of up to 2,000 L already, a difference in the product of a few µg/mL resulted in a considerable difference in the end. The screening process involves numerous steps more information for candidate screening here.

Pipettes and Tips

  • The ultralight research was developed according to the strict criteria of the PhysioCare Concept
  • The adjustment option allows you to perfectly adapt the pipette for specific liquids or other external conditions
  • Large volume range available to cover the required volumes precisely

More about Pipettes and Tips


Tubes and Deepwell Plates

  • Manufactured without the use of slip agents, plasticizers, and biocides – substances that have been shown to leach from plastic consumables into the sample and negatively affect bio-assay results
  • g-Safe® Tubes: Exceptional centrifugation stability up to 30,000 x g prevents sample loss due to tube breakage and provides extra safety when working with hazardous samples
  • Deepwell plates are ideal for cultivation and long-term storage. OptiTrack® matrix: 30 % faster sample identification and fewer pipetting errors via high-contrast alphanumeric labeling

More about Tubes and Deepwell Plates


Photometers

  • UV/Vis spectral range 200 nm to 830 nm to monitor samples and growth
  • Freely selectable wavelengths across the entire UV/Vis spectral range (increment: 1 nm)
  • Compatible with microliter measuring cells and standard cuvettes
  • Temperature-controlled cuvette shaft in the BioSpectrometer® kinetic (20°C to 42°C in 0.1 °C increments)

More about Photometry


Freezer

  • Samples can be stored in an Ultra-Low Temperature Freezer
  • eLABJournal® and eLABInventory allow for effortless archiving and documentation

More about Freezers


S41i

  • Easy cleaning and disinfection: Seamless chamber, easy disassembling in 40 s, 180 °C disinfection with protocol
  • Full control and easy documentation: Advanced user interface, two front USB-ports, customized tasks and alarms, VisioNize® user management, and connected lab
  • Save money: No internal expendable parts (e.g., fan-associated HEPA filters), significantly reduced gas consumption, up to 25 % more usable space by fanless design and innovative insulation concept and flexibility for the future

More about s41i


Centrifuges

  • Large vessel size range (0,2 ml - 1000 ml) and the capacity to support large screening setups
  • Additional high vessel type versatility (Eppendorf Tubes®, conicals, Corning® flasks, deep-well plates, and more) to support individual screening protocols
  • Precise temperature management with FastTemp Pro® function to guarantee sample safety and maximum temperature accuracy
  • Ergonomic design with special light-weight rotors to ensure user safety and easy handling

More about Centrifugation

Optimize Cultivation Methods

Reagents are expensive; losing a batch due to the systems' faulty equipment or failures can also be very expensive. Choosing the right, high-quality equipment from the start saves time and money. Optimizing all-important growth parameters such as pH, temperature, stirring speed gas supply, and nutrient concentration, to name the most important ones, is best done in small scale parallel bioreactor systems. Parallel bioprocess control systems are well suited for scale-down approaches and offer the possibility of changing individual parameters in several bioreactors at the same time while monitoring and comparing the effect of the changes in parallel.

Storage and Management

  • Samples can be stored at up to -80°C
  • eLABJournal® and eLABInventory allow for effortless archiving and documentation

More about Sample storage solutions


Static incubation of mammalian cells (CellXpert®)

  • Easy cleaning and disinfection: Seamless chamber, easy disassembling in 40 s, 180 °C disinfection with protocol
  • Full control and easy documentation: Advanced user interface, two front USB-ports, customized tasks and alarms, VisioNize user management, and connected lab
  • Save money: No internal expendable parts (e.g., fan-associated HEPA filters), significantly reduced gas consumption, up to 25 % more usable space by fanless design and innovative insulation concept and flexibility for the future

More about CellXpert


CO2 Shaking incubator (S41i)

  • Early process and starting inoculums for bioreactors of mammalian cultures can be prepared in shaking incubators
  • Reproducible growth conditions with trackable performance data ensure high quality and reproducible results throughout the whole process
  • Easy cleaning and reliable contamination prevention with 120 °C disinfection, seamless chamber, and a fanless design
  • Reproducible growth conditions with trackable performance data

More about s41i


Photometers

  • UV/Vis spectral range 200 nm to 830 nm to monitor samples and growth
  • Freely selectable wavelengths across the entire UV/Vis spectral range (increment: 1 nm)
  • Temperature-controlled cuvette shaft in the BioSpectrometer® kinetic (20°C to 42°C in 0.1 °C increments)

More about Photometry


Manual Liquid Handling

  • The adjustment option allows you to perfectly adapt the pipette for specific liquids or other external conditions
  • Repetitive dispensing modes decrease the number of movements by allowing the user to fill the tip once and dispense up to 100 times without a refill
  • Automatic Combitip recognition eliminates time-consuming volume calculations
  • Wide dispensing range: 1 µL to 10 mL to cover the required volumes precisely

More about Manual Liquid Handling


Tubes and Deepwell Plates

  • Manufactured without the use of slip agents, plasticizers, and biocides – substances that have been shown to leach from plastic consumables into the sample and negatively affect bio-assay results
  • g-Safe® Tubes: Exceptional centrifugation stability up to 30,000 x g prevents sample loss due to tube breakage and provides extra safety when working with hazardous samples
  • Deepwell plates are ideal for cultivation and long-term storage. OptiTrack® matrix: 30 % faster sample identification and fewer pipetting errors via high-contrast alphanumeric labeling

More about Tubes and Deepwell Plates


Centrifuges

  • Large vessel size range (0,2 ml - 1000 ml) and capacity support a wide range of test conditions individual protocol requirements
  • Additional high vessel type versatility (Eppendorf Tubes, conicals, Corning flasks, deep-well plates, and more) support individual screening protocols
  • Programmable centrifuges to ensure high protocol reproducibility
  • Ergonomic design with special light-weight rotors to ensure user safety and easy handling

More about Centrifugation


Parallel Bioprocess Control Systems

  • Small scale Parallel bioreactor control systems enable the efficient testing of multiple process parameters at the same time.
  • Testing in small volumes (up to 250 mL) in up to 24 bioreactors in parallel saves valuable resources and time

More about Bioreactor


Monitoring and Control of Process Parameters

  • Powerful software enables optimal process control
  • Use scripting to improve your process further
  • Seamless integration of 3rd party sensors via modern communication protocols such as OPC-UA
  • Integration of external process analytical technologies (PAT)

More about Monitoring Software


Bioreactors and Fermenters

  • Choose between a variety of reusable glass or Single-Use Stirred-tank bioreactors for cell culture or microbial applications
  • With vessel sizes in a range of 0.2 to 40 L, we have the right vessel for your aplications

More about Vessels


Impeller

  • The impeller has a significant impact on the culture. Spin filter and packed-bed impeller are the right choices for the cultivation of anchorage-dependent cells, such as Vero cells, widely used as a platform for viral vaccine production.
  • Choose a Rushton-type impeller if your cells are not sensitive to shear stress, such as bacteria for plasmid production.

More about Impellers


Accessories

Efficient process development for vaccine production relies on the Quality-by-Design (QbD) paradigm, which aims to understand the relation between a process and its product fully. This knowledge is gained by process analytical technology (PAT).

  • With the right selection of sensors, you always have full control over your process

More about Manual Liquid Handling

Optimize Scale-Up Parameters

It is essential to work with bioreactors that are comparable at the bench- and pilot- and production-scale. To ensure successful scale-up from R&D to production, critical scalability related engineering parameters are tested and optimized. Eppendorf systems and bioreactors are designed in a way to ensure seamless scalability from 0.2 – 2000 L.
Critical parameters that are tested and optimized in this step are proportional vessel/impeller geometry, oxygen transfer rate (OTR), impeller power number (Np), and the impeller power consumption per volume (P/V).

Bioprocess controller

  • Compare and analyze different process parameters at different scales ranging from 0.2 – 3.7 L in parallel. (Up to 40 L after future updates)
  • Ready for the digital age: Allows remote monitoring and notifications to keep track of your process.


 

  • Increase your production volume up to 40 L
  • When combined with optional validation documents and the BioCommand® Batch Control Plus software, the BioFlo® 320 is a perfect solution for bench scale cGMP needs

More about Bioprocess Controller


Monitoring and Control of Process Parameters

  • Monitoring and Control of Process Parameters
  • Use scripting to improve your process further
  • Seamless integration of 3rd party sensors via modern communication protocols such as OPC-UA
  • Integration of external process analytical technologies (PAT)

More about Monitoring Software


Bioreactors and Fermenters

  • Choose between a variety of reusable glass or Single-Use Stirred-tank bioreactors for cell culture or microbial applications
  • With vessel sizes in a range of 0.2 to 40 L, we have the right vessel for your aplications

More about Vessels


Impeller

  • The impeller has a significant impact on the culture. Spin filter and packed-bed impeller are the right choices for the cultivation of anchorage-dependent cells, such as Vero cells, widely used as a platform for viral vaccine production.
  • Choose a Rushton-type impeller if your cells are not sensitive to shear stress, such as bacteria for plasmid production.

More about Impellers


Centrifuges

  • Support high vessel capacity to allow a wide range of test conditions
  • Additional high vessel type versatility (Eppendorf Tubes, conicals, Corning flasks, deep-well plates, and more) support individual protocol needs
  • Ergonomic design with special light-weight rotors to ensure user safety and easy handling

More about Centrifugation

Pilot and Production Scale

The production of enough vaccination doses for everyone requires large scale vaccine manufacturing facilities and systems. Validated systems for the production of vaccines in cGMP regulated environments are needed. With bioreactors up to 2,000 L volume, Eppendorf improves human living conditions by supplying equipment to produce a large number of vaccines.

Bioprocess controller

  • Produce vaccines in cGMP regulated environments, if combined with optional validation documents and the BioCommand Batch-Control Plus software.
  • Perfect for Scale-Out approaches: Connect and control up to eight BioFlo 320 control systems with each other

  • Scale up your process up to 2,000 L with the BioFlo control systems
  • The integrated BioFlo control software ensures a consistent user experience among all BioFlo control systems

More about CelliGen® 510


Monitoring and Control of Process Parameters

  • Powerful software enables optimal process control
  • Use scripting to improve your process further
  • Seamless integration of 3rd party sensors via modern communication protocols such as OPC-UA
  • Integration of external process analytical technologies (PAT)

More about Monitoring Software