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Solutions for pDNA / mRNA Manufacturing

Plasmid DNA is accepted as a starting material for the production of mRNA or viral vectors such as lentivirus vectors and adeno-associated virus (AAV) vectors.

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ACCELERATING pDNA / mRNA MANUFACTURING

End-to-end manufacturing solutions

With the proven success of mRNA-based vaccines in addressing the Covid-19 pandemic, mRNA technology is at the forefront of transforming the world of medicine, and the biopharma industry has ongoing clinical trials to develop both vaccines and therapies to treat infectious diseases and even cancer. pDNA is a critical raw material and acts as a template for mRNA manufacturing. Although cell-free, the IVT mRNA process workflow is impacted by low process yields and scalability challenges. Repligen technologies are uniquely suited to help overcome these challenges in process development and manufacturing at the commercial scale for pDNA and mRNA.

Challenges
Solutions

Global high demand

  • Scalability and cost effectiveness
  • Accelerate speed to market
  • Shear sensitivity
  • Low productivity and purification yield

Increased pDNA and mRNA yield
Optimized vector production

  • pDNA: Intensify microbial growth for pDNA production with perfusion-based technology
  • Simplify manufacturing process by replacing centrifugation with microfiltration TFF
  • On-line pDNA product purity monitoring (Process Analytical Technology)

Fully scalable Chromatography and TFF equipment designed for low shear and low hold-up volume performance, maximizing product purity and recovery

Product quality 
Product quality and purity

  • pDNA: open circular pDNA removal
  • mRNA: removal of rDNA, dsRNA, RNA fragments,
    non-encapsulated LNPs

Increased pDNA and mRNA quality

  • Fully sterile and closed automated systems with single-use flow paths
  • Pre-packed columns enable purification and process consistency
  • Analytical in-line technology 

Limited process knowledge

  • Limited scale-up process and implementation experience
  • Lack of in-line process monitoring for cell and cellfree platforms

Expert consultation
Hands-on process and implementation approach from recognized Gene Therapy, oncolytic and vaccines industry experts

 

pDNA/mRNA MANUFACTURING TECHNOLOGIES

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XCell ATF® Systems

  • Scalable, single-use cell retention
  • Higher viable cell density and total pDNA titer

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Hollow Fiber Filters

  • Wide range of membrane formats, chemistries and pore sizes
  • Recommended MWCO for TFF1: 10-300 kDa

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SIUS® Gamma Flat Sheet Cassettes

  • Fully assembled, irradiated cassettes for high flux performance and reduced process time
  • Recommended MWCO: 10-300 kDa

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KrosFlo® TFF Systems

  • Automated hollow fiber or flat sheet TFF
  • Ideal for shear-sensitive vectors with low hold-up volume

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OPUS® Pre-packed Columns

  • Broad range covering process development and commercial manufacturing requirements
  • Pack any resin for plasmid and mRNA purification

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KRM™ Chromatography Systems

  • Superior gradient control, higher peak resolution, high yield
  • Ready-to-operate single-use flow path

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FlowVPX® Device

  • In-line PAT monitoring in downstream
  • Applications in pDNA, mRNA and LNP manufacturing

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Fluid Management Solutions

  • State-of-the-art valve and tubing technology
  • Designed-for-purpose transfer and containment assemblies

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ProConnex® Flow Paths

  • Single-use, sterile, configurable flow paths
  • Plug and play fluid management

Repligen technical support Ensures success

Repligen Field Application Specialists (FAS) with expertise in Gene Therapy provide support from consultation to implementation globally.

Consultation

  • Theory
  • Technology fit
  • Experimental plan

Evaluation

  • Demonstration
  • Training
  • Data analysis

Development

  • Optimization
  • Flow Path sizing
  • System sizing

Implementation

  • Scale-up
  • Validation
  • Long-term training plan

Resources

Expand All

Lentiviral vector manufacturing process enchancement utilizing TFDF® technology
by Thomas Williams, Oliver Goodyear, Lee Davies, Carol Knevelman, Michael Bransby, Kyriacos Mitrophanous and James Miskin
Cell and Gene Therapy Insights, April 2020

Gene Therapy Manufacturing
by René Gantier, PhD, Director of Gene Therapy Technologies, Repligen Corporation 

Repligen Corporation
April 2021

AAV Studies Deploying a Closed, Irradiated, Single-use Flat Sheet TFF Device
by David Bianchi, Carl Breuning, Michael LaBreck, Shelly Parra, Mary Jo Wojtusik, Repligen Corporation 
Alex Meola, Michael Mercaldi, Thomas Thiers, Homology, Medicines Inc. 

Repligen Corporation
Homology, Medicines Inc.
July 2020