Gene Therapy Viral Vector Manufacturing Services

As a trusted viral vector CDMO, we understand there is no single production strategy that works best for all CGMP viral vector manufacturing projects. We offer the flexibility of multiple production methods and the expert knowledge to help you decide which process will best meet your needs. If you’re not ready for CGMP viral vector manufacturing, please see our research-grade viral vector packaging services for more information.

We have the experience and dedication to quality required to scale up your viral vector gene therapy project into a patient-ready product. Explore our range of viral vector production platforms:

Viral Vector Production Platforms

  • Viral Vector Manufacturing Platforms: Adeno-Associate Virus (AAV)

     

       
    Production Cell Lines
    CGMP AAV Viral Vector Manufacturing Technology Key Features Adherent (CellSTACK; iCELLis) Suspension
    (50-500 L bioreactors)
    Helper-free triple transfection Fastest turnaround time HEK293, 293T HEK293-s, 293T-s
    Helper virus Easily scales to commercial quantities HEK293, 293T HEK293-s, 293T-s
    Baculovirus Highest producing platform   Sf9

    Need to discuss your upcoming AAV viral vector manufacturing needs? Contact us.

  • Viral Vector Manufacturing Platforms: Lentivirus

     

       
    Production Cell Lines
    CGMP Lentivirus Viral Vector Manufacturing Technology Description Adherent (CellSTACK; iCELLis) Suspension
    (50-100 L bioreactors)
    2nd Generation Three plasmids, higher yield HEK293, 293T HEK293-s, 293T-s
    3rd Generation Four plasmids, increased safety HEK293, 293T HEK293-s, 293T-s

    Need to discuss your upcoming lentivirus viral vector manufacturing needs? Contact us.

    If you’re not ready for CGMP viral vector manufacturing, please see our research grade lentivirus packaging services for more information.

  • Viral Vector Manufacturing Platforms: Adenovirus

     

       
    Production Cell Lines
    GMP Adenovirus Viral Vector Manufacturing Technology Description Adherent (CellSTACK; iCELLis) Suspension
    (50-500 L bioreactors)
    Client-supplied plasmid We perform all the steps to generate the adenovirus seed stock before producing GMP adenovirus HEK293, 293T HEK293-s, 293T-s
    Client-supplied adenovirus We produce GMP adenovirus using the provided virus HEK293, 293T HEK293-s, 293T-s

    Need to discuss your upcoming adenovirus viral vector manufacturing needs? Contact us.

    If you’re not ready for CGMP viral vector manufacturing, please see our research grade adenovirus packaging services for more information.

  • Viral Vector Manufacturing Platforms: Retrovirus

     

    GMP Retrovirus Viral Vector Manufacturing Technology Description Advantages Cell Lines
    Transient transfection Two plasmid (2nd generation) or three plasmid (3rd generation) Rapid implementation, maximum flexibility

    HEK293, 293T (adherent) or HEK293-s, 293T-s (suspension)

    Stably-transduced producer cell lines Producer cell plus transfer plasmid Maximum scalability potential

    Client-provided

    Need to discuss your upcoming retrovirus viral vector manufacturing needs? Contact us.

  • Custom Virus Manufacturing Platforms

     

    Custom Virus Project Example Viruses Application
    Tropical Infections Dengue, Ebola, etc. Vaccine Studies
    Sexually Transmitted Infections HPV, HIV, etc. Vaccine Studies
    Gene Therapy AAV, lentivirus, helper-dependent adenovirus, retrovirus, HSV, Poliovirus, VSV, etc. Expression Vectors
    Oncolytic Viruses Adenovirus, HSV, Vaccinia, Reovirus, Measles, NDV, etc. Cancer Therapeutics

    Gene Therapy Vectors and Oncolytic Viruses

    We recognize that a great variety of gene therapy vectors exist, each with unique advantages and potential applications. As examples, vectors based on HSV, poxviruses, and helper-dependent “gutless” adenoviruses offer the potential for large payload capacities beyond what can be attained by AAV or lentiviral vectors. Some viruses have a natural tropism to certain target tissues (such as the neural tropism of poliovirus or HSV) that make them well-suited for certain disease applications. Oncolytic viruses have either a naturally occurring or engineered ability to selectively replicate in and destroy cancer cells and continue to show promise in pre-clinical and clinical studies, particularly in combination with immunomodulatory drugs. Regardless of which platform you need, we welcome the opportunity to provide custom gene therapy viral vector manufacturing services to advance your CGMP project.

    Need to discuss your upcoming viral vector production needs? Contact us.

Choosing a Production Cell Line

The production cell line is a key component of any CGMP manufacturing campaign for a gene therapy vector. The characteristics of the selected cell line (origin/derivation, doubling time, permissiveness for viral infection and replication) determine the efficiency of viral productivity, while the growth conditions determine the requisite downstream processing methods and release tests for the final drug product.

We have developed a set of proprietary cell lines for virus manufacturing in either suspension or adherent culture. The efficiency with which our proprietary cell lines can propagate a virus allows us to generate high yields of your product with the highest levels of purity.

  • Suspension and adherent cells (HEK293, 293T)
  • Fully qualified and released CGMP MCBs
  • High productivity

Viral Vector CGMP Process Development

The development of an efficient manufacturing process is critical in order to ensure that the large amount of material needed for clinical trials is produced efficiently, safely, and consistently. Our Process Development services help achieve consistent CGMP production and reduce costs for both clients and patients. Starting your project with our CGMP Process Development team ensures that your project meets FDA regulatory requirements with reduced costs going forward and high quality standards.

  • Explore Our Viral Vector Process Development Services
    Production Stage Purpose Available Services
    Upstream Optimization of parameters for scale-up and production, including culture and transfection conditions
    • Process optimization using scale-down models (iCELLis® Nano, T-flask, shake flask, 10L stir tank reactor)
    • Cell line engineering and adaptation
    • Media/feed screening and optimization
    • Transfection/infection optimization
    • High-density cell culture and transfection/infection
    • Harvest, lysis, and clarification
    Downstream Optimization of product recovery, purification, and formulation procedures
    • Column and membrane chromatography (affinity, ion exchange, size exclusion, mixed-mode, automated chromatography platforms)
    • Bioprocess filtration (tangential flow, hollow fiber, depth filtration)
    • Ultracentrifugation
    CGMP QC Services Ensures safety, potency, purity, and identity of final CGMP drug product
    • Formulation studies
    • Vial compatibility studies
    • Viral clearance studies
    • Viral stability studies
    • Long-term stability studies
    • Assay development

    1. The upstream phase concerns optimization of all procedures involved in scale-up and production of the material.
    2. The downstream phase involves optimization of procedures related to recovery, purification, and concentration of the final product.
    3. The final phase of process development includes assay development related to product safety, potency, purity, and identity.

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Frequently Asked Questions (FAQs) for Gene Therapy Viral Vector Manufacturing

  • How do retroviruses and lentiviruses differ?

    Retroviruses are a family of viruses characterized by their ability to reverse transcribe their RNA genomes into DNA, which can then stably integrate into the host cell genome. Due to their ability to permanently modify the genetic makeup of a target cell, retroviruses attracted attention early on and became the first viral vectors to be used in gene therapy clinical trials. Importantly, retroviruses can only transduce dividing cells, whereas lentiviruses can transduce both dividing and non-dividing cells. Most retrovirus vectors are based on murine leukemia virus (MLV), a simple or gamma-retrovirus (as opposed to lentiviruses, which are more complex members of the retrovirus family). Retroviruses have a greater variety of stable producer cell lines available than do lentiviruses, due to their longer history of use, more simplistic genomes, and because some lentivirus accessory genes are toxic to mammalian cells.

  • Why include an engineering run?

    The engineering run is a vital part of any CGMP viral vector manufacturing campaign as it allows for the detection of any unforeseen issues that could impact CGMP production. The engineering run uses the exact same procedure as the GMP run, but is not performed in the CGMP facility (i.e., no regulated air supply and not subject to QA oversight). This run allows for the confirmation that all of the campaign-specific processes will be successful and that the expected viral titer will be obtained. Material produced during the engineering run can be used for in vitro or in vivo testing (or toxicity studies) but cannot be used in patients.

  • Is recombinant lentivirus/retrovirus safe to use?

    We primarily use a 3rd generation lentivirus/retrovirus packaging system, in which the lentivirus/retrovirus genome is distributed among three plasmids. This greatly reduces the likelihood of recombination events that could allow generation of replication-competent retrovirus. Over the long history of lentivirus/retrovirus clinical trials, it has demonstrated a predominantly safe track record, although some insertional mutagenesis events have occurred in a limited number of patients. However, the continued development of self-inactivating vectors and other measures taken to reduce risk have resulted in increasingly safe lentiviral/retroviral vectors.

  • What is the typical yield for CGMP viral vector production?

    Because viral vector titer is highly sensitive to the size of the viral genome, the resulting viral vector manufacturing yield will vary depending on the size of the desired insert. Please contact us for more information about what yield may be obtainable with your insert.