Platforms

Broad and extensive expertise

Powered by innovation, we have established expertise across a broad range of cell and gene therapy platforms:

Cell Therapy

Autologous, Allogeneic

Viral Vectors

AAVs,
Lentivirus

mRNA

mRNA drug substance Formulated drug product

Oncolytic Virus

AdV, VSV, HSV, Vaccinia Virus

Plasmid

Supercoiled plasmid
Linear Plasmid
DNA Vaccine

Cell Therapy

We support both autologous and allogeneic cell therapy

Today, cell therapy is one of the most successful applications of advanced medicine. Porton Advanced offers both autologous and allogeneic cell therapy platforms.

In autologous cell therapy,
T cells are collected from the individual patient. This includes CAR-T, TCR-T, TIL, etc.

In allogeneic cell therapy,
Cells are obtained from healthy donor pools, such as UCAR-T, NK, stem cells, IPSCs, etc.

We offer our customers integrated support, including process development, analytical development, cGMP manufacturing, research support, testing services, and regulatory assistance.

Using our innovative HEK293T LVVs suspension production system (PTLV-SMART) Figure 1, we are able to achieve a minimum of 70% CAR positive cells in drug products Figure 2.

Our Services

Thanks to our extensive experience and expertise, we are able to offer a complete, end-to-end service for cell therapy development and manufacture:

  • Discovery research and proof of concept
  • Process development, optimization, scale-up and scale-out
  • Analytical development, testing method verification and validation
  • Testing services for drug substance (DS) and drug product (DP)
  • cGMP manufacturing in either a fully closed automatic system or integrated units in a class
    B cleanroom environment
  • Regulatory submission
  • Plasmid, lentiviral vector and cell therapy process development, and GMP
    manufacturing

Viral Vectors - AAV

Teams dedicated to AAV development and cGMP manufacturing

We have around 40,000ft2 of laboratory space and R&D and process science teams dedicated to AAV development and manufacturing, including upstream process (USP) and downstream process (DSP) development, analytical development and DS/DP GMP manufacturing.

We provide discovery research, end-to-end AAV gene therapeutic product development, including plasmid manufacturing throughout AAV USP and DSP for DS, and ultimately DP fill and finish. We offer both mammalian cell HEK293 and insect cell SF9-based production systems, which provide flexibility to suit every client’s unique needs.

Our Services

Based on our capabilities and capacity, we are able to offer a broad portfolio of AAV services:

  • Mammalian HEK293 and insect SF9 AAV production systems
  • Adherent and suspension culture systems
  • Over 10 GMP manufacturing suites with up to 2,000 L bioreactor
  • Robust, DOE-based upstream and downstream processes
  • Scale-down modeling and scale-up processing
  • QbD experience supporting process characterization, control space and validation
    (PPQ), and clinical phase III product
    manufacturing and NDA submission
  • Robust analytical methods to ensure quality DS and DP production
  • Regulatory submission

Upstream Processes

We support design of experiments (DOE) to help clients optimize manufacturing process parameters such as MOI ratio, media, cell density, pH, CO2 etc. to develop a robust and productive AAV upstream process. Our teams have great experience working with different AAV serotypes.

Our AAV manufacturing suites are equipped to offer up to 2000L capacity. Our expertise and collective experience, dedicated PD and AD teams, and state-of-the-art facility and equipment make us a globally leading AAV CDMO.

Downstream Processes

Our robust DSP for AAV purification, includes cell lysis, clarification, TFF, exogenous virus clearance, affinity capture, IEX polish, ascetic filtration, and fill and finish at varied production scales. Our DSP teams have extensive experience in chromatography, enabling high quality DS and DP production. Figure 3 shows two examples in which AAV5 and AAV9 were produced with a high full to empty ratio (>97%) and high titer (1.11E+13 vg/ml).

viral vectors - lentiviral vectors

Proprietary LVV production system offering improved performance.

A lentivirus is a single-stranded RNA retrovirus that is widely used as a gene transfer tool in cell and gene therapies based on their ability to infect both dividing cells and differentiated non-dividing cells.

raditionally, lentiviral vectors (LVVs) are manufactured using an adherent cell production system with serum, but serum-free suspension cell systems have also been developed as an alternative. At Porton Advanced, we have developed a proprietary suspension HEK293T LVVs production system (PTLV-SMART) Figure 4 , which through cell line clonal screening, suspension adaptation, as well as assessment of viral packaging. Our innovative system has been successfully used in over a dozen of our clients’ projects at our facility.

We also offer other commercial LVV suspension production systems, according to our clients’ requests and needs, and we have successfully supported several of our clients in filing Investigational New Drug Applications (INDs).

Our Services

We offer the following LVV services, which uniquely position us to support our cell therapy clients:

  • Proprietary suspension HEK293T system with chemically defined medium (PTLV-SMART)
  • Commercial suspension HEK293F system with chemically defined medium
  • Adherent HEK293T systems with either reduced serum or serum-free medium (cells
    cloned and screened)
  • Dedicated process development and analytical development teams
  • State-of-the-art GMP facility with scalability up to 200L in suspension system and
    additional options for adherent cultures
  • Consistent productivity and quality

By integrating our LVV platform, we are able to provide an end-to-end service to cell therapy clients, spanning from DNA plasmid discovery research and GMP manufacturing, to LVV manufacturing process development and GMP manufacturing, and finally to cell therapy DS and DP production.

mRNA

High quality mRNA at high yields

mRNA is a promising and rapidly growing new class of advanced medicine, based on the speed of manufacture, ability to encode varied proteins, excellent safety and efficacy profile, and flexibility in modality and formulation.

At Porton Advanced, we have established mRNA manufacturing expertise, including in USP mRNA production (IVT, enzymatic/co-transcriptional capping poly(A) tailing, etc.), DSP mRNA purification (affinity chromatography, ion-exchange polishing, TFF, etc.) and lipid nanoparticle (LNP) delivery formulation Figure 5 and Figure 6. From transcriptional efficiency to stabilization of the mRNA products, we have demonstrated our ability to deliver high mRNA production yields while minimizing degradation.

Our Services

We are a trusted partner to our clients, providing end-to-end services that reach from plasmid process development through to GMP mRNA manufacturing:

  • Discovery research for 5’-capping, poly(A) tailing length and nucleotide modifications
  • mRNA process development, analytical development and LNP formulations
  • Co-transcription capping and tailing with maximum yield of 5mg/ml
  • mRNA DNA template manufacturing
  • GMP manufacturing for mRNA DS and DP

Example mRNA transcription

After co-transcription capping and tailing, mRNA yield can reach 5mg/ml.

LNP packaged mRNA

Lanes 3 and 6 show LNP packaged mRNA, which is too large to move into the agarose gel. Lanes 4 and 7 show mRNA bands after lipid coating dissolved using Triton X-100.

Oncolytic Viruses

OV process development and manufacturing tailored to your needs

Oncolytic viruses (OVs) are another promising therapeutic modality, which show great potential in treating many different types of cancers. Due to the large number of different oncolytic viruses, development and manufacturing must be specific and tailored to the individual needs of our clients. This demands a high level of understanding of the virus sciences and manufacturing technologies.

At Porton Advanced, we produce oncolytic viruses starting from the viral infection of VERO, A549 or HEK293 cells. Our teams specialize in cell line banking, viral seed stocking, and large-scale viral production. For example, we have a great deal of experience working with the adherent culture system that most OV production relies on.

Our Services

Porton Advanced provides a full range of CDMO services for oncolytic virus, providing flexibility in cell lines, virus seeds, adherent and suspension systems, cleanroom B and aseptic processes, etc.:

  • DNA genomic research, viral risk study, gene cloning and screening, etc.
  • Cell banking and viral seed stocking developments and GMP manufacturing
  • OV USP, DSP and analytical developments
  • Process and analytical method tech transfer, optimization, characterization, verification and Validation
  • IND and NDA CMC regulatory submission

We also have a dozen Class B cleanrooms, which allow us to perform aseptic manufacturing on a daily basis.

Plasmids

High quality plasmids at reduced cost

As a carrier of target genes, plasmids have significant impact on the quality, safety and effectiveness of the gene and cell therapy final products.

Our teams have years of proven experience in plasmid manufacturing, including construct optimization, colony selection, and GMP manufacturing process and analytical development. We understand the importance of lowering the production cost without compromising the quality, safety and effectiveness of the final CGT products.

Our Services

Our expertise in plasmid development and manufacturing includes:

  • High density fermentation platform technology
  • In-line continuous process of E.coli lysis
  • BIA two-step purification platform process
  • Chromatography purification process
  • Platform process for linearized plasmid production
  • Robust in-process and DS/DP testing methods

The manufacturing process

The plasmid manufacturing process primarily includes fermentation, lysis, and purification. Figure 7 shows the standard production process at our facility.

In the upstream process it is necessary to maximize the productive yield, while in the downstream process it becomes critical to remove any impurities, including host cell DNA (HCD), host cell protein (HCP), and safety contaminants such as endotoxin, bacteria and exogenous virus Figure 8.

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