Today, cell engineering is one of the most successful applications of advanced medicine. Porton Advanced offers both autologous and allogeneic cell engineering platforms with integrated supports including CRO service, process development, analytical development, cGMP manufacturing, testing services, and regulatory assistance.
T cells are collected from the individual patient. This includes CAR-T, TCR-T, TIL, etc.
Cells are obtained from healthy donor pools, such as UCAR-T, NK/CAR-NK, γδ T, red cells, MSC, IPSCs, etc.
Thanks to our extensive experience and expertise, we are able to offer a complete, end-to-end service for cell engineering development and manufacturing:
Porton Advanced has developed a mature process platform and has accumulated rich CMC experience for different types of cell engineering. At the same time, we continue to invest resources in optimization and development of new process technologies to meet the needs and challenges of industry development.
For CAR-T or TCR-T, lentiviral static transduction is usually used without the addition of transduction enhancers. The VCN (Vector Copy Number) of healthy CD3-positive cells is controlled to be no more than 3, and CAR or TCR positive rate is 60~90%.
According to various client request, Porton Advanced designs and explores optimal electroporation proecess for efficiently knock-in/out target genes by numerous electroporation equipment (including Lonza, Thermo, Etta and so on).
To reach specification of cell engineering excipients, Porton Advanced can perform irradiation on feeder cells by our own irradiation equipment.
Porton Advanced has successfully obtained clinical approval for 18 IND applications since the launch of our first cell engineering cGMP production line back in 2020. We now provide CDMO services for dozens of cell engineering projects at varying stages such as investigator-initiated trials, preclinical trials, IND applications, clinical trials, and more. So far, Porton Advanced has 12 independent production lines, which allows us to simultaneously produce autologous cell products, allogeneic cell engineering products, and cell engineering products with more closed operations.
equipped with high-volume separation, cultivation, concentration, and filling equipment. Each line has one class B+A clean room and multiple class C operating rooms.
equipped with automated separation, cultivation, and concentration equipment. Each line has one class B+A clean room and several class C operations rooms.
multiple class C operating rooms with Class A isolators.
each line has one Class B operating room and multiple class C operating rooms.
automatic filling room with multiple B+A liquid dispensing rooms and multiple C+ isolators. Equipped with an IPC intermediate product control room, feeder cell irradiation room, sterilization room, inactivation room, material temporary storage room, Kitting sorting room, etc.
Porton Advanced provides three-tiered cell banking services (cell lines including MSC, k562, etc.) based on adhesion and suspension processes. Our technical team will establish a three-tiered cell bank in a cGMP environment and perform programmed cooling and cryopreservation to maximize cell viability.
Raw materials and excipients used in cell therapy generally should not contain any animal-derived components. Under Good Manufacturing Practices (GMP) conditions, we prefer to use materials classified as Cell Therapy Systems (CTS). If it is unavoidable to use raw materials that contain animal-derived components, it is essential to include residual testing both during the production process and as part of the final release testing.
Manufacturing changes may occur due to a variety of reasons, including improving product quality, expanding product supply, or improving manufacturing efficiency. Possible scenarios include transitioning from serum-containing to serum-free culture media and moving from manual to fully closed and automated systems. The main objective is to ensure product quality, safety, and consistency. It is highly recommended to adopt the principles of Quality by Design (QbD) and to integrate change management throughout the entire lifecycle to balance innovation with compliance.
Stem cell passage generally requires an additional five generations after formulation. For instance, if formulation occurs in the fifth generation, stability studies should evaluate the characteristics of cells in the tenth generation, focusing particularly on karyotype, STR, and functional biomarkers.
Stem cell passage generally requires an additional five generations after formulation. For instance, if formulation occurs in the fifth generation, stability studies should evaluate the characteristics of cells in the tenth generation, focusing particularly on karyotype, STR, and functional biomarkers.
Recommended tests for PBMC to generate iPSC include sterility testing, mycoplasma detection, p53 analysis, full genome sequencing, and adventitious agent testing.
The reprogramming method primarily involves two types of transfer systems: integrative and non-integrative. Integrative transfer systems, which utilize retroviruses and transposons, offer high efficiency but come with a lower safety profile. In contrast, non-integrative transfer systems, such as plasmids, mRNA, Sendai viruses, and recombinant proteins, have lower residual effects and a higher safety profile. Consequently, non-integrative transfer systems, particularly episomal vectors, are commonly used to develop induced pluripotent stem cell (iPSC)- derived cell therapies.
It is crucial to ensure batch-to-batch consistency in autologous cell therapy. For allogeneic cell therapy, extra attention should be given to evaluating immunological rejection (such as HLA matching) and donor screening (including infectious diseases and genetic disorders).
The CDE/FDA is transparent about its requirements for cell products, but they expect applicants to provide sufficient scientific evidence based on the product characteristics and patient needs. Currently, pharmaceutical companies prefer using cryopreserved cells because they are easier to scale up for universal CAR-T therapies and mesenchymal stem cells (MSCs), among others. However, for certain specific indications and cell products that are sensitive to cryopreservation (such as point-of-care (POC) cell products and some tumor-infiltrating lymphocytes), using fresh cells is often a better option. Ultimately, we must demonstrate the rationale for our choices through CMC data and non-clinical/clinical studies.
The CDE/FDA does not favor the use of either blood plasma or serum replacements for cell therapy production. However, it is highly recommended to use chemically defined media to ensure standardized manufacturing processes. If blood plasma is to be used, it is essential to validate its necessity and provide rigorous quality control data.
The essential requirements for excipients and reagents used in cell therapy include safety, the ability to mitigate exogenous risks, and complete traceability. Pharmaceutical companies must establish suitable manufacturing processes that align with Chinese regulations, which entail additional testing requirements for imported materials. Additionally, they should provide evidence of comprehensive quality control for all materials used.
A Pre-IND (Investigational New Drug) meeting is crucial for consulting with regulatory agencies, such as the FDA and CDE. Pharmaceutical companies should submit their research protocols, non-clinical data, and preliminary data from Chemistry, Manufacturing, and Controls (CMC) studies. This information is necessary to gather essential details, including clinical endpoints and key safety assessments, that will be addressed during clinical trials.
