Cell therapy final fill
Final fill is a critical step in cell therapy production. Not only does it represent the culmination of your product investment, but it’s also the final step before delivery to patients. We understand that cell therapy drug products are configured in different ways depending on the required delivery of the cells/tissues. Trust Avantor as your partner in this vital stage.
Assuring cell therapy integrity
Delivery of chondrocytes for cartilage repair is administered by an injection. Expanded cell doses are stored frozen and thawed for delivery via IV. Finally, skin grafts are stored in packaging to ensure the integrity of individual sheets of cells. In most cases excipients used to prepare the cell dose are decided by the customer. Assurance of cell culture components removal is critical, especially if cytokines and animal sera are used.
Ensuring the quality of cell therapy
The reduction of microbial (bacterial and fungal), endotoxin, mycoplasma, and virus contamination is extremely critical to ensure the quality of the drug substance and the quality and safety of the drug product. It is routine that the control of these contaminants is initiated through establishing relevant specifications of the raw materials used in bioprocessing applications. Confirmation that microbial bioburden is low, or below the level of detection for the assays, is essential.
Control is influenced by aseptic procedures followed in the production environment and is adhered to by employee training, gowning, cleaning, and environmental control. Process validation steps are followed to ensure an acceptable sterility assurance level for the drug substance and drug product being manufactured.
Since biologic production involves the use of living organisms (microbial and mammalian cells), the amount of debris (e.g., host cell protein, dead and living cells, and contaminating DNA) during the upstream phase of production is significant. And due to the concentration step following protein capture, there may exist levels of undetectable viruses resulting from raw materials, the cells used, or by production technicians. However, there are steps during the downstream phase of production designed to reduce or eliminate these concerns.
As aseptic production methods and approaches to validate these methods are not absolute, it is standard practice to perform various assays on drug substances and drug products to confirm product sterility, lack of contaminating mycoplasma, endotoxin levels, and confirmation that viral contaminants have been removed. It is also required to test for the absence of live and dead cells, host cell proteins, and contaminating DNA.
We offer an extensive line of assays appropriate for the uses described above. For microbial and mycoplasma, we have available “real-time” assays (results in minutes) and confirmatory “longer-time” (results in days/weeks) assay products. To measure endotoxin levels, we offer both chromogenic and gel clot quantification assays.
Lastly, to measure if host cell proteins have been removed, we offer ELIZA based test kits. For viral RNA, DNA, and other contaminating nucleic acids, we provide kits for extraction, amplification and detection, covering bead technology for extraction, and qPCR for amplification and detection.
Avantor manufacturers and distributes biopharmaceutical products and excipients providing structured choice and risk mitigation – for biopharmaceutical development, pilot scale and commercial manufacturing.
Maintaining environmental control during the manufacturing or down packing process is part of managing your risk. Avantor offers products from industry-leading manufacturers backed by a team of specialists with technical and industry experience to recommend the best solutions to meet your needs. Our controlled environment specialists are trained on ISO and IEST protocols. As members of IEST and PDE, they remain current on environmental control manufacturing industry trends and codes.
Confirmation that microbial bioburden is low, or below the level of detection for the assays, is essential. It is routine that the control of these contaminants is initiated through establishing relevant specifications of the raw materials used in bioprocessing applications.