Assays for final fill

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.