LAUSR

The development and large scale production of human plasma-derived medicinal products has been amongst the earliest successes of industrial scale biotechnology, and has enabled significant progress in the treatment of several at the time unmet medical challenges: human serum albumin was a much needed treatment for critical care of trauma and burn victims during World War II, cryo-precipitate and the more purified factor VIII, factor IX and anti-inhibitor concentrates allowed for the treatment of hemophilia, and immune globulins provided for a treatment of immune deficiencies, and later autoimmune disorders. These early successes did, however, also reveal biological safety challenges, in that the collection of plasma from many thousands of donors as needed for large scale production resulted in the potential for exposure of plasma product recipients to the microbial risk of the donors contributing to the plasma collection process, which resulted in a dramatic number of virus transmissions. To mitigate these fatal consequences, an array of interventions was rapidly developed and implemented, and finally codified in regulatory requirements. The combination of measures in the area of donor selection, donation testing, and virus inactivation and removal, together called reduction processes, now firmly established as the safety tripod, have effectively addressed these earlier safety concerns, and today plasma products feature significant safety margins. The concept has proven so successful that it is now equally applied to and codified for cell-based biotechnology manufacturing platforms, and as we witness the rapid progress of advanced therapy medicinal products (ATMPs), it will be important to ensure that the learnings from more traditional biotechnology will help to avoid any unwelcome reminder of the universal presence of microbiological agents.