Recombinant Generations

The term generation is a descriptor used to describe recombinant clotting factor products and the technology used to create them.

The qualifications to be labeled as one of the various generations vary with the factor type (VII, VIII or IX).

Over time new procedures were developed for the manufacturing of recombinant factors and as the newer processes became used, the term generation was born. Factor VIII products can be broken down into three generations. To simplify the manufacturing process; recombinant factors are no longer extracted factor proteins from human blood (which is how monoclonal and earlier factor products were made). Recombinant factor proteins are produced by cloned cells that were genetically engineered specifically for that purpose. These cells are grown in large vats where they release the factor protein as a byproduct. From here the protein is separated off, filtered and cleaned in its purification steps before moving on to being stabilized during the formulation process. After being stabilized the factor is ready to be shipped to people with bleeding disorders.

	First Generation	Second Generation	Third Generation
Culture Process
Purification Process
Stabilization Process
Denotes no blood product is used during this step: Denotes blood product usage during process:

• First Generation Recombinant Factors - are manufactured using a cloned cell bank to actually create the factor protein rather than simply extracting it from human plasma. While this generation no longer derives the factor from plasma ), it does use human blood products as food for cells during the culture process, as well as the purification and stabilization processes.
• Second Generation Recombinant Factors - While similar in production to the first generation recombinant product, second generation recombinants, stopped using human blood products to stabilize the final molecule but still use them during the culture process or both the culture and purification processes.
• Third Generation Recombinant Factors - have removed human blood from the production process all together.

There are only 1st Generation factor VII and IX recombinant products available, however the technology used in their production is equivalent to 3rd generation factor VIII products. They are termed 1st generation only because the process involved in their production has not been changed since they first became available and in no way implies the technology used in the factor VII and IX recombinants is older or less advanced than that used in 3rd generation recombinant factor VIII.