There are several new treatment products for bleeding disorders available today and over the next couple of years, even more will likely become available to the community.
Not only are “longer acting” factor VIII and IX products becoming available, but recombinant von Willebrand Factor (VWF) products, new treatments for the extremely rare disorders, and some products that may work to prevent bleeding but are not classified as clotting factor concentrates (CFCs) are all in development.
When there are more products to choose from and more countries choosing to purchase treatment products for bleeding disorders, World Federation of Hemophilia (WFH) national member organizations often turn to the WFH for guidance about product selection, in particular concerning the safety of these products.
There are also important questions about the supply of treatment products. When recombinant CFCs first became available, there were questions about what would happen to plasma-derived CFCs. Would they disappear or continue to be manufactured? The answer is now clear; plasma-derived products continue to be made and the quantities available each year continue to grow, albeit slowly. As every international unit of CFC produced is consumed, there is considerable room for growth in the global supply. It is likely that the new products coming out now will not replace the older recombinant products but will instead increase the total global supply of CFCs.
The WFH Treatment Product Safety, Supply and Access Committee oversees all WFH activities related to safety and supply issues. The committee includes patients, clinicians, and regulators. The aim is to monitor and comment on safety issues such as threats to plasma-derived products like variant Creutzfeldt-Jakob disease, and the pandemic viruses (Middle East Respiratory Syndrome, Hepatitis E, Zika virus) that could be blood borne.
Today, one of the biggest safety concerns that apply to all treatment products is inhibitors. Although developing inhibitors is a risk associated with all CFCs, it is not yet clear if there is an association between certain products or classes of products and elevated risk. As inhibitors are a rare complication of a rare disease, it is extremely hard without international collaboration to evaluate the risks involved. The WFH will continue to support initiatives that monitor these challenges and will inform our community of any progress.
The WFH cannot make determinations about specific products because the selection of safe, effective treatment products is the responsibility of national regulatory and health agencies. In the case of CFCs, whether plasma-derived or recombinant, safety and efficacy can only be assured by regulatory oversight of the entire production process.
Why not just test the final product to make sure it is safe? In fact, end-product testing cannot be used to assure viral safety of any type of CFCs. The tests used for screening plasma for viral agents, whether performed on donations or pools, and whether serologic or molecular, are not designed or validated for testing final products. Using these tests for final products is highly inappropriate and adds nothing to the assurance of safety to the products. End product testing may lead to incorrect assessments of product quality and safety and hold up product release. The regulatory agencies that oversee much of the production of recombinant CFCs (the US Food and Drug Administration, FDA, and the European Medicines Agency, EMA) do not test final products for viral safety.
As part of the WFH’s continuing efforts to provide guidance on product safety and supply, an updated Guide to National Tenders for the Purchase of Clotting Factor Concentrates was published in 2015. Later this year, the WFH will move our Registry of Clotting Factor Concentrates online. This valuable tool for assessing treatment products will be easier to use and will be updated with the most up-to-date information on more than a hundred treatment products. The WFH will also release a newly revised version of our Guide for the Assessment of Clotting Factor Concentrates which will include more discussion of recombinant CFCs, including the “longer acting” products that are now available.