How Factor VIII Products Differ
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Factor VIII products include both plasma-derived and recombinant formulations used primarily for treating hemophilia A and related bleeding disorders. Here is a comprehensive list of commonly available Factor VIII products:
Plasma-Derived Factor VIII Products
- Hemofil M®
- Koate-DVI®
- Monarc-M®
- Monoclate-P®
- Alphanate® (Factor VIII/VWF complex)
- Humate-P® (Factor VIII/VWF complex)
- Wilate® (Factor VIII/VWF complex)
Recombinant Factor VIII Products
First Generation:
- Recombinate®
Second Generation:
- rFVIII-FS (Helixate®, Kogenate®)
- Moroctocog alfa (ReFacto®)
Third Generation:
- Advate®
- Kovaltry®
- Moroctocog alfa (Xyntha®)
- Turoctocog alfa (Novoeight®)
Fourth Generation:
- Simoctocog alfa (Nuwiq®)
Extended Half-Life (EHL) Recombinant Factor VIII Products
- Octocog alfa pegol (Adynovate®) [PEGylated]
- rFVIII–Fc fusion protein (Eloctate®)
- rFVIII-SC (Afstyla®) [Single-chain recombinant FVIII]
These products vary by technology, source (plasma-derived vs recombinant), half-life, and generation (advancements in manufacturing and molecular modification).
Recombinant and plasma-derived Factor VIII differ primarily in their source, manufacturing process, safety profile, and immunogenicity risk.
Source and Manufacturing
- Plasma-Derived Factor VIII is extracted and purified from human donor plasma. It includes coagulation factor VIII combined with other plasma proteins such as von Willebrand factor (vWF). Viral inactivation steps are applied to reduce transmission risk of blood-borne pathogens.
- Recombinant Factor VIII is produced using genetically engineered cell lines (e.g., hamster ovary cells), without relying on human plasma. Recombinant products do not contain human plasma proteins like vWF unless specifically designed to do so.
Safety
- Plasma-derived products have inherent risks related to viral transmission despite rigorous viral inactivation (historically linked to HIV, hepatitis outbreaks).
- Recombinant factor VIII significantly reduces the risk of transmitting blood-borne viruses because it is synthesized in controlled cell culture systems.
Immunogenicity and Inhibitor Development
- There is evidence suggesting that recombinant Factor VIII carries a higher risk of inhibitor development (neutralizing antibodies against FVIII) compared to plasma-derived concentrates. Some studies report approximately 2 to 3 times greater risk with recombinant FVIII, especially in previously untreated patients.
- Plasma-derived FVIII products containing vWF may have a protective effect against inhibitor formation, but findings are mixed and not conclusively proven.
- Both types of products have been extensively studied, with no absolute consensus, although some clinical trials and meta-analyses indicate lower inhibitor incidence with plasma-derived FVIII.
Summary
| Feature | Plasma-Derived FVIII | Recombinant FVIII |
|---|---|---|
| Source | Human plasma donor | Genetically engineered cell lines |
| Viral transmission risk | Low but historically present | Very low (no human plasma involved) |
| von Willebrand factor (vWF) | Present in some products | Generally absent unless engineered |
| Immunogenicity | Possibly lower inhibitor risk | Higher inhibitor risk reported |
| Production availability | Limited by plasma availability | Unlimited production potential |
In practice, the choice between plasma-derived and recombinant Factor VIII depends on safety concerns, inhibitor risk, availability, and patient treatment response.
References
- PMC article on plasma-derived versus recombinant Factor VIII concentrates for hemophilia treatment (2003)
- PMC article on Factor VIII safety comparing plasma-derived and recombinant products (2010)
- Frontiers in Immunology article on immune responses to plasma-derived versus recombinant FVIII (2021)
- Cureus systematic review and meta-analysis on the impact of recombinant versus plasma-derived Factor VIII on inhibitor development (2022)
Humate-P Cheat Sheet
https://info.pharkeep.com/humate-p-cheat-sheet.html
Additional Readings
Understanding Humate-P Potency Values: A Clinical Guide for Pharmacists
The appropriate dispensing and administration of Humate-P requires a sophisticated understanding of its dual potency labeling system and the clinical indication for which it is prescribed. This comprehensive analysis addresses the critical challenges pharmacists face when prescribers provide doses in international units without specifying whether the dosing should be based
Kevin Van, PharmD, BCPS (Editor)
Humate-P Potency Units: Getting the Numbers Right in Clinical Practice
Humate-P’s labeling includes two potency values—one for VWF:RCo and one for Factor VIII (FVIII:C)—because it is a plasma-derived concentrate that contains both von Willebrand factor (VWF) and factor VIII.
Kevin Van, PharmD, BCPS (Editor)
How to reconstitute HUMATE-P using Mix2Vial
Before reconstitution, HUMATE-P can be safely stored at room temperature (up to 25°C [77°F]) for up to 36 months. (After reconstitution, HUMATE-P should be used within 3 hours.) How to take Humate-P | Humate-PHumate-P is available in a variety of vial sizes. This may help make accurate dosing easier,
Kevin Van, PharmD, BCPS (Editor)
What Does the “P” in Humate-P Stand For?
In Humate-P, the “P” means Pasteurized—a safety step where the product is heated to 60°C for 10 hours to inactivate viruses while preserving clotting factor activity, ensuring safe and effective treatment for VWD and hemophilia A.
Kevin Van, PharmD, BCPS (Editor)