octapharma
For the treatment of VWD

Double Virus Inactivation

wilate® is a double virus inactivated VWF/FVIII complex:

 

Solvent/detergent process (TNBP/Octoxynol-9)

Solvent/detergent (S/D) process sets benchmarks in every aspect of effective virus elimination/inactivation. Although a number of viral inactivation steps have been shown to greatly enhance the safety of hemophilia products, S/D process is an established and proven methodology for highly infectious enveloped viruses.3

  • Octapharma was the first manufacturer to apply the S/D process to a large-scale production of FVIII concentrate
  • The S/D process destroys the lipid membrane of the viruses
  • Lipid-coated viruses, such as HIV, HBV, HCV, and WNV, are destroyed rapidly, effectively, and irreversibly
  • Since the introduction of the S/D process, no infections with HIV, HBV, HCV, and WNV or other lipid-coated viruses have been associated with S/D treated products
  • The viruses used in virus validation studies were selected to represent a broad spectrum of different physical-chemical properties and differing resistance to inactivation processes


Since the introduction of the S/D process, no infections with HIV, HBV, HCV, and WNV or other lipid-coated viruses have been associated with S/D treated products

S/D inactivation kinetics of Sindbis virus4,5 

page12chart1

S/D inactivation kinetics of HIV4,5

page12chart2

 

PermaHeat

PermaHeat is an optimized heat inactivation process that was developed to supplement the solvent/detergent (S/D) process. PermaHeat treatment (100°C, 2 h) inactivates a broad spectrum of both lipid-coated and non-lipid-coated viruses. All tested viruses are inactivated by at least 4 logs. This also applies to porcine parvovirus, which is known to be very heat resistant, more so than the human parvovirus B19.2


PermaHeat inactivation kinetics of HAV and Sindbis virus4,5

page13chart1

 

Total viral removal capacity

The total efficacy of the double viral inactivation process (without taking into account other process steps) is over 10 logs for lipid-coated viruses and more than 6 logs for non-lipid-coated viruses.1,2

Virus reduction during the wilate® manufacturing process1

Production step Virus reduction factor [log10]
Enveloped viruses Non-enveloped viruses
HIV-1 SBV BVDV PRV REO 3 HAV PPV
S/D treatment >7.5 >8.6 >4.2 >8.5 na na na
Ion-exchange
chromatography
nd nd nd nd 1.9 - 2.3 1.2 - 1.9 3.3
TDH treatment 4.9 - >5.8 >5.5 nd 4.0 - 4.9 >6.4 >5.7 2.6 - 4.1
Global reduction
factor
>12.4 - >13.3 >14.1 >4.2 >12.5 - >13.4 >8.3 - >8.7 >6.9 - >7.6 5.9 - 7.4

 

 

 

 

 

 

 

 

 

na = not applicable;
nd = not done (S/D reagents present);
HIV-1 = Human Immunodeficiency Virus – 1;
SBV = Sindbis Virus;
BVDV = Bovine Viral Diarrhea Virus;
PRV = Pseudorabies Virus;
REO 3 = Reovirus Type 3;
HAV = Hepatitis A Virus;
PPV = Porcine Parvovirus

 

Indications and Usage

wilate® is a von Willebrand Factor/Coagulation Factor VIII Complex (Human) indicated in children and adults with von Willebrand disease for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding. wilate® is not indicated for the treatment of hemophilia A.

Important Safety Information

wilate® is contraindicated for patients who have known anaphylactic or severe systemic reaction to plasma-derived products, any ingredient in the formulation, or components of the container.

Hypersensitivity or allergic reactions have been observed upon use of wilate® and may in some cases progress to severe anaphylaxis (including shock) with or without fever.

When using a factor VIII (FVIII)-containing von Willebrand Factor (VWF) product, the treating physician should be aware that continued treatment may cause excessive rise in FVIII activity. Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate® to avoid sustained excessive VWF and FVIII activity levels, which may increase the risk of thrombotic events.

Patients with VWD, especially type 3 patients, may potentially develop neutralizing antibodies (inhibitors) to VWF, manifesting as an inadequate clinical response. Since inhibitor antibodies may occur concomitantly with anaphylactic reactions, patients experiencing an anaphylactic reaction should also be evaluated for the presence of inhibitors.

wilate® is made from human plasma. As with all plasma-derived products, the risk of transmission of infectious agents, eg, viruses and, theoretically, the variant Creutzfeldt-Jakob disease (vCJD) agent or other unknown infectious agents, cannot be completely eliminated. Despite measures to reduce this risk, such products may still potentially transmit disease.

The most common adverse reactions to treatment with wilate® in patients with VWD have been urticaria and dizziness. The most serious adverse reactions to treatment with wilate® in patients with VWD have been hypersensitivity reactions.

Please see full prescribing information.

To report suspected adverse reactions, contact:
Octapharma USA Inc.
866-766-4860 or
FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch

References

1. wilate®, von Willebrand Factor/Coagulation Factor VIII Complex (Human) full prescribing information. 2009.

2. Data on file, Octapharma USA, Inc. 2009.

3. Farrugia A. Guide for the assessment of clotting factor concentrates for the treatment of hemophilia. World Federation of Hemophilia. Available at: http://www.wfh.org/2/docs/Publications/Safety_and_Supply/ GuideClottingFactor_Eng.pdf. Accessed January 29, 2010.

4. Stadler M, Gruber G, Kannicht C, et al. Characterisation of a novel high-purity, double virus inactivated von Willebrand factor and factor VIII concentrate (Wilate®). Biologicals. 2006;34:1-8.

5. Biesert L, Suhartono H, Klengel R, et al. Viral safety of a novel von Willebrand factor and factor VIII concentrate (wilate®): virus inactivation capacities of optimised solvent/detergent and terminal dry-heat treatments. Haemostaseologie. 2005. P110.

Photos are of models and for illustrative purposes only.

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