WEST NILE VIRUS

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• WEST NILE VIRUS
• FDA Blood Product Advisory Committee Meeting
• 13 to 14 March 2003
• Dominique Pifat, Ph.D.
• Bayer Biological Products
• on behalf of
• PPTA Viral Safety Working Group

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Flaviviridae
Pestiviruses Bovine viral diarrhea
virus Classical swine fever virus Border disease
virus
Flaviviruses Tick-borne encephalitis viruses St.
Louis encephalitis Dengue viruses Yellow Fever
virus West Nile Virus
Hepaciviruses Hepatitis C Virus


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TRANSMISSION THROUGH BLOOD PRODUCTS

• FDA response October 3, 2002
• Information about West Nile Virus and Blood
  Safety
• FDA response October 25, 2002
• Guidance for Industry Recommendations for the
  Assessment of Donor Suitability and Blood and
  Blood Product Safety in Cases of Known or
  Suspected West Nile Virus Infection
• FDA has reviewed the viral reduction processes
  in place for all plasma derivatives. The methods
  in place have been validated to inactivate
  flaviviruses related to WNV.

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Different enveloped viruses are very susceptible
to a number of different inactivation methods
Similar Susceptibilities



Enveloped viruses with a broad range of physical
characteristics have been shown to be similarly
susceptible to inactivation methods
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FDA WORKSHOPNovember 4 5, 2002

• OUTCOMES
• The WNV data presented support the FDAs
  conclusion, in that WNV does not behave
  differently than other flaviviruses.
• The data presented at the November FDA workshop
  confirm that
• The concept of using a range of
  physicochemically diverse model viruses for the
  validation of virus reduction steps has also been
  verified, in that the behaviour of a virus of
  interest, i.e. WNV, has been adequately predicted
  !

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Progress since November 2002

• At the FDA workshop PPTA announced that member
  companies would commitment to perform
  verification studies with West Nile Virus
• Since then, PPTA member companies have generated
  additional supportive data on the inactivation of
  West Nile Virus in a variety of processes and
  using a number of inactivation and removal
  methods.

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Pasteurization
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Pasteurisation Inactivates Viruses (heat
treatment/stabilised aqueous solution/60C)
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Pasteurisation Inactivates Viruses (heat
treatment/stabilised aqueous solution/60C)
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Pasteurisation Inactivates Viruses (heat
treatment/stabilised aqueous solution/60C)
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Pasteurisation Inactivates Viruses (heat
treatment/stabilised aqueous solution/60C)
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Inactivation of WNV BVDV during 60C
Pasteurization of HPPS
WNV
BVDV
? 5.9 log10 reduction (setpoint) ? 6.2 log10
reduction (half conc.)
? 6.1 log10 reduction
? 7.3 log10 reduction
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Inactivation of WNV BVDV during 60C
Pasteurization of Prolastin
WNV
BVDV
? 4.9 log10 reduction
? 6.4 log10 reduction
?
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West Nile Virus, and relatives / model viruses
and WNV for verification
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Solvent Detergent
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Inactivation of WNV BVDV during TNBP/Tween
Treatment of Koate
WNV
BVDV
? 2.4 log10 reduction (setpoint) ? 5.2 log10
reduction (half conc.)
? 6.0 log10 reduction (setpoint) ? 6.1 log10
reduction (half conc.)
LOD (0.3 TNBP/1 Tw)
LOD (0.15 TNBP/0.5 Tween)
Except for the 0.5 hr samples, all WNV
infectivity was at the limit of detection.
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Inactivation of WNV BVDV during TNBP/Cholate
Treatment of IGIV
WNV
BVDV
? 5.9 log10 reduction (setpoint) ? 6.2 log10
reduction (half conc.)
? 4.0 log10 reduction (setpoint) ? 3.8 log10
reduction (half conc.)
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West Nile Virus, and relatives / model viruses
and WNV for verification
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Other Methods
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West Nile Virus, and relatives / model viruses
and WNV for verification
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West Nile Virus, and relatives / model viruses
West Nile Virus verification study
Asahi 15 N nanofiltration of ?1-Proteinase
Inhibitor Assay NGI, SuperQuant RT PCR Assay
for WNV
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West Nile Virus, and relatives model viruses and
WNV for verification
B Horowitz E Ben-Hur, Ann. Med. (2000) vol.
32, p. 475
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Conclusions (1)
BVDV A RELEVANT MODEL FOR WNV

• BVDV closely resembles flaviviruses including
  WNV
• BVDV has been successfully used to model HCV
  inactivation
• The largest body of inactivation data exists
  for BVDV
• These data provide assurance that WNV will be
  inactivated during plasma - derived product
  manufacture
• Studies performed with WNV demonstrate the very
  effective inactivation capacity of dedicated
  virus inactivation steps
• The data presented here confirm that studies
  utilizing a broad spectrum of model viruses are
  predictive of the behavior of other enveloped
  viruses such as WNV. Such studies will continue
  to be predictive in the future

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Conclusions (2)

• A successful precedent for a collaboration
  between
• Regulators
• Academia
• Patient organizations
• Industry
• ? to the ultimate benefit of concerned patients
  !!