# Presentation: 490857

## 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

- 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

## Flaviviridae

**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

## 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.“**

## Similar Susceptibilities

**Enveloped viruses with a broad range of physical characteristics have been shown to be similarly susceptible to inactivation methods**

**Similar Susceptibilities**

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

##  FDA WORKSHOPNovember 4 & 5, 2002 

**OUTCOMES**
- „The WNV data presented support the FDA‘s 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 !“

## 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.

## Pasteurization

## Pasteurisation Inactivates Viruses (heat treatment/stabilised aqueous solution/60°C)

**Pasteurisation**** Inactivates Viruses ****(heat treatment/stabilised aqueous solution/60°C)**

## Pasteurisation Inactivates Viruses (heat treatment/stabilised aqueous solution/60°C)

**Pasteurisation**** Inactivates Viruses ****(heat treatment/stabilised aqueous solution/60°C)**

## Pasteurisation Inactivates Viruses (heat treatment/stabilised aqueous solution/60°C)

**Pasteurisation**** Inactivates Viruses ****(heat treatment/stabilised aqueous solution/60°C)**

## Pasteurisation Inactivates Viruses (heat treatment/stabilised aqueous solution/60°C)

**Pasteurisation**** Inactivates Viruses ****(heat treatment/stabilised aqueous solution/60°C)**

## WNV

**WNV**

**BVDV**

****** ****5.9 log****10**** reduction (setpoint)**
****** ****6.2 log****10**** reduction  (half conc.)**

****** ****6.1 log****10**** reduction**

**Inactivation of ****WNV**** & ****BVDV**** during **
**60°C ****Pasteurization**** of HPPS**

****** ****7.3 log****10**** reduction**

## WNV

**WNV**

**BVDV**

****** ****4.9 log****10**** reduction**

**Inactivation of ****WNV**** & ****BVDV**** during **
**60°C ****Pasteurization**** of Prolastin**

****** ****6.4 log****10**** reduction**

****

## West Nile Virus, and relatives / „model viruses and WNV for „verification“

## Solvent Detergent

## WNV

**WNV**

**BVDV**

****** ****6.0 log****10**** reduction (setpoint)**
****** ****6.1 log****10**** 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.

****** ****2.4 log****10**** reduction (setpoint)**
****** ****5.2 log****10**** reduction  (half conc.)**

**Inactivation of ****WNV**** & ****BVDV**** during ****TNBP/Tween**
** ****Treatment of Koate**

## WNV

**WNV**

**BVDV**

****** ****5.9 log****10**** reduction (setpoint)**
****** ****6.2 log****10**** reduction  (half conc.)**

****** ****4.0 log****10**** reduction (setpoint)**
****** ****3.8 log****10**** reduction  (half conc.)**

**Inactivation of ****WNV**** & ****BVDV**** during ****TNBP/Cholate**
** ****Treatment of IGIV**

## West Nile Virus, and relatives / „model viruses and WNV for „verification“

**West Nile Virus, and relatives / „model viruses and WNV for „verification“**

## Other Methods

## West Nile Virus, and relatives / „model viruses and WNV for „verification“

**West Nile Virus, and relatives / „model viruses and WNV for „verification“**

## West Nile Virus, and relatives / „model viruses“

**West Nile Virus „verification“ study**

- Asahi 15 N nanofiltration of 1-Proteinase Inhibitor
- Assay: NGI, SuperQuantTM RT PCR Assay for WNV

## West Nile Virus, and relatives: model viruses and WNV for „verification“

- * B Horowitz & E Ben-Hur, Ann. Med. (2000) vol. 32, p. 475

## Conclusions (1)

**  ****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**

**Conclusions (1)**

##  A successful precedent for a collaboration between

 Regulators
 Academia
 Patient organizations
 Industry
 to the ultimate benefit of concerned patients !!

-  Regulators
-  Academia
-  Patient organizations
-  Industry
****** **_**to the ultimate benefit of concerned patients !!**_

**Conclusions (2)**