# Presentation: 688176

## 
Risk assessment: The Safety of Blood Products
presented by
Dr. Thomas R. Kreil
Baxter BioScience
on behalf of the
PPTA Pathogen Safety Steering Committee

Technical meeting with FDA
April 29, 2003

**Risk assessment: The Safety of Blood Products**
***p******resented ******b******y***
**Dr. Thomas R****.**** Kreil**
**Baxter BioScience**
***o******n behalf of****** the***
**PPTA Pathogen Safety Steering Committee**
**Technical meeting with FDA**
**April 29, 2003**

- 29.04.03

##  Risk assessment considerations

** ****Risk assessment considerations**
** ****Plasma viremia **
** ****Infectious virus titer of positive units **
** ****Prevalence of viremia in the population **
** ****Resulting plasma manufacturing pool loads **
** ****Reduction by manufacturing processes **
** ****Further relevant features **

- 29.04.03

## West Nile Virus - Viremia

** ****10****2**** – 10****5**** iu/ml: in patients with underlying malignant disease**
**CM Southam & AE Moore, Am J Trop Med Hyg [1951] 31: 724**
** ****2.5 x 10****6**** c/ml: 3 days after onset of neurological symptoms**
**C Huang et al., **_[http://](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[www](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[.](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[cdc](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[.](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[gov](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[/](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[ncidod](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)__[/EID/vol8no12/02-0532.htm](http://www.cdc.gov/ncidod/EID/vol8no12/02-0532.htm)_
_**Otherwise Healthy Donors**_
** ****1-5 x 10****3**** c/ml: FDA BPAC briefing package, March 13, 2003**
** ****2 x 10****5**** c/ml: 1 in 7,107 (out of samples 75% targeted for risk )**
**A Conrad / NGI, BPAC March 13, 2003**
**	**_****__** **__**worst case: 2 x 10**__**5**__** PCR copies/ml**_

- 29.04.03

## West Nile Virus

** ****Mean PCR detectable amount of virus:****	****0.00289 pfu/mL (0.001640 – 0.005099 pfu/mL)**
-  A Conrad / NGI, BPAC March 13, 2003; CDC WNV panel (Lanciotti)
** ****Assuming that already ONE copy is PCR detectable:******** **_**1 infectious virus particle per 346 (196-610) genomes**_
** ****Viremia of max. 2x10****5**** PCR detectable genomes, ****	****at only 1 infectious particle per 196 genomes:**
****** **_**worst case: max. 1,020 infectious units per ml**_

- 29.04.03

## West Nile Virus

****** ****Modeling approach **
** ****US average risk: 0.36 per 10,000 donors**
** ****US maximum risk: 1.55 per 10,000 donors (peak epidemic)**
** ****Michigan: about 4 per 10,000 donors (during the epidemic)**
** ****Michigan: about 10 per 10,000 donors (peak epidemic, Sept 1)**
** ****Detroit: up to 20 per 10,000 donors (peak epidemic, Sept 1)**
- Dr. Lyle Petersen / CDC: BPAC, March 13, 2003 http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3940t1.htm

- 29.04.03

## West Nile Virus

** ****Samples from Cleveland and Detroit:****	****i.e. **_**highest risk areas**_** **
** ****Obtained during the first three weeks of September 2002: ****	****i.e. **_**highest risk period**_
** ****model: estimated risk ~ 8.2 per 10,000 in that population.**
** ****TaqMan PCR: 6 / 5,761 samples positive, ****	****i.e. viremia prevalence:**
_** **__**worst case: 10.4 per 10,000**_

- Dr. Sue Stramer / ARC: BPAC, March 13, 2003 http://www.fda.gov/ohrms/dockets/ac/03/transcripts/3940t1.htm

**P****revalence of viremia in the population**

- 29.04.03

## West Nile Virus

**Max. viremia levels: ****	****	****	****	****1,020 infectious units / ml**
**Dilution of viremic donations into manufacturing pools:******** **_**maximum of 1 infectious unit per ml**_**, assuming the**
** ****highest potential load, and the**
** ****highest prevalence**** **
_****__** **__**WORST CASE **_**(earthquake during a hurricane)**

**R****esulting plasma pool loads**

- 29.04.03

## West Nile Virus

** ****Infectious virus titer of positive units: ~10 units/ml****1 infectious virus particle per 346 genomes, i.e. mean of determined range**
** ****Prevalence of viremia in the population: 2/10,000****average risk throughout the U.S., during peak epidemic**
** ****Resulting plasma manufacturing pool loads: ****	****	**_****__** **__**~0.001 units/ml**_
** ****PLUS: reduction by manufacturing processes !**

**	****Base case**

- 29.04.03

## West Nile Virus

** ****WNV would be below the limit of detection for ****current virus assays **
**Inconsistent with current practice for ****HIV, HCV and HBV**

_**R**__**esulting plasma pool loads**_

- 29.04.03

## West Nile Virus

****** **_**complete inactivation of WNV**_
**	****reduction factors ranging between >5.5 and >8.2**
****** **_**very rapid inactivation kinetics of WNV**_
****** ****verification of the fact that WNV behaves exactly like ****	****predicted from model virus (BVDV, TBEV) data !!**

**R****eduction ****by**** manufacturing process****es**

- 29.04.03

## West Nile Virus

** ****only dedicated steps considered**
** ****For manufacturing process, the overall virus reduction capacity is determined by a combination of **_**virus inactivation and virus removal**_**.**
** ****only inactivation investigated**

**R****eduction ****by**** manufacturing**** process****es**** ?**

- 29.04.03

## West Nile Virus

**Acute self-limiting infection****:****	****life-long test-based donor deferral is only prudent                                                      for chronically-infected persons **** **
**	******** ****No medical benefit to the donor**
**	******** ****No public health benefit from WNV testing**

**Further relevant features**

- 29.04.03

## Conclusions:

Donation loads below limit of detection for current test strategies 
Typical flavivirus characteristics 
 Effective viral reduction by existing processes

**Donation loads below limit of detection for current test strategies**** **
**Typical flavivirus characteristics **
** ****Effective viral reduction by existing processes**

- West Nile Virus

- 29.04.03