# Presentation: 432840

## Bovine Derived Products are Safe 

- TSE Advisory Committee
- Serologicals Corporation
- 12- 13 February 2004

## Meeting Objectives

- Provide information to the TSE Advisory Committee
- The Current Regulatory Environment
- Scientific environment
- What advances for testing animal products are available now
- Studies we should consider performing
- Lessons learned from previous experiences with BSE/TSE
- Regulatory Strategy for the Entire Industry
- Stay in the market!

## Serologicals

- Supplier of Animal Blood Protein Products
- Responsible Supplier
- Safety
- Quality
- Regulatory
- Serologicals' Manufacturing Operations division is now comprised of 2 main businesses:
- _[Serologicals Limited](http://seronet/web/mfg/limited/)__ _
- _[Serologicals Proteins](http://seronet/web/mfg/proteins/)_

## Types of Products

- ~90 distinct animal protein products (such as BSA)
- Supplied to life science companies
- Used in blood typing and other diagnostic reagents.
- Enhances detection of blood group antibodies
- Essential to the safe transfusion of blood
- Tissue culture media components
- Highly purified animal proteins
- Nutrient additives in cell culture media
- Bovine EX-CYTE® produced through patented manufacturing process
- Transferrin

## Application of Bovine Derived Cell Culture Products

- Products in our industry are Intended for Use in Further Manufacturing.
- Our Customers Use Our Products in the Manufacture of:
- Components in Clinical Diagnostic Kits
- Cell Culture Media Components used in  Manufacturing Processes for the Production of Medicines and Vaccines
- Reagents for Life Science Research

## What Happens Now When BSE is found in US Source Animals?

- Raw Material from Australia and/or New Zealand
- Alternative Materials
- Recombinant Proteins
- We are required to re-demonstrate Safety of Manufacturing Processes

## Alternatives to Animal Derived Materials?

- Recombinant proteins
- Not readily available
- Long development time
- Additional clinical trials
- Expensive for Pharma and Bio customers to convert
- We are negatively impacting worldwide economies by turning away from products *proven* to work in multiple product lines and applications

## BSE Action Strategy – Drivers

**USDA**

***“******BIO”***

***FDA***

***Congress, Senate***

***Big Pharma, Biotech, Diagnostic***

***NCBA***

- Industry

## Serologicals’ Approach to Minimizing Risk of BSE

- We use only US Sourced Material that is certified to comply with all regulations
- We are now limiting the acceptance of plasma to only animals less than 30 months old
- First shipment back into Canada was 06 Feb 2004
- We adhere to rigorous internal policies to control the use, location and disposal of materials.
- Our manufacturing processes include steps that have been demonstrated to reduce prion/viral loads

## BSE infectious agents - no practical detection method or RMs/Finished Products
Addresses theoretical risk of BSE & viral contamination
Possibility of unknown viral contaminants not detected by current protocols 
Satisfies biopharmaceutical customers
Assists with regulatory requirements - exportation into Europe
We need to deal with public perceptions

- Addresses theoretical risk of BSE & viral contamination
- Possibility of unknown viral contaminants not detected by current protocols
- Satisfies biopharmaceutical customers
- Assists with regulatory requirements - exportation into Europe
- We need to deal with public perceptions

- BSE & Virus Clearance Studies - *Why?*

## Why Do We Need to Require Studies for Removal of Adventious Agents?

- Not just for BSE/Viral concerns:
- Compete for nutrients in cell culture
- Disrupt cellular processes, cell division - log growth phase
- Infect cells, possible cytopathic effects
- byproducts reduce cell productivity, digest secreted proteins
- prions are not well understood
- Unknown agents - not yet identified
- biopharmaceuticals: agents ending up in human population?

## BSE Clearance Study: HS BSA & Aprotinin 

- Emulate production using lab scale process - BHL3
- Production - key points identified believed to impact infectivity: heating, filtration & ion-exchange
- Known titers of infectivity spiked at key process steps - downstream measurement
- Inoculate hamsters with 10-fold serial dilutions
- Compare  infectivity recovered vs. spike

- BSE Clearance Study: *HS BSA & Aprotinin**** ***

## BSE Clearance Study

- Detection of Infectivity:
- Clinical signs - examine hamsters for scrapie ~ 1 year
- Examine brain by Western Blot for presence of PrP
- Proteinase K - transformed PrP (amyloid) is resistant

## BSA: Viral Clearance

- Production - key points identified believed to impact viral infectivity: pH, heat,solvent fractionation
- Emulate production using lab scale process - dedicated virus facility
- Introduce challenge viruses prior to key process steps - select wide range of viruses
- Check infectivity downstream to process steps

## HS BSA: BSE Clearance

- Results:
- 2  heating & filtration steps plus 2 ion-exchange & charcoal filtration steps achieve a 16 Log total reduction in infectivity

- Conclusion:
- The manufacturing steps are very effective in eliminating a theoretical TSE contamination  - applies to part numbers 3301, 3305 & 3310

*Study Reprint is available online at www.Serologicals.com and Technical Support*

## Aprotinin: BSE Clearance

- Results:
- MeOH extraction, low pH, heating, AMS precipitation & ion-exchange chromatography: 17 Log total reduction in infectivity

- Conclusion:
- The manufacturing steps are very effective in eliminating a theoretical TSE contamination  - applies to part numbers 7105 & 7107

*Study Reprint is available online at www.Serologicals.com and Technical Support*

## BSA: Viral Clearance

- Challenge Viruses

## BSA: Viral Clearance

- Results: Cohn BSA

**Virus****	****Total Log Reduction in Virus Titer**
- IBR #1			7.33
- IBR #2			7.00
- BVD #1			6.00
- BVD #2			6.33
- BTV #1			6.00
- BTV #2			6.00
- PPV #1			3.5
- PPV #2			3.83

## BSA: Viral Clearance

- Results: HS BSA

**Virus****	****Total Log Reduction in Virus Titer**
- IBR #1			7.33
- IBR #2			7.33
- BVD #1			6.33
- BVD #2			6.00
- BTV #1			6.33
- BTV #2			6.00
- PPV #1			3.83
- PPV #2			3.83

## BSA: Viral Clearance

- Results:
- BVD, IBR & BTV:  6-7 Total Log reduction, regardless of the process
- PPV:  3.5-3.8 Total Log reduction, regardless of process
- Albumin yields for the fractionation process were within expected levels for the 2 processes

## Recommendations for BSE Risk Mitigation

- We should not require the medical device and pharmaceutical industry to move to animal free media solely due to BSE concerns:
- We should aggressively pursue requiring that animals are identified and tracked from birth herd to slaughter
- Require studies that demonstrate the removal of viruses and prions during the manufacturing processes
- Support/encourage the continued efforts of all agencies to have a consistent and immediately executionable plan for the NEXT occurrence of BSE in any country