A Practical Approach to Raw Material Sourcing and

ManagementCell Culture World Congress, Munich Germany

Marlin FrechetteDirector, Quality Systems and Regulatory Affairs

Irvine Scientific

Outline

Introduction

Raw Material Program• Historical Events• Program Elements

- Operational Excellence- Quality Excellence- Service Excellence

• Conclusion

Irvine ScientificIntroduction

40-year Cell Culture History• Global Coverage

Markets Served• Biopharmaceutical• Medical Markets • Cell Therapy

Parent Company – JX Holding (Japan)• 25 years

Raw Material ProgramHistorical Events

YearBiological Product or

VaccineContaminant

1940s Yellow Fever VaccineAvian Leukosis VirusHepatitus B Virus (28,000 cases)

1950s Polio Vaccine SV-40 and Polio (Cutter)

1980s Human Growth Hormone Creutzfeldt-Jacob

1980s Blood Derived Products, 1990s HIV, HBV, HCV, HAV

1990s Monoclonal Antibodies LCMV, MVM, EHDV

2000s Animal Derived Raw Materials BPyV, Cache Valley

2000s Recombinant Proteins Vesivirus, REO-Type 2, MVM

2010 VaccinesPorcine Circovuirus(DNA Sequences Only)

Source: “Cell Line Testing, Raw Material Considerations, and Regulatory Guidance”, by Alan Moore, A General Presentation to Irvine Scientific, May 6, 2011, WuXi AppTec

Raw Material ProgramElements

Raw Material Program

Operational Excellence

Fundamental Principles

Quality Excellence

Service Excellence

Best Practices Continuous Improvement

Custom Requirements

1. Sourcing Strategy

• Influences Supply Chain Transparency

Operational ExcellenceIndustry Best Practices

SuppliersStanda

rdPart #

Custom

Part #Total

Percent(%)

Total 46 27 51 -

Manufacturer 24 11 28 55%

Distributors 22 16 23 45%

Direct Manufacturer

52% 40% - -

Baseline• > 50% raw material components from manufacturers

Directive• Further minimize use of distributors where possible

Table 1. Manufacturers versus Distributors

2. Dual Sourcing• Supply Continuity• Risk Mitigation

Operational ExcellenceIndustry Best Practices

Raw Material Part Number

Standard

Custom TotalPercent

(%)289 153 442

Dual Sourcing

Primary 289 153 442 100%

Secondary 200 105 305 69%

Single Source (%)

31% 31% 43% 31%Baseline• 69% dual sourced

Directive• Continue to qualify secondary sources (risk-

based)

Table 2. Primary versus Secondary Sources

3. Supply Chain• Material and Supplier Qualification - Split• Risk-based Management

Operational ExcellenceIndustry Best Practices

Quality ExcellenceContinuous Improvement

1. Relevant Incoming QC Testing• Every receipt is tested (sampling plan)• Type and use• Annual trend analysis of incoming receipts

2. Material and Vendor Qualification• Split and implement into Supply Chain

3. Transparency to Tertiary Level• Good communication with manufacturers and distributors• Successful ACF raw material program

4. Proactive analysis of new requirements• Case Study

Quality ExcellenceCase Study

Observation: Multiple customer inquiries for non-detectable enteric bacterial organisms <per USP 62>.

Challenge: Requirement not currently implemented in supply chain.

Current Study: Establish baseline data and assess feasibility of non-detectable specification for enteric bacterial organisms 1. Raw Material Supply Chain

- Initiated discussions with vendors- Analysis of current inventory

2. Environmental Analysis (12-month)- Facilities, equipment, processess and practices

Study Strategy1. Raw Material Assessment

- Production Method- Supplier- Number of Lots

2. Baseline Data - Where to look- Rationale for next

steps

3. Directive- Begin routine

monitoring• Raw materials and

EM

Table 3: Raw Material Inventory by Production Method

Table 4: Raw Material Inventory Bioburden – Lots Received

Quality ExcellenceCase Study

Production Method

Lots

Lots w/ Bioburd

en Counts

Lots w/ Enteric

+

Lots w/ Bioburden

Counts (%)

Fermentation 101 23 0 22.8 %

Extraction 15 1 0 6.7%

Synthetic 73 9 0 12.3%

Steering Committee

Quality Group

1. Material & Vendor Qualification

• Sourcing Strategy• Dual Sourcing• Risk-based

Management

2. Change Notification

Operational Group

1. Supply Chain Implementation

• Sourcing Strategy• Dual Sourcing• Risk-based

Management

2. Change Notification

Must TalkMust

Respond

Challenge

Raw Material ProgramFunctionality

Execution

Raw Material ProgramSteering Committee

Raw Material Program

Operational Excellence

Quality Excellence

Service Excellence

Best Practices1. Supply Chain

Implementation2. Change Notification3. Relevant Testing

Continuous Improvement

1. Qualification Requirements

2. Change Notification3. Incoming QC Testing

Seamless Integration1. Customer Requirements2. Market Trends

Manufacturing Operations

Technical SupportSupply Chain

Quality AssuranceQuality Control

Technical SupportSales and Marketing

Steering Committee & Directives

Service ExcellenceSeamless Integration – Custom Needs

1. Custom Documentation Requirements• Raw material documentation

2. Inventory Management• Sequestered Inventory - Critical Raw Materials• Master Raw Material Lists / Requirements

3. Transparency to Tertiary Level• Troubleshooting• Change Notification

1. Ensuring Alignment with Industry Expectations• Proactive versus reactive

2. Practical Approach to Our Business• Risk-based management

3. Ensuring Execution• Business Continuity

Raw Material ProgramConclusion

Jim Niemeyer Alma Krebs Holden Harris Ashley Werner Tom Fletcher Erik Vaessen Deb Stutz

Acknowledgement

Director of Operations

Manager, Supply Chain

Manager, Quality Assurance

Manager, Quality Control

Director, Research & Development

EU Territory Business Manager

Director, Marketing