A practical approach to raw material sourcing and management in cell culture


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A practical approach to raw material sourcing and management in cell culture

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  • Thank you all for being here today, I am very excited to be here, to present our raw material sourcing and management program. As Quality Director, I am very passionate about this subject and I know from experience that many in the cell culture industry share the same passion with me. We deeply believe that raw material and it’s management play a very critical role at the reducing risk during the manufacturing of biopharmaceuticals.
  • Many of you are familiar with Irvine Scientific and some might not be, so I will present a brief introduction of our company and an overview of our recently formalized raw material program, historical events, program elements, which includes quality, operational and Service and I will conclude with an explanation as to why we decided to formalized our raw material program.
  • IS is a cell culture media company. Established in 1970 originally as a serum supplierwithin a few years expanded the product offering to include cell culture productsToday, we are cell culture media supplier and that is what we do, it is the sole business of our organizationAs a media company we serve three markets the Biopharmaceutical for Industrial Cell Culture applications, the medical market with ART products, and the cell therapy with specialty media. Our parent company JX Holding with headquarters in Japan.
  • Many of us are familiar with the historical events that have taken place with contaminated products by an unexpected contaminants.We know that the evolution with the raw material requirements have been driven by industry impacting events. We recognized the importance to address risk whether actual or potentialWe have gain perspective and understanding basically not only what can go wrong, but learning what can we do to prevent it. Those responsible for Cell Culture manufacturing process are concerned with the risk of process contamination and we as media supply partner play a role at minimizing the risk.
  • I was talking about raw materials controls and concerns over 10 years ago… Issues associated with raw materials and the supply chain is a topic here to stay. Last year we decided to take a more integrated approach to managing current and potential challenges with raw material supply (both for us and our customers) by creating an internal program called ‘The Raw Material Program. While we have always had the operational and quality elements as they relate to raw material management, our program now takes a more integrated approach. I’ll now walk you through each of the three major components of our program which incorporates best practices, a continuous improvement approach, and integration of custom requirements.
  • Operational: I am going to talk about three top priority. The first priority we identified, was sourcing strategy, which impacts our ability to manage toward this transparency and is therefore our first priority within the program. The first thing we did was assess how the status of manufacturers vs. distributors with our raw materials We manage our raw materials in two categories – Irvine Scientific’s general inventory and inventory dedicated to specific customer requirements. This table provides an example of our approach, which was to have a clear understanding of what we had in terms of direct manufacturers and distributors. Knowing where we were starting, our internal directive is to further our use of direct manufacturers where possible.
  • The second operationalstrategy:Dual sourcing, ensures supply continuity and is a preventive measure to avoid production delays. It was very important to understand where we were at in terms of single and secondary sources, a analysis was completed to understand our base line.
  • The supply chain is the third critical priority in our program it was something in existing and for this part we are very strong, this operational functionality if is very robust5 key elements: Supplier qualification, material qualification, Change notification, purchasing controls and inventory controls. While they currently exists and operates in a robust manner, the objective of our program is to continue to focused in a risk based management.
  • Relevant Incoming QC: testing by type and how the raw material is used, it’s impact in the final product, Industry accepted sampling plan ANSI.Z1.4 Normal of ISO 2859Material and vendor qualification:Transparency to Tertiary LevelGood Communication with manufactures and distributors That is what allowed us to implement a succesfull ACF raw material program, part of the program is to certified all the components have to be certified by the suppliers free of animal component to the tertiary level of exposure. TL= Primary animal tissue, secondary animal enzyme in the mfg process, tertiary exposure, the enzyme is not animal derived, but there was exposure during the production of the enzyme As a custom media partner we have a very unique advantage, we received many request from our customers and with this have the opportunity to learn new requirements. In a moment I will present a case study that was generated from a custom request. At times some industry requirements are real and sometimes might not be feasible or value added, but this is our responsibility to know.
  • Inquiries enteric free media. An assessment had to be done, since this type of testing was not normally performed on all raw materials and final products. Our challenge was in the supply chain, as we investigated our suppliers informed us that they were not testing for this specific organism. Steps were taken to determine current conditions of raws, environment, associated equipment and practices. Once we found where we were at we can make decisions on how to move forward.
  • Raw materials were chosen based on their prevalence in ICC formulations. These were tested for standard bioburden in addition to enteric bioburden.Studies showed some materials (fermentation) were more susceptible to bioburden in general, Enteric was not seen in the raw materials at all.What we learned is that some were more susceptible and that we should continue to monitor these more. The message is that for this customer their formulations we were able to implement Enteric free specification.TSAT= Trypticase Soy AgarSAB= Sabouroud Dextrose AgarVR= Violet red Bile Glucose Agar
  • RM functionality:Quality created a directive for the operational group, in terms of material and vendor qualification. (Sourcing strategy, dual sourcing,….) operational group must execute and integrate the direction into the supply chain.While the functionality was always there, the challenge was that the priorities were not always in alignment, therefore the execution is not always in alignment. How did we solved the challenge? We included an additional piece to the functionality technical and sales and marketing and created an internal steering committee to improve execution.
  • The steering committee includes operations, quality, technical, sales and marketing groups. This committee is going to assess the needs of our business, will determine priorities and strategies and ensures alignment with industry requirements and a very critical piece a seamless integration of our customer requests.
  • Here are some examples seamless integration of our customer requirement for custom products.
  • At the end of our day, we want our business to be in alignment with industry expectations. Want to take a practical approach to our business utilizing risk based and value added strategies. Ultimately our goal is to ensure business continuity and no interruption of our supply from our suppliers to our customers.
  • I would like to Acknowledge the steering committee team for collaborating tirelessly to the success of our Raw material program
  • A practical approach to raw material sourcing and management in cell culture

    1. 1. A Practical Approach to Raw Material Sourcing and Management Cell Culture World Congress, Munich Germany Marlin Frechette Director, Quality Systems and Regulatory Affairs Irvine Scientific
    2. 2. Outline  Introduction  Raw Material Program • • Historical Events Program Elements - • Operational Excellence Quality Excellence Service Excellence Conclusion
    3. 3. Irvine Scientific Introduction  40-year Cell Culture History •  Markets Served • • •  Global Coverage Biopharmaceutical Medical Markets Cell Therapy Parent Company – JX Holding (Japan) • 25 years
    4. 4. Raw Material Program Historical Events Year Biological Product or Vaccine Contaminant 1940s Yellow Fever Vaccine Avian Leukosis Virus Hepatitus 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 Vaccines Porcine 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
    5. 5. Raw Material Program Elements Best Practices Continuous Improvement Custom Requirements
    6. 6. Operational Excellence Industry Best Practices 1. Sourcing Strategy • Influences Supply Chain Transparency Suppliers Total Standar Custom d Part # Part # Total Percent (%) 51 - 24 11 28 55% Distributors • 27 Manufacturer Baseline 46 22 16 23 45% Direct Manufacturer 52% 40% - - Table 1. Manufacturers versus Distributors > 50% raw material components from manufacturers Directive • Further minimize use of distributors where possible
    7. 7. Operational Excellence Industry Best Practices • Supply Continuity Risk Mitigation Baseline • 69% dual sourced Custom Total 289 153 442 289 153 442 100% Secondary • Standar d Primary Dual Sourcing 2. 200 105 305 69% Single Source (%) 31% 31% 43% 31% Raw Material Part Number Dual Sourcing Table 2. Primary versus Secondary Sources Directive • Percent (%) Continue to qualify secondary sources (riskbased)
    8. 8. Operational Excellence Industry Best Practices 3. Supply Chain • • Material and Supplier Qualification - Split Risk-based Management
    9. 9. Quality Excellence Continuous Improvement 1. Relevant Incoming QC Testing • • • 2. Material and Vendor Qualification • 3. Split and implement into Supply Chain Transparency to Tertiary Level • • 4. Every receipt is tested (sampling plan) Type and use Annual trend analysis of incoming receipts Good communication with manufacturers and distributors Successful ACF raw material program Proactive analysis of new requirements • Case Study
    10. 10. Quality Excellence Case 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 nondetectable specification for enteric bacterial organisms 1. Raw Material Supply Chain - 2. Initiated discussions with vendors Analysis of current inventory Environmental Analysis (12-month) - Facilities, equipment, processess and practices
    11. 11. Quality Excellence Case Study Lots Lots w/ Bioburde n Counts Lots w/ Enteric + Lots w/ Bioburden Counts (%) Fermentation 101 23 0 Extraction 15 1 0 6.7% Synthetic 73 9 0 Study Strategy 22.8 % 12.3% Production Method 1. Raw Material Assessment - Production Method - Supplier - Number of Lots 2. Baseline Data - Where to look - Rationale for next steps 3. Directive - Begin routine monitoring Table 3: Raw Material Inventory by Production Method • Table 4: Raw Material Inventory Bioburden – Lots Received Raw materials and EM
    12. 12. Raw Material Program Functionality Quality Group 1. Operational Group Material & Vendor Qualification 1. • Sourcing Strategy • Dual Sourcing • Risk-based Management 2. Change Notification Challenge Supply Chain Implementation • Sourcing Strategy • Dual Sourcing • Risk-based Management 2. Change Notification Must Talk Must Respond Steering Committee Execution
    13. 13. Raw Material Program Steering Committee Manufacturing Operations Technical Support Supply Chain Quality Assurance Quality Control Technical Support Sales and Marketing Best Practices Continuous Improvement Seamless Integration 1. Qualification Requirements 2. Change Notification 3. Incoming QC Testing 1. Customer Requirements 2. Market Trends 1. Supply Chain Implementation 2. Change Notification 3. Relevant Testing
    14. 14. Service Excellence Seamless Integration – Custom Needs 1. Custom Documentation Requirements • 2. Inventory Management • • 3. Raw material documentation Sequestered Inventory - Critical Raw Materials Master Raw Material Lists / Requirements Transparency to Tertiary Level • • Troubleshooting Change Notification
    15. 15. Raw Material Program Conclusion 1. Ensuring Alignment with Industry Expectations • 2. Practical Approach to Our Business • 3. Proactive versus reactive Risk-based management Ensuring Execution • Business Continuity
    16. 16. Acknowledgement Jim Niemeyer Alma Krebs Holden Harris Ashley Werner Tom Fletcher Erik Vaessen Deb Stutz Director of Operations Manager, Supply Chain Manager, Quality Assurance Manager, Quality Control Director, Research & Development EU Territory Business Manager Director, Marketing