Ancillary Materials in Cell Therapy Product Development PDF
Preview Ancillary Materials in Cell Therapy Product Development
Ancillary Materials in Cell Therapy Product Development Nicole M. Provost, PhD Independent Consultant Member of USP BB2 Expert Committee Ancillary Material Topics to be Covered Common Sense Approaches Definitions and Abbreviations CMO Advantages and Disadvantages Risk-based Approaches “Big 3” Questions to Address Relevant Examples Take-home Messages (Intuitively Obvious ) Common Sense Approaches Figure out what you know, don’t know Don’t ignore problems Make plans Be ready to change your plans Definitions and Abbreviations Ancillary Material (“AM”) ◦ Material used and removed during manufacture of a cell or tissue product Supplier ◦ “Off-the-shelf” manufacturer of AM Contract Manufacturing Organization (“CMO”) ◦ Custom manufacturer of AM Product Development (“PD”) Research and Development (“R&D”) CMO Advantages AM Manufactured by CMO ◦ No Manufacturing and Quality personnel to hire and oversee ◦ Reduced need for additional facilities ◦ Reduced need for additional headcount Supply Chain Managed by CMO ◦ Fewer suppliers to oversee ◦ Shipping and storage managed by CMO ◦ Multiple suppliers = more flexibility CMO Disadvantages AM Manufactured by CMO ◦ Ultimately, CMO issues become yours ◦ Be prepared to troubleshoot ◦ Designate a contact person on your side Supply Chain Managed by CMO ◦ Sourcing is out of your control ◦ Shipping and storage issues can disrupt your own manufacturing and R&D ◦ Multiple suppliers may = more variability Risk-based Approaches to AMs in a Nutshell Perform Criticality Assessments Identify the major risks to cell product: purity, consistency, supply, stability, etc. Determine AM & product failure mode(s) Define product/patient impacts Mitigate or eliminate the major risks Decide which headaches you own, and which you share with the CMO Build trust with your CMO The “Big 3” Questions for PD What’s in the Ancillary Material? How does the Ancillary Material affect the cell product? • Can the CMO make enough Ancillary Material? What’s in the Ancillary Material? Is it a complex mixture? ◦ Classic examples: culture media and serum Identify & characterize active component(s) ◦ Sometimes the impurities are active! ◦ Conduct fractionation and add-back experiments ◦ Relative component ratios may be important Identify major impurities ◦ Common examples: fragments, endotoxin, DNA How variable are the batches? ◦ Quantitation and characterization assays critical How Does the AM Affect the Cell Product? Is the AM essential to cell product quality? ◦ Damage or omit the AM to assess its criticality ◦ Determine concentration effects, stability in use ◦ Assess many batches or sources Do impurities affect cell product quality? ◦ Add-back experiments with known impurities ◦ Determine safety limits Are both AM and impurities removed during cell product manufacturing? ◦ Both can be washed out, taken up by cells, or adsorbed onto production equipment
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