The Challenge of CMC Regulatory Compliance for Biopharmaceuticals

1 Biopharmaceutical CMC Regulatory Compliance: What is It?.- 1. Defining Our Terms.- 2. Under the Biopharmaceutical Umbrella.- 3. Regulatory Development of Biopharmaceuticals.- 4. CMC Regulatory Compliance Track Record.- 2 Are Biopharmaceuticals Really Different?.- 1. Perception or Reality.- 2. Regulatory Agencies Speak.- 3. Three Unique CMC Challenges for Biopharmaceuticals.- 4. CMC Meetings with the FDA Take on Greater Importance.- 5. What About CMC Meetings with Emea.- 6. Biopharmaceuticals Need to be Treated Differently.- 3 Developing the Corporate CMC Regulatory Compliance Strateg.- 1. Three Key Elements for a Complete CMC Strategy.- 2. The Minimum CMC Continuum.- 3. Minimum CMC Requirements for Clinical Development.- 4. Full Cmc Requirements For Dossier Filing.- 5. ‘Case-by-Case’ CMC Strategy Specifics.- 4 Can’t Ignore cGMP.- 1. Not Optional.- 2. GMPS for Everything.- 3. Where in the Manufacturing Process Should GMP Begin.- 4. When During Clinical Development Should GMP Begin.- 5. Consequences of not Following GMPS.- 6. Strategic CMC Tips for GMP Compliance.- 5 Recombinant Source Material: Master/Working Bank.- 1. Needed: Reliable, Continuous, Stable Genetic Source.- 2. So Many Hosts to Choose From.- 3. CMC Guidance on Preparation of a Bank.- 4. CMC Guidance on Characterization of a Bank.- 5. A Successful CMC Strategy for Banks.- 6 Production: Expansion of the Recombinant Organism and Expression of the Biopharmaceutica.- 1. Goals: Identity, Capacity and Consistency.- 2. Adequate Description of the Production Process.- 3. Validation of a Cell-Based Production Process.- 4. Additional Production Controls and Concerns.- 5. What Can Go Wrong.- 6. Strategic CMC Tips For Production.- 7 Purification of the Biopharmaceutical.- 1. Goals: Purity, Recovery andConsistency.- 2. Adequate Description of the Purification Process.- 3. Facility and Utility Concerns.- 4. Purification Process Validation.- 5. In-Process Controls.- 6. Process-Related Impurity Profile.- 7. Viral Safety Evaluation.- 8. Purification Controls for Gene Therapy Processes.- 9. What Can Go Wrong.- 8 Biopharmaceutical Drug Product Manufacturing.- 1. Three Basic CMC Regulatory Concerns.- 2. Formulation of a Biopharmaceutical.- 3. Biopharmaceutial Manufacturing Processes.- 4. Adequate Description of the Manufacturing Process.- 5. Adequate Control Over the Manufacturing Process.- 6. What Can Go Wrong.- 7. Strategic CMC Tips for Drug Product Manufacturing.- 9 Physicochemical/Biological Analysis of the Biopharmaceutical Produc.- 1. A Challenging Analysis.- 2. Unraveling the Molecular Properties.- 3. Characterization of Biopharmaceuticals.- 4. Release Testing and Specifications.- 5. Biopharmaceutical Stability and Expiration Dating.- 6. What Can Go Wrong.- 7. Strategic Cmc Tips For Biopharmaceutical Analysis.- 10 Managing Process Changes — Demonstrating Product Comparabilit.- 1. Not As Easy as it Seems.- 2. Regulatory Management of Process Changes.- 3. Demonstrating Product Comparability.- 4. Comparability Protocols.- 5. Case Examples of Biopharmaceutical Comparability.- 11 Biopharmaceutical CMC Outsourcing.- 1. Regulatory Expectations for Contracted Works.- 2. Developing the Intercompany Quality Agreement.- 3. Strategic CMC Tips for Outsourcing.- 12 Concluding Thoughts on Biopharmaceutical CMC Regulatory Compliance.- 1. Most Helpful Websites for Biopharmaceuticals.- 2. Website Resources from FDA.- 3. Resources from Emea.- 4. Resources from Professional Associations.- 5. Conclusion.- References.