"The greater our knowledge increases, the more our ignorance unfolds. " U. S. President John F. Kennedy, speech, Rice University, September 12, 1962 My primary purpose for writing this book was much more than to provide another information source on Chemistry, Manufacturing & Controls (CMC) that would rapidly become out of date. My primary purpose was to provide insight and practical suggestions into a common sense business approach to manage the CMC regulatory compliance requirements for biopharmaceuticals. Such a common sense business approach would need (1) to be applicable for all types of biopharmaceutical products both present and future, (2) to address the needs of a biopharmaceutical manufacturer from the beginning to the end of the clinical development stages and including post market approval, and (3) to be adaptable to the constantly changing CMC regulatory compliance requirements and guidance. Trying to accomplish this task was a humbling experience for this author! In Chapter 1, the CMC regulatory process is explained, the breadth of products included under the umbrella ofbiopharmaceuticals are identified, and the track record for the pharmaceutical and biopharmaceutical industry in meeting CMC regulatory compliance is discussed. In Chapter 2, while there are many CMC commonalities between biopharmaceuticals and chemically-synthesized pharmaceuticals, the significant differences in the way the regulatory agencies handle them are examined and the reasons for why such differences are necessary is discussed. Also, the importance of CMC FDA is stressed.
Auflage
Sprache
Verlagsort
Verlagsgruppe
Springer Science+Business Media
Zielgruppe
Für Beruf und Forschung
Für höhere Schule und Studium
Research
Illustrationen
Maße
Höhe: 260 mm
Breite: 183 mm
Dicke: 25 mm
Gewicht
ISBN-13
978-0-306-48040-9 (9780306480409)
DOI
10.1007/978-1-4419-9131-7
Schweitzer Klassifikation
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.
