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An Effective CMC Strategy is Possible

  • John Geigert
Chapter

Abstract

The two major forces that shape the corporate CMC regulatory compliance strategy for biopharmaceuticals are examined – tolerance of risk and resource allocation. Also, in this chapter, the five key design elements that comprise an effective corporate CMC regulatory compliance strategy for biopharmaceuticals are discussed in detail: (1) align CMC activities with corporate objective, (2) address CMC needs for the specific biopharmaceutical manufacturing process, (3) address CMC needs for the specific biopharmaceutical product, (4) align CMC activities with the strategic ICH guidances, and (5) apply a risk-based CMC regulatory compliance approach during clinical development.

Keywords

Risk tolerance Risk-based approach CMO CTL QbD CQAs CPPs Control strategy 

References

  1. 1.
  2. 2.
    FDA Guidance For Industry – Contract Manufacturing Arrangements for Drugs: Quality Agreements (November 2016); www.fda.gov/downloads/drugs/guidances/ucm353925.pdf
  3. 3.
  4. 4.
    FDA Inspections, Compliance, Enforcement, and Criminal Investigations : Warning Letters – Celltrion Inc. January 26,2 018 – Warning Letter 320–18-28; www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm594395.htm
  5. 5.
    CMC Biotech Working Group – A-Mab: A Case Study in Bioprocess Development (October 30, 2009); CASSS website, cdn.ymaws.com/www.casss.org/resource/resmgr/imported/A-Mab_Case_Study_Version_2-1.pdf
  6. 6.
    FDA Cellular, Tissue, and Gene Therapies Advisory Committee Meeting: Sparks Therapy Briefing Document (October 12, 2017) – Luxturna (Voretigene neparvovec); www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/bloodvaccinesandotherbiologics/cellulartissueandgenetherapiesadvisorycommittee/ucm579300.pdf
  7. 7.
    FDA Consumer Updates: Creating Human Drugs From Genetically Engineered Animals; FDA website, www.fda.gov/ForConsumers/ConsumerUpdates/ucm143980.htm
  8. 8.
    FDA Vaccines, Blood & Biologics: Cellular & Gene Therapy Products – What is Gene Therapy; FDA website, www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm573960.htm
  9. 9.
    EMA Guideline on Immunogenicity Assessment of Therapeutic Proteins (May 2017); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2017/06/WC500228861.pdf
  10. 10.
    EMA Guideline on the Quality of Biologically Active Substances Produced by Stable Transgene Expression in Higher Plants (July 2008); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003154.pdf
  11. 11.
    EMA Guideline on the Quality, Non-Clinical and Clinical Aspects of Gene Therapy Medicinal Products (March 2018); www.ema.europa.eu/documents/scientific-guideline/guideline-quality-non-clinical-clinical-aspects-gene-therapy-medicinal-products_en.pdf
  12. 12.
    A-VAX: Applying Quality By Design to Vaccines – CMC-Vaccines Working Group (May 2012); www.dcvmn.org/IMG/pdf/a-vax-applying-qbd-to-vaccines_2012.pdf
  13. 13.
    ICH Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) (May 2012); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Q11_Step_4.pdf
  14. 14.
    EMA European Public Assessment Report (EPAR): Perjeta (Pertuzumab) (December 2012); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002547/WC500141004.pdf
  15. 15.
    Alt, N., Zhang, T.Y., et.al., Determination of Critical Quality Attributes For Monoclonal Antibodies Using Quality by Design Principles, Biologicals (2016) 44: 291–305Google Scholar
  16. 16.
    Hakemeyer, C., McKnight, N., et.al., Process Characterization and Design Space Definition, Biologicals (2016) 44: 306–318Google Scholar
  17. 17.
    EMA European Public Assessment Report (EPAR): Prolia (Denosumab) (March 2010); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001120/WC500093529.pdf
  18. 18.
    FDA Vaccines, Blood & Biologics: Licensed Products with Supporting Data – Rixubis (Coagulation Factor IX, Recombinant) – Approval History, Letters, Reviews, and Related Documents – Final CMC Review (April 2013); www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm358781.htm
  19. 19.
    Kepert, J.F., Cromwell, M., et. al., Establishing a Control System Using QbD Principles, Biologicals (2016) 44: 319–331CrossRefGoogle Scholar
  20. 20.
    FDA Drug Databases: Drugs@FDA – FDA Approved Drug Products – Gazyva (Obinutuzumab) (November 2013); www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/125486Orig1s000ltr.pdf
  21. 21.
    EMA European Public Assessment Report (EPAR): Gazyvaro (Obinutuzumab) (May 2014); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002799/WC500171596.pdf
  22. 22.
    FDA CDER Manual of Policies & Procedures (MAPP): 5016.1 Applying ICH Q8(R2), Q9 and Q10 Principles to CMC Review (May 2016); www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/default.htm
  23. 23.
    EMA European Public Assessment Report (EPAR): Oxervate (Cenegermin) (May 2017) ; www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004209/WC500232107.pdf
  24. 24.
    EMA European Public Assessment Report (EPAR): Brineura (Cerliponase Alfa) (April 2017) ; www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004065/WC500229800.pdf
  25. 25.
    EMA European Public Assessment Report (EPAR): Hemlibra (Emicizumab) (January 2018) ; www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004406/WC500244745.pdf
  26. 26.
    EMA European Public Assessment Report (EPAR): Shingrix (Herpes Zoster Vaccine, Recombinant, Adjunvanted) (January 2018); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004336/WC500246552.pdf
  27. 27.
    EMA European Public Assessment Report (EPAR): Coagadex (Human Coagulation Factor X) (January 2016) ; www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003855/WC500204191.pdf
  28. 28.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Data – Luxturna (Voretigene Neparvovec-rzyl) – Approval History, Letters, Reviews, and Related Documents – CMC Review (December 2017); www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm589507.htm
  29. 29.
    EMA European Public Assessment Report (EPAR): Zalmoxis (Allogeneic T-Cells Genetically Modified with a Retroviral Vector Encoding for a Truncated Form of the Human Low Affinity Nerve Growth Factor Receptor (ΔLNGFR) and the Herpes Simplex I Virus Thymidine Kinase (HSV-TK Mut2)) (June 2016); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002801/WC500212588.pdf
  30. 30.
    EMA European Public Assessment Report (EPAR) – Withdrawn Applications: Ixinity (Recombinant Coagulation Factor IX) (September 2012) ; www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2013/09/WC500149845.pdf
  31. 31.
    FDA Code of Federal Regulations (CFR) Title 21 Part 312.23 – General Principles of the IND Submission; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=312
  32. 32.
    FDA Guidance for Industry: CGMP for Phase 1 Investigational Drugs (2008); www.fda.gov/downloads/drugs/guidances/ucm070273.pdf
  33. 33.
    FDA (Draft) Guidance Industry: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) (July 2018); www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM610795.pdf
  34. 34.
    EMA Guideline on the Requirements for Quality Documentation Concerning Biological Investigational Medicinal Products in Clinical Trials (September 2018); www.ema.europa.eu/documents/scientific-guideline/guideline-requirements-quality-documentation-concerning-biological-investigational-medicinal_en-0.pdf
  35. 35.
    European Commission – EudraLex the Rules Governing Medicinal Products in the European Union, Volume 4, Good Manufacturing Practice: Guidelines on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products (November 2017); ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf
  36. 36.
    Parenteral Drug Association (PDA) Technical Report No. 56 (Revised 2016): Application of Phase-Appropriate Quality System and cGMP to the Development of Therapeutic Protein Drug Substance (API or Biologic Active Substance); PDA website, www.PDA.org
  37. 37.
    Parenteral Drug Association (PDA) Technical Report (2019): Cell-Based Therapy Control Strategy; PDA website, www.PDA.org
  38. 38.
    EMA Workshop on the Guideline for First-in-Man Clinical Trials For Potentially High-Risk Medicinal Products: TGN 1412 – What Really Happened?; EMA website, www.ema.europa.eu/docs/en_GB/document_library/Presentation/2009/11/WC500010858.pdf
  39. 39.
    National Institutes of Health (NIH) News Release: NIH Suspends Operations in its Clinical Center Pharmaceutical Development Section (June 4, 2015) – FDA Form 483; NIH website, www.cc.nih.gov/phar/pdfs/483.pdf
  40. 40.
    National Institutes of Health (NIH) News Release: Statement on Review of NIH Sterile Production Facilities (April 19, 2016); NIH website, www.nih.gov/news-events/news-releases/statement-review-nih-sterile-production-facilities
  41. 41.
    FDA Guidance for Industry: Expedited Programs for Serious Conditions – Drugs and Biologics (May 2014); www.fda.gov/downloads/Drugs/Guidances/UCM358301.pdf
  42. 42.
    FDA Drug Databases: Drugs@FDA – FDA Approved Drug Products – Darzalex (Daratumumab) – CDER Memorandum of Meeting Minutes – Breakthrough Therapy Daratumumab (Janssen Biotech) (July 31, 2013); www.accessdata.fda.gov/drugsatfda_docs/nda/2015/761036Orig1s000Admincorres.pdf
  43. 43.
    EMA European Medicines Agency Guidance on Interactions in the Context of PRIME (May 2018); www.ema.europa.eu/docs/en_GB/document_library/Other/2018/05/WC500248826.pdf
  44. 44.
    FDA Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (April 2015); www.fda.gov/downloads/drugs/guidances/ucm291128.pdf
  45. 45.
    FDA Speeches by FDA Officials: Remarks by Commissioner Gottlieb to the Alliance for Regenerative Medicine’s Annual Board Meeting (May 22, 2018); www.fda.gov/NewsEvents/Speeches/ucm608445.htm

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • John Geigert
    • 1
  1. 1.BioPharmaceutical Quality SolutionsCarlsbadUSA

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