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The Challenge of CMC Regulatory Compliance for Biopharmaceuticals pp 287–310Cite as

Priceless Potency (Therapeutic Activity)

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Abstract

The complexity of biopharmaceuticals can present significant challenges to establishing potency. In this chapter, the three types of functional activity assays for measuring potency of biopharmaceuticals will be examined: bioassay, surrogate assay, and assay matrix. In addition, it will be shown that the development, optimization, and validation of these potency assays can be implemented by a risk-based approach during clinical development. Finally, it will be stressed that most manufacturers underestimate the amount of resources and time needed to properly implement these potency assays for recombinant proteins, monoclonal antibodies, genetically engineered viruses and cells.

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References

  1. Code of Federal Regulations Title 21 Food and Drugs: Part 211 – Definitions; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211

  2. EC Directive 2001/83/EC of the European Parliament and Council, Concerning Community Code Relating to Medicinal Products For Human Use; ec.europa.eu/health/files/eudralex/vol-1/dir_2001_83_cons2009/2001_83_cons2009_en.pdf

  3. Code of Federal Regulations Title 21 Food and Drugs: Part 210.3 – Definitions; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=210.3

  4. Code of Federal Regulations Title 21 Food and Drugs: Part 600.3 – Definitions; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=600.3

  5. Code of Federal Regulations Title 21 Food and Drugs: Part 610.10 – Potency; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=610.10

  6. ICH Q6B Specifications: Test Procedures and Acceptance Criteria For Biotechnological/Biological Products (March 1999); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6B/Step4/Q6B_Guideline.pdf

  7. EMA Guideline on Potency Testing of Cell Based Immunotherapy Medicinal Products for the Treatment of Cancer (July 2016); www.ema.europa.eu/documents/scientific-guideline/guideline-potency-testing-cell-based-immunotherapy-medicinal-products-treatment-cancer-revision-1_en.pdf

  8. EMA Guideline on Development, Production, Characterisation and Specification for Monoclonal Antibodies and Related Products (July 2016); www.ema.europa.eu/documents/scientific-guideline/guideline-development-production-characterisation-specification-monoclonal-antibodies-related_en.pdf

  9. 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

  10. EMA Guideline on the Quality, Non-clinical and Clinical Aspects of Medicinal Products Containing Genetically Modified Cells (July 2018); www.ema.europa.eu/documents/scientific-guideline/draft-guideline-quality-non-clinical-clinical-aspects-medicinal-products-containing-genetically_en.pdf

  11. ICH Q5C Stability Testing of Biotechnological/Biological Products (November 1995); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5C/Step4/Q5C_Guideline.pdf

  12. ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process (November 2004); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5E/Step4/Q5E_Guideline.pdf

  13. FDA Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (April 2015); www.fda.gov/downloads/drugs/guidances/ucm291128.pdf

  14. FDA Guidance For Industry: Potency Tests For Cellular and Gene Therapy Products (January 2011); www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM243392.pdf

  15. United States Pharmacopeia (USP), website www.usp.org; European Pharmacopeia (Ph. Eur.), website www.edqm.eu

  16. United States Pharmacopeia (USP): <1032> Design and Development of Biological Assays, <1033> Biological Assay Validation, <1034> Analysis of Biological Assays; website www.usp.org

  17. FDA Advisory Committee Meetings – Meeting of the Arthritis Advisory Committee: Inflectra (Inflixumab, Biosimilar Remicade) – FDA Advisory Committee Briefing Document Prepared by the FDA (February 09, 2016); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM484859.pdf

  18. FDA Advisory Committee Meetings – Meeting of the Oncology Drugs Advisory Committee: Amgen Mvasi (Bevacizumab, Biosimilar Avastin) – FDA Advisory Committee Briefing Document Prepared by the FDA (July 13, 2017); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566365.pdf

  19. FDA Advisory Committee Meetings – Meeting of the Oncology Drugs Advisory Committee: Amgen Mvasi (Bevacizumab, Biosimilar Avastin) – FDA Advisory Committee Briefing Document Prepared by Amgen (July 13, 2017); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566367.pdf

  20. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Imfinzi (Durvalumab): Approval History, Letters, Reviews and Related Documents – CMC Review – Office of Pharmaceutical Quality Integrated Review (March 06, 2017); www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761069Orig1s000ChemR.pdf

  21. EMA European Public Assessment Report (EPAR): Mepsevii (Vestronidase Alfa) (June 2018); www.ema.europa.eu/documents/assessment-report/mepsevii-epar-public-assessment-report_en.pdf

  22. FDA Advisory Committee Meetings – Meeting of the Oncology Drugs Advisory Committee: Novartis Kymriah (Tisagenlecleucel) – FDA Advisory Committee Briefing Document Prepared by the FDA (July 12, 2017); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566166.pdf

  23. FDA Advisory Committee Meetings – Meeting of the Oncology Drugs Advisory Committee: Celltrion CT-P10 (Rituximab, Biosimilar to Rituxan) – FDA Advisory Committee Briefing Document Prepared by Celltrion (October 10, 2018); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM622647.pdf

  24. FDA Advisory Committee Meetings – Meeting of the Oncology Drugs Advisory Committee: Celltrion CT-P10 (Rituximab, Biosimilar to Rituxan) – FDA Advisory Committee Briefing Document Prepared by the FDA (October 10, 2018); www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM622649.pdf

  25. EMA European Public Assessment Report (EPAR): Strensiq (Asfotase Alfa) (June 2015); www.ema.europa.eu/documents/assessment-report/strensiq-epar-public-assessment-report_en.pdf

  26. EMA European Public Assessment Report (EPAR): Imlygic (Talimogene Laherparepvec) (October 2015); www.ema.europa.eu/documents/assessment-report/imlygic-epar-public-assessment-report_en.pdf

  27. EMA European Public Assessment Report (EPAR): Strimvelis (Autologous CD34+ Enriched Cell Fraction) (April 2016); www.ema.europa.eu/documents/assessment-report/strimvelis-epar-public-assessment-report_en.pdf

  28. EMA European Public Assessment Report (EPAR): Kymriah (Tisagenlecleucel) (June 2018); www.ema.europa.eu/documents/assessment-report/kymriah-epar-public-assessment-report_en.pdf

  29. EMA European Public Assessment Report (EPAR): Yescarta (Axicabtagene Ciloleucel) (June 2018); www.ema.europa.eu/documents/assessment-report/yescarta-epar-public-assessment-report_en.pdf

  30. 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

  31. European Commission (EC) 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

  32. FDA (Draft) Guidance for 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

  33. Code of Federal Regulations Title 21 Food and Drugs: Part 312.23 – IND Content and Format; www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.23

  34. FDA Guidance for Industry: For the Submission of Chemistry, Manufacturing, and Controls Information for a Therapeutic Recombinant DNA-Derived Product or a Monoclonal Antibody Product for In Vivo Use (August 1996); www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/general/ucm173477.pdf

  35. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Crysvita (Burosumab-twza): Approval History, Letters, Reviews and Related Documents – Administrative and Correspondence Documents – Mid-Cycle Communication Meeting (November 30, 2017); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761068Orig1s000Admincones.pdf

  36. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Crysvita (Burosumab-twza): FDA Market Approval Letter (April 17, 2018); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761068Orig1s000Approv.pdf

  37. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Oxervate (Cenegermin-bkbj): Approval History, Letters, Reviews and Related Documents – CMC Review – Executive Summary (August 07, 2018); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761094Orig1s000ChemR.pdf

  38. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Oxervate (Cenegermin-bkbj): FDA Market Approval Letter (August 22, 2018); www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/761094Orig1s000Ltr.pdf

  39. EMA European Withdrawal Assessment Report (EPAR): Fulphia (Pegfilgrastim, Biosimilar of Neulasta) (October 2016); www.ema.europa.eu/documents/withdrawal-report/withdrawal-assessment-report-fulphila_en.pdf

  40. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Ocrevus (Ocrelizumab): Approval History, Letters, Reviews and Related Documents – CMC Review – Executive Summary (March 20, 2017); www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761053Orig1s000ChemR.pdf

  41. FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Ocrevus (Ocrelizumab): FDA Market Approval Letter (April 28, 2017); www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761053Orig1s000ltr.pdf

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Authors and Affiliations

  1. BioPharmaceutical Quality Solutions, Carlsbad, CA, USA

    John Geigert

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  1. John Geigert
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Geigert, J. (2019). Priceless Potency (Therapeutic Activity). In: The Challenge of CMC Regulatory Compliance for Biopharmaceuticals . Springer, Cham. https://doi.org/10.1007/978-3-030-13754-0_10

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