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Demonstrating Product Comparability After Process Changes

  • John Geigert
Chapter

Abstract

Manufacturers need the freedom to make changes for improving their biopharmaceutical processes, not only during clinical development but also for continuous process improvement once in the marketplace. But along with this freedom to make manufacturing process changes comes the responsibility of carefully assessing the potential safety and efficacy impact on the biopharmaceutical product due to the changes being implemented. Demonstrating product comparability for a biopharmaceutical after a manufacturing process change is no easy task, whether it be for a recombinant protein or a genetically engineered cell. The three key elements of an effective comparability study will be examined: (1) the level of risk by type of process change, (2) stepwise reduction of residual risk, and (3) a risk-based effort by stage of clinical development. In this chapter, the difference between a comparability study and a comparability contract will be examined. Also, the challenge for biosimilar manufacturers in confirming biosimilarity will be discussed.

Keywords

Highly similar Comparability exercise Comparability contract PACMP Biosimilarity Interchangeability 

References

  1. 1.
    EMA European Public Assessment Report (EPAR): Shingrix (Herpes Zoster Vaccine, Recombinant, Adjuvanted) (January 2018); www.ema.europa.eu/documents/assessment-report/shingrix-epar-public-assessment-report_en.pdf
  2. 2.
    EMA European Public Assessment Report (EPAR): Ilumetri (Tildrakizumab) (July 2018); www.ema.europa.eu/documents/assessment-report/ilumetri-epar-public-assessment-report_en.pdf
  3. 3.
    EMA European Public Assessment Report (EPAR): Bavencio (Avelumab) (July 2017); www.ema.europa.eu/documents/assessment-report/bavencio-epar-public-assessment-report_en.pdf
  4. 4.
    Vezer, B., Buzas, Z., et.al., Authorized Manufacturing Changes for Therapeutic Monoclonal Antibodies (mAbs) in European Public Assessment Report (EPAR) Documents; Curr Med Res Opin (2016), 32: 829–834CrossRefGoogle Scholar
  5. 5.
    Tebbey, P. W., Varga, A., et.al., Consistency of Quality Attributes for the Glycosylated Monoclonal Antibody Humira® (Adalimumab); MAbs (2015), 805–811CrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    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
  8. 8.
    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
  9. 9.
    FDA (Draft) Guidance for Industry: Comparability Protocols for Human Drugs and Biologics – Chemistry, Manufacturing and Controls Information (April 2016); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM496611.pdf
  10. 10.
    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
  11. 11.
    FDA Guidance for Industry: Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products (July 1997); www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm124805.pdf
  12. 12.
    World Health Organization (WHO) Guidelines on Procedures and Data Requirements for Changes to Approved Biotherapeutic Products (October 2017); www.who.int/biologicals/expert_committee/PAC_highlighted_20_Oct_2017.HK.IK.pdf
  13. 13.
    FDA (Draft) Guidance for Industry: Chemistry, Manufacturing, and Controls Changes to an Approved Application – Certain Biological Products (December 2017); www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/general/ucm590118.pdf
  14. 14.
    EC Variations Guideline: Guidelines on the Details of the Various Categories of Variations, on the Operation of the Procedures Laid Down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 Concerning the Examination of Variations to the Terms of Marketing Authorisations for Medicinal Products for Human Use and Veterinary Medicinal Products and on the Documentation to be Submitted Pursuant to Those Procedures (May 16, 2013); https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-2/c_2013_2008/c_2013_2008_doc/c_2013_2804_en.doc
  15. 15.
    FDA Inspections, Compliance, Enforcement, and Criminal Investigations – Warning Letters: Porton Biopharma (January 19, 2017); www.fda.gov/iceci/enforcementactions/warningletters/2017/ucm538105.htm
  16. 16.
    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
  17. 17.
    FDA (Draft) Guidance for Industry: Formal Meeting Between the FDA and Sponsors or Applicants of PDUFA Products (December 2017); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM590547.pdf
  18. 18.
    EMA European Public Assessment Report (EPAR): Oxervate (Cenegermin) (May 2017); www.ema.europa.eu/documents/assessment-report/oxervate-epar-public-assessment-report_en.pdf
  19. 19.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Data – Andexxa (Recombinant Coagulation Factor Xa, Inactivated-zhzo) – Approval History, Letters, Reviews and Related Documents – An Addendum to CMC Review (17 August 2016) of Portola’s BLA for Coagulation Factor Xa (Recombinant), Inactivated [ANDEXXA] & Review of Portola’s 3 August 2017 Responses to the Complete Response Letter (August 17, 2017); www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm606681.htm
  20. 20.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Data – Andexxa (Recombinant Coagulation Factor Xa, Inactivated-zhzo) – Approval History, Letters, Reviews and Related Documents – BLA Complete Response Letter (August 17, 2016); www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm606681.htm
  21. 21.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Data – Andexxa (Recombinant Coagulation Factor Xa, Inactivated-zhzo) – Approval History, Letters, Reviews and Related Documents – October 27, 2016 Type A Meeting Summary (November 25, 2016); www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm606681.htm
  22. 22.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Vimizim (Elosulfase Alfa): Approval History, Letters, Reviews and Related Documents – Other Reviews – Memorandum of Meeting Minutes (September 27, 2013); www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125460Orig1s000OtherR.pdf
  23. 23.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Vimizim (Elosulfase Alfa): Approval History, Letters, Reviews and Related Documents – Administrative and Correspondence Documents – Late-Cycle Meeting Background Package (November 04, 2013); www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125460Orig1s000AdminCorres.pdf
  24. 24.
    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/documents/assessment-report/zalmoxis-epar-public-assessment-report_en.pdf
  25. 25.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Data – Kymriah (Tisagenlecleucel) – Summary Basis for Regulatory Action (August 30, 2017); www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM606836.pdf
  26. 26.
    FDA (Draft) Guidance for Industry: Comparability Protocols for Human Drugs and Biologics – Chemistry, Manufacturing, and Controls Information (April 2016); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM496611.pdf
  27. 27.
    ICH Q12 (Step 2) Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Core Guideline (November 2017); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q12/Q12_DraftGuideline_Step2_2017_1116.pdf
  28. 28.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Libtayo (Cemiplimab-rwlc): Approval History, Letters, Reviews and Related Documents –Chemistry Review(s) – Product Quality Review (September 27, 2018); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761097Orig1s000ChemR.pdf
  29. 29.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Ilumya (Tildrakizumab-asmn): Approval History, Letters, Reviews and Related Documents – Chemistry Review(s) – Product Quality Review (November 10, 2017); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761067Orig1s000ChemR.pdf
  30. 30.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Palynziq (Pegvaliase-pqpz): Approval History, Letters, Reviews and Related Documents – Chemistry Review(s) – Quality Review (May 21, 2018); www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761079Orig1s000ChemR.pdf
  31. 31.
    EMA European Public Assessment Report (EPAR): Lamzede (Velmanase Alfa) (January 2018); www.ema.europa.eu/documents/assessment-report/lamzede-epar-public-assessment-report_en.pdf
  32. 32.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Mepsevii (Vestronidase Alfa-vjbk): Approval History, Letters, Reviews and Related Documents – Chemistry Review(s) – OBP CMC Review Data Sheet (August 14, 2017); www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761047Orig1s000ChemR.pdf
  33. 33.
    EMA European Public Assessment Report (EPAR): Aimovig (Erenumab) (May 2018); www.ema.europa.eu/documents/assessment-report/aimovig-epar-public-assessment-report_en.pdf
  34. 34.
    EMA European Public Assessment Report (EPAR): Kymriah (Tisagenlecleucel) (June 2018); www.ema.europa.eu/documents/assessment-report/kymriah-epar-public-assessment-report_en.pdf
  35. 35.
    FDA (Draft) Guidance for Industry: New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2) (December 2018); www.fda.gov/downloads/drugs/guidances/ucm273001.pdf
  36. 36.
    FDA Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (April 2015); www.fda.gov/downloads/drugs/guidances/ucm291128.pdf
  37. 37.
    EMA Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance – Quality Issues (Revision 1) (May 2014); www.ema.europa.eu/documents/scientific-guideline/guideline-similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active_en-0.pdf
  38. 38.
    FDA Guidance for Industry: Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product (April 2015); www.fda.gov/downloads/drugs/guidances/ucm291134.pdf
  39. 39.
    FDA Drugs – Search Drugs@FDA – FDA Approved Drug Products: Amjevita (Adalimumab-atto, Biosimilar of Humira): Approval History, Letters, Reviews and Related Documents – Chemistry Review(s) – OBP CMC Review Data Sheet (August 15, 2016); www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024Orig1s000ChemR.pdf
  40. 40.
    EMA Reflection Paper on Statistical methodology for the Comparative Assessment of Quality Attributes in Drug Development (March 2017); www.ema.europa.eu/documents/scientific-guideline/draft-reflection-paper-statistical-methodology-comparative-assessment-quality-attributes-drug_en.pdf
  41. 41.
    EMA European Public Assessment Report (EPAR): Mvasi (Bevacizumab, Biosimilar of Avastin) (January 2018); www.ema.europa.eu/documents/assessment-report/mvasi-epar-public-assessment-report_en.pdf

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

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

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