Advertisement

Challenge of Adventitious Agent Control

  • John Geigert
Chapter

Abstract

The primary adventitious agents of concern for biologicals are examined in detail – the prions, viruses, mycoplasmas, and bacteria/fungi microbes. The three major complementary approaches for control of these contaminating agents – barriers to entry, testing to confirm absence, and inactivation/removal – are discussed. Risk control examples are provided for animal-derived materials used in biological manufacturing, cell culture manufacturing processes of biopharmaceuticals, transgenic-produced biopharmaceuticals, human plasma-derived proteins, virus-based biologics, and cell-based biologics. In addition, lessons learned from previously reported infectious agent contaminations of biologics are presented. Finally, some CMC strategic tips are provided for minimizing the overall risk of adventitious agent contamination of biopharmaceuticals.

Keywords

Adventitious agent Prion Virus Mycoplasma Bacteria/Fungi Risk-based NAT RMM 

References

  1. 1.
    World Health Organization (WHO) Regulatory Risk Assessment in the Case of Adventitious Agent Finding in a Marketed Vaccine: Scientific Principles to Consider (2013); www.who.int/biologicals/WHO_Risk_Assessment_1st_public_consultation_12_March_2013.pdf
  2. 2.
  3. 3.
    Centers for Disease Control and Prevention (CDC): Prion Diseases; CDC website, www.cdc.gov/prions/index.html
  4. 4.
    Wickner, R.B., Yeast and Fungal Proteins, Cold Spring Harb Perspect Biol (2016); pdfs.semanticscholar.org/550a/dcd7c90ba03f47b05b6d108ed0eb879fa565.pdf
  5. 5.
    FDA Drugs: Celebrating a Milestone: FDA’s Approval of First Genetically-Engineered Product (2007); www.fda.gov/downloads/aboutfda/history/productregulation/ucm593496.pdf
  6. 6.
    FDA Guidance for Industry: Amendment to Guidance For Industry: Revised Preventative Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products (January 2016); www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/blood/ucm307137.pdf
  7. 7.
    FDA Vaccines, Blood & Biologics: Donating Blood Questions and Answers; FDA website, www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/questionsaboutblood/donatingblood/default.htm
  8. 8.
    EMA CHMP/CAT Position Statement on Creutzfeldt-Jakob Disease and Advanced Therapy Medicinal Products (June 2011); www.ema.europa.eu/docs/en_GB/document_library/Position_statement/2011/06/WC500108069.pdf
  9. 9.
    EMA Guideline on the Quality of Biological Active Substances Produced by Transgenic Animals (May 2013); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/06/WC500144136.pdf
  10. 10.
    EMA European Public Assessment Report (EPAR): Strensiq (Recombinant Asfotase Alfa) (June 2015); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003794/WC500194340.pdf
  11. 11.
    EMA European Public Assessment Report (EPAR): Lartruvo (Olaratumab) (September 2016); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004216/WC500216871.pdf
  12. 12.
    EMA European Public Assessment Report (EPAR): Shingrix (Herpes Zoster Vaccine, Recombinant, Adjuvanted) (January 2018); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004336/WC500246552.pdf
  13. 13.
    EMA European Public Assessment Report (EPAR): Strimvelis (Autologous CD34+ Cells Transduced With a Retroviral Vector That Encodes for the Human ADA cDNA Sequence) (April 2016); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003854/WC500208201.pdf
  14. 14.
    European Directorate for the Quality of Medicines & Healthcare (EDQM): European Pharmacopeia 5.2.8 – Minimizing the Risk of Transmitting Animal Spongiform Encephalopathy Agents Via Human and Veterinary Medicinal Products (Chapter Identical to Note for Guidance on Minimizing the Risk of Transmitting Animal Spongiform Encephalopathy Agents Via Human and Veterinary Medicinal Products – Revision 3, EMA/410/01 rev.3); EDQM website, European Pharmacopeia (Ph.Eur.)Google Scholar
  15. 15.
    European Directorate for the Quality of Medicines & Healthcare (EDQM): Certification of Suitability – Background and Legal Framework; EDQM website, www.edqm.eu/en/certification-background-77.html
  16. 16.
    European Directorate for the Quality of Medicines & Healthcare (EDQM): TSE Certification Database; EDQM website, extranet.edqm.eu/publications/recherches_CEP.shtml
  17. 17.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – BOTOX – Package Insert (May 2018); www.accessdata.fda.gov/drugsatfda_docs/label/2018/103000s5306lbl.pdf
  18. 18.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Yescarta (Axicabtagene Ciloleucel) – Package Insert (2017); www.fda.gov/downloads/biologicsbloodvaccines/cellulargenetherapyproducts/approvedproducts/ucm581226.pdf
  19. 19.
    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
  20. 20.
    EMA CHMP Position Statement on Creutzfeldt-Jakob Disease and Plasma-Derived and Urine-Derived Medicinal Products (June 2011); www.ema.europa.eu/docs/en_GB/document_library/Position_statement/2011/06/WC500108071.pdf
  21. 21.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Panzyga (Immune Globulin Subcutaneous, Human) – Package Insert (2018); www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM615706.pdf
  22. 22.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Carimune NF Nanofiltered (Immune Globulin Intravenous, Human) – Package Insert (2013); www.fda.gov/downloads/BiologicsBloodVaccines/UCM152763.pdf
  23. 23.
    EMA European Public Assessment Report (EPAR): Ruconest (Recombinant Conestat Alfa) (June 2010); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001223/WC500098546.pdf
  24. 24.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – ATryn (Recombinant Antithrobin) – Package Insert (2009); www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM134045.pdf
  25. 25.
    FDA Vaccines, Blood &Biologics: Recommendations for the Use of Vaccines Manufactured with Bovine-Derived Materials; CBER website, www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm111476.htm
  26. 26.
    EMA Statement on the Evaluation of Bovine Spongiform Encephalopathies (BSE)-Risk Via the Use of Materials of Bovine Origin in or During the Manufacture of Vaccines (February 2001); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003717.pdf
  27. 27.
    National Hemophila Foundation (NHF): History of Bleeding Disorders; NHF website, www.hemophilia.org/Bleeding-Disorders/History-of-Bleeding-Disorders
  28. 28.
    EMA Questions and Answers on the Review of Rotarix (Rotavirus Vaccine, Live) (July 2010); www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2010/07/WC500094832.pdf
  29. 29.
    EMA Questions and Answers on the Review of RotaTeq (Rotavirus Vaccine, Live, Oral) (September 2010); www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2010/09/WC500097001.pdf
  30. 30.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Hyqvia (Immune Globulin Infusion Human) – Package Insert (2014); www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM414440.pdf
  31. 31.
    EMA Guideline on the Use of Bovine Serum in the Manufacture of Human Biological Medicinal Products (May 2013); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/06/WC500143930.pdf
  32. 32.
    EMA Guideline on the Use of Porcine Trypsin Used in the Manufacture of Human Biological Medicinal Products (February 2014); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/02/WC500162147.pdf
  33. 33.
    FDA Guidance for Industry: Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications (February 2010); www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vaccines/ucm202439.pdf
  34. 34.
    ICH Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin (September 1999); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5A_R1/Step4/Q5A_R1__Guideline.pdf
  35. 35.
    World Health Organization (WHO) Recommendations for the Evaluation of Animal Cell Cultures as Substrates for the Manufacture of Biological Medicinal Products and for the Characterization of Cell Banks – Replacement of Annex 1 of WHO Technical Report Series, No. 878 (2013); www.who.int/biologicals/expert_committee/TRS_978_61st_report.pdf
  36. 36.
    Kerr, A. and Nims, R., Adventitious Viruses Detected in Biopharmaceutical Bulk Harvest Samples Over a 10-Year Period; PDA Journal website, PDA J Pharm Sci and Technol (2010), 64(5): 481–485Google Scholar
  37. 37.
    Kiss, R.D., Practicing Safe Cell Culture: Applied Process Designs for Minimizing Virus Contamination Risk; PDA Journal website, PDA J Pharm Sci and Technol (2011), 65(6): 715–729CrossRefGoogle Scholar
  38. 38.
    Skrine, J., A Biotech Production Facility Contamination Case Study - Minute Mouse Virus; PDA Journal website, PDA J Pharm Sci and Technol (2011), 65(6): 599–611CrossRefGoogle Scholar
  39. 39.
    Moody, M., Washington, A., et.al., Mouse Minute Virus Contamination (MMV) - A Case Study: Detection, Root Cause Determination, and Corrective Actions; PDA Journal website, PDA J Pharm Sci and Technol (2011), 65: 580–588Google Scholar
  40. 40.
    Genzyme Press Release: Genzyme Temporarily Interrupts Production at Allston Plant (June 16, 2009); Sanofi Genzyme website, www.sanofigenzyme.com
  41. 41.
    Rubino, M.J., Experiences with HEK293: A Human Cell Line; PDA Journal website, PDA J Pharm Sci and Technol (2010), 64(5): 392–395Google Scholar
  42. 42.
    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
  43. 43.
    EMA European Public Assessment Report (EPAR): Fasenra (Benralizumab) (November 2017); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004433/WC500245333.pdf
  44. 44.
    EMA European Public Assessment Report (EPAR): Qarziba (Dinutuximab Beta) (March 2017; www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003918/WC500227726.pdf
  45. 45.
    EMA European Public Assessment Report (EPAR): Amgevita (Adalimumab) (January 2017); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004212/WC500225277.pdf
  46. 46.
    EMA Guideline on Virus Safety Evaluation of Biotechnological Investigational Medicinal Products (2008); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003795.pdf
  47. 47.
    FDA Guidance For Industry: Process Validation – General Principles and Practices (January 2011); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070336.pdf
  48. 48.
    The Big Picture Book of Viruses; Virology.net website, www.virology.net/Big_Virology/BVHomePage.html
  49. 49.
    EMA European Public Assessment Report (EPAR): Fulphila (Recombinant Pegfilgrastrim, Biosimilar to Neulasta) (2018); www.ema.europa.eu/documents/assessment-report/fulphila-public-assessment-report_en.pdf
  50. 50.
    EMA European Public Assessment Report (EPAR): Terrosa (Recombinant Teriparatide) (2016); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003916/WC500223889.pdf
  51. 51.
    EMA European Public Assessment Report (EPAR): Nplate (Romiplostim Recombinant Fusion Protein) (2008); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/000942/WC500039475.pdf
  52. 52.
    EMA European Public Assessment Report (EPAR): Lucentis (Ranibizumab Monoclonal Antibody Fragment) (2007); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000715/WC500043550.pdf
  53. 53.
    EMA European Public Assessment Report (EPAR): Semglee (Recombinant Insulin Glargine) (2018); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004280/WC500249349.pdf
  54. 54.
    EMA European Public Assessment Report (EPAR): Levemir (Recombinant Insulin Detemir) (2004); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000528/WC500036658.pdf
  55. 55.
    EMA European Public Assessment Report (EPAR): Elelyso (Recombinant Taliglucerase Alfa) (2012); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002250/WC500135112.pdf
  56. 56.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – Elelyso (Recombiant Taliglucersase Alfa) – Approval Date(s) and History, Letters, Labels, Reviews – Review – Other Action Letters (February 2011); www.accessdata.fda.gov/drugsatfda_docs/nda/2012/022458Orig1s000OtherActionLtrs.pdf
  57. 57.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Flubloc (Recombinant Influenza Vaccine Antigen) – Package Insert (2013); www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM336020.pdf
  58. 58.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Flubloc (Recombinant Influenza Vaccine Antigen) – Summary Basis for Regulatory Action (January 2013); wayback.archive-it.org/7993/20170723030121/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM338898.pdf
  59. 59.
    EMA European Public Assessment Report (EPAR): Cervarix (Human Papillomavirus Vaccine) (2007); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000721/WC500024636.pdf
  60. 60.
    Ma, H., Galvin, T. A., et.al., Identification of a Novel Rhabdovirus in Spodoptera Frugiperda Cell Lines, J. Virol. (2014) 88(12): 6576–6585CrossRefGoogle Scholar
  61. 61.
    Parenteral Drug Association (PDA): Technical Report No. 71 – Emerging Methods for Virus Detection (2015); PDA website, www.PDA.org
  62. 62.
    EMA European Public Assessment Report (EPAR): Glybera (Alipogene Tiparvovec) (2012); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002145/WC500135476.pdf
  63. 63.
    EMA European Public Assessment Report (EPAR): Imlygic (Talimogene Laherparepvec) (2015); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002771/WC500201082.pdf
  64. 64.
    EMA European Public Assessment Report (EPAR): Imvanex (Modified Vaccinia Ankara) (2013); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002596/WC500147898.pdf
  65. 65.
    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
  66. 66.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Provenge (Sipuleucel) – Package Insert (2010); www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM210031.pdf
  67. 67.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Laviv (Azficel-T) – Package Insert (2011); www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM260489.pdf
  68. 68.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Gintuit (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) – Package Insert (2012); www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM295525.pdf
  69. 69.
    EMA Find Medicine – Human Medicine: 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) – Product Information (June 2016); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002801/WC500212514.pdf
  70. 70.
    EMA Guideline on the Quality of Biological Active Substances Produced by Stable Transgene Expression in Higher Plants, EMEA/CHMP/BWP/48316/2006 (July 2008); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003154.pdf
  71. 71.
    Parshley, L., ZMapp: The Experimental Ebola Treatment Explained – How Tobacco May Help Defeat One of the World’s Deadliest Viruses (August 8, 2014); Popular Science Magazine, www.popsci.com/article/science/zmapp-experimental-ebola-treatment-explained
  72. 72.
    EMA European Public Assessment Report (EPAR): ATryn (Recombinant Antithrombin Alfa) (January 2007); www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000587/WC500028257.pdf
  73. 73.
    Genzyme Press Releases in 2009; Sanofi Genzyme website, www.sanofigenzyme.com
  74. 74.
    Rosenberg, A.S., Cherney, B., et.al., Risk Mitigation Strategies for Viral Contamination of Biotechnology Products: Considerations of Best Practices; PDA J Pharm Sci Technol (2011), 65: 563–567CrossRefGoogle Scholar
  75. 75.
    PDA Workshop. Mycoplasma Contamination by Plant Peptones. Mycoplasma Contamination: Challenges and. Opportunities for the Biotechnology Industry (2005); www.PDA.org/bookstore
  76. 76.
    PDA Technical Report No. 75 – Consensus Method for Rating 0.1 μm Mycoplasma Retention Filters (2016); www.PDA.org/bookstore
  77. 77.
    PDA Technical Report No. 50 – Alternative Methods For Mycoplasma Testing (2010); www.PDA.org/bookstore
  78. 78.
    Roche Diagnostics Technical Report: Mycoplasma Testing of Biopharmaceuticals: Current Regulations, Challenges and Trends (2018); www.custombiotech.roche.com/content/dam/internet/dia/custombiotech/custombiotech_com/en_GB/pdf/CustomBiotech_Mycoplasma_testing_of_Biopharmaceuticals_Booklet.pdf
  79. 79.
    Duguid, J., Lessons Learned from Validation of a Real-Time PCR Mycoplasma Test for Autologous Cell Therapy Products; American Pharm Review (2013), Sept/Oct: 96–102Google Scholar
  80. 80.
    Wang, J., Johnson, S., et al., Mycoplasma Clearance and Risk Analysis in a Model Process; PDA J Pharm Sci Technol (2017) 71: 99–114CrossRefGoogle Scholar
  81. 81.
    FDA Guidances (Drugs): Questions and Answers on Current Good Manufacturing Practices, Good Guidance Practices, Level 2 Guidance – Production and Process Controls; FDA website, www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124782.htm#3
  82. 82.
    Centers for Disease Control and Prevention (CDC) Antibiotic/Antimicrobial Resistance: Biggest Threats – Emerging Drug Resistance; CDC website, www.cdc.gov/drugresistance/emerging.html
  83. 83.
    FDA CBER History: The Road to Biotech Revolution – Highlights of 100 Years of Biologics Regulation (2006); www.fda.gov/downloads/AboutFDA/WhatWeDo/History/ProductRegulation/UCM593490.pdf
  84. 84.
    FDA Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letter – ID Biomedical (June 12, 2014); www.fda.gov/ICECI/EnforcementActions/WarningLetters/2014/ucm401719.html
  85. 85.
    FDA Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letter – Alexion Pharmaceuticals (March 22, 2013); www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm347063.htm
  86. 86.
    FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice (September 2004); www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070342.pdf
  87. 87.
    European Commission (EC) Volume 4 GMP Human & Veterinary: Annex 1 – Manufacture of Sterile Medicinal Products (Revision Published for Comment) (December 2017); ec.europa.eu/health/sites/health/files/files/gmp/2017_12_pc_annex1_consultation_document.pdf
  88. 88.
    FDA Inspections, Compliance, Enforcement, and Criminal Investigations: Warning Letter – Celltrion Inc. (January 26, 2018); www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm594395.htm
  89. 89.
    Gray, J.C., Staerk, A., et al., Introduction of a Rapid Microbiological Method as an Alternative to the Pharmacopeial Method for the Sterility Test; American Pharm. Rev., 13 (September–October 2010) 88–94Google Scholar
  90. 90.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – Erelzi (Recombinant Etanercept-szzs Fusion Protein, Biosimilar) – Approval Date(s) and History, Letters, Labels, Reviews – Review – Chemistry Reviews (August 2016); www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761042Orig1s000ChemR.pdf
  91. 91.
    ICH Q5D: Derivation and Characterization of Cell Substrates Used For Production of Biotechnological/Biological Products (July 1997); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5D/Step4/Q5D_Guideline.pdf
  92. 92.
    FDA Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products For Human Use (February 1997); www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/OtherRecommendationsforManufacturers/UCM153182.pdf
  93. 93.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – Eylea (Aflibercept): Approval History, Letters, Reviews and Related Documents – Administrative and Correspondence Documents – Pre-BLA Meeting (September 27, 2010); www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125387Orig1s000Admincorres.pdf
  94. 94.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – Adcetris (Brentuximab Vedotin): Approval History, Letters, Reviews and Related Documents – Administrative and Correspondence Documents – Pre-BLA Meeting (December 07, 2010); www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125388Orig1s000AdminCorres.pdf
  95. 95.
    FDA Drugs – Search Drugs@FDA: FDA Approved Drug Products – Blincyto (Blinatumomab): Approval History, Letters, Reviews and Related Documents – Administrative and Correspondence Documents – Pre-BLA Meeting (April 09, 2014); www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125557Orig1s000AdminCorres.pdf
  96. 96.
    FDA Vaccines, Blood & Biologics: Licensed Biologic Products with Supporting Documents – Kymriah (Tisagenlecleucel) – Package Insert (2017); www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM573941.pdf
  97. 97.
    European Commission (EC) Volume 4 Good Manufacturing Practice: Guidelines to Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products (Novembber 2017); ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf
  98. 98.
    EMA Press Release: European Medicines Agency Confirms Positive Benefit-Risk Balance of MabThera – Batches Produced at the Vacaville Manufacturing Site Do Not Pose Risk to Public Health, (May 2012); www.ema.europa.eu/docs/en_GB/document_library/Press_release/2012/05/WC500127776.pdf
  99. 99.
    Chen, J., Bergevin, J., et. al, Case Study: A Novel Bacterial Contamination in Cell Culture Production – Leptospira Licerasiae; PDA website, PDA J Pharm Sci and Tech. (2012), 66: 580–591CrossRefGoogle Scholar
  100. 100.
    FDA Drugs – Guidance, Compliance & Regulatory Information: Questions and Answers on Current Good Manufacturing Practices—Production and Process Controls – 14. Can Leptospira Species Penetrate Sterilizing-grade Filters?; FDA website, www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124782.htm#14.

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

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

Personalised recommendations