Abstract
It is shown that in the eyes of both the FDA and the EMA, biologics are definitely different from chemical drugs. This is not a perception, but a reality, and it is reflected by the statements on their websites and in the wording of the regulatory guidances that they issue. Also, as is shown in this chapter, the three major differences between biologics and chemical drugs are discussed: (1) use of living source materials to produce the biologic, (2) increased complexity of biologic manufacturing processes, and (3) increased complexity of the biologic molecules themselves. Finally, in this chapter, an explanation is presented of why biosimilar biological products are best viewed as similar biologics and not as true generics.
As soon as you go into any biological process in any real detail, you discover it’s open-ended in terms of what needs to be found out about it.
Joshua Lederberg, American molecular biologist,
Nobel Prize winner, 1925–2008
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FDA 101: Biological Products; FDA website, www.fda.gov/ForConsumers/ConsumerUpdates/ucm048341.htm
FDA Frequently Asked Questions About Therapeutic Biological Products; CDER website, www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm113522.htm
FDA Guidance for FDA Reviewers and Sponsors – Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) (April 2008); www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/ucm078694.pdf
FDA Guidance for FDA Reviewers and Sponsors – Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) (April 2008); www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Xenotransplantation/ucm092705.pdf
EU EudraLex The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, Annex 2 Manufacture of Biological Medicinal Substances and Products for Human Use (June 2012); ec.europa.eu/health/files/eudralex/vol-4/vol4-an2__2012-06_en.pdf
EMA Guideline on Similar Biological Medicinal Products, CHMP/437/04 (October 2005); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003517.pdf
ICH Q6A Specifications: Test Procedures and Acceptance Criteria For New Drug Substances and New Drug Products: Chemical Substances (October 1999); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6A/Step4/Q6Astep4.pdf
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
ICH Q1A(R2) Stability Testing of New Drug Substances and New Drug Products (February 2003); www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_R2__Guideline.pdf
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
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
FDA Biotechnology Inspection Guide (November 1991); FDA website, www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074181.htm
FDA BLA Market Approval of Rituxan (Rituximab): Approval History, Letters, Reviews and Related Documents – Product Review (November 19, 1997) – CDER, Drugs@FDA, website ; www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm107743.pdf
Kozlowski, S. and Swann, P., Current and Future Issues in the Manufacturing and Development of Monoclonal Antibodies; Advanced Drug Delivery Reviews, Volume58,Issues5–6, 7 August 2006, Pages 707–722
EMA Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins, EMEA/CHMP/BMWP/14327/2006 (December 2007); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003946.pdf
United States Pharmacopoeia (USP), General Tests and Assays: <197> Spectrophotometric Identification Tests; USP website, www.USP.org
United States Pharmacopoeia (USP), General Information: <1047> Biotechnology-Derived Articles – Tests, Peptide Mapping; USP website, www.USP.org
United States Pharmacopoeia (USP), Official Monographs: Insulin Human; USP website, www.USP.org
FDA Information For Consumers (Drugs): Understanding Generic Drugs; CDER website, www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingGenericDrugs/default.htm
EMA Procedural Advice For Users of the Centralised Procedure For Generic/Hybrid Applications (2011); www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004018.pdf
EMA Guideline on Similar Biological Medicinal Products, CHMP/437/04 (October 2005); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003517.pdf
Health Canada Questions and Answers to Accompany the Final Guidance For Sponsors: Information and Submission Requirements For Subsequent Entry Biologics (SEBs); www.hc-sc.gc.ca/dhp-mps/brgtherap/applic-demande/guides/seb-pbu/01-2010-seb-pbu-qa-qr-eng.php
World Health Organization Expert Committee on Biological Standardization: Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs) (2009); www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf
EMA Guideline on Similar Biological Medicinal Products, CHMP/437/04 (October 2005); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003517.pdf
EMA Guideline (Draft) on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues (Revision 1), EMA/CHMP/BWP/247713/2012 (May 2012); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/05/WC500127960.pdf
EMA Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-clinical and Clinical Issues, EMEA/CHMP/BMPW/42832/2005 (February 2006) ; www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003920.pdf
Health Canada Fact Sheet: Subsequent Entry Biologics in Canada (September 2009); www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/brgtherap/fs-fi_seb-pbu_07_2006-eng.pdf
World Health Organization Expert Committee on Biological Standardization: Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs) (2009); www.who.int/biologicals/areas/biological_therapeutics/BIOTHERAPEUTICS_FOR_WEB_22APRIL2010.pdf
FDA Assessing the Impact of a Safe and Equitable Biosimilar Policy in the United States, Statement of Janet Woodcock, M.D. Deputy Commissioner, Chief Medical Officer, Food and Drug Administration before the Subcommittee on Health, House Committee on Energy and Commerce (May 2, 2007); FDA website, www.fda.gov/NewsEvents/Testimony/ucm154017.htm
FDA Guidance For Industry (Draft) Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009 (February 2012); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273001.pdf
FDA Guidance For Industry (Draft) Scientific Considerations in Demonstrating Biosimilarity to a Reference Product (February 2012); www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf
EMA Concept Paper on the Revision of the Guideline on Similar Biological Medicinal Product, EMA/CHMP/BMWP/572643/2011 (November 2011); www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/11/WC500117987.pdf
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Geigert, J. (2013). Biologics Are Not Chemical Drugs. In: The Challenge of CMC Regulatory Compliance for Biopharmaceuticals and Other Biologics. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6916-2_2
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DOI: https://doi.org/10.1007/978-1-4614-6916-2_2
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