Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Manufacturing of Cervarix


Published on

Published in: Health & Medicine
  • Be the first to comment

Manufacturing of Cervarix

  1. 1. Group 6
  2. 2. • Cervical Cancer & HPV• Cervarix (HPV vaccine)• The Manufacturing process• Quality Control• Conclusion
  3. 3. • Cervical cancer is a malignant neoplasm of the cervix uteri or cervical area.• Worldwide, it is the twelfth most common and fifth most deadly cancer in women.• It affects about 16 per 100,000 per year and kills about 9 per 100,000 per year globally.
  4. 4. • Cervarix is a preventive vaccine against certain types of cancer causing human papillomavirus.• Manufactured at GlaxoSmithKline Biologicals S.A. in Belgium.• Aims to prevent infection from HPV types 16 & 18 that cause about 70% of cervical cancer cases.• Developed, in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland Australia and the US National Cancer Institute
  5. 5. • Approved for use in females 10-25 years of age.• Consists of 3 doses of 0.5 mL each, by intramuscular injection at 0, 1 and 6 months.• The vaccine is available in 0.5 mL single dose vials and prefilled TIP-LOK syringes• Cervarix has shown to be 92% effective and effective for more than 4 years.• Shelf life: 3 years.
  6. 6. Cervical cancer vaccine Annual Sales World Wide ($m)salesProduct Company 2008 2010 2012 2014Gardasil Sanofi-Pasteur 865 1,222 1,686 1,984 MSDGardasil Merck & Co 1,403 1,227 1,399 1,372Cervarix GlaxoSmithKlin 231 797 1,246 1,353 eTotal HPV vaccine market 2,499 3,246 4,331 4,709 Adapted from GSK: 2010 Annual Report, Sanofi 2009 Annual Report
  7. 7. 2000 1800HPV sales ($m) 1600 1400 1200 1000 800 600 400 200 0 2014 2012 2010 2008
  8. 8. • Cervarix, HPV-16/18 L1 AS04 vaccine contains recombinant C-terminally truncated major capsid L1 proteins of HPV types 16 and 18 as active ingredients• The first vaccines for humans from Baculovirus Expression System
  9. 9. • The L1 proteins of HPV-16 and HPV-18 are separately produced• Usage of a:  recombinant Baculovirus expression system  insect cell line Hi-5 Rix4446 derived from Trichoplusia ni
  10. 10. • High levels of heterologous gene expression• Grows well in suspension cultures, easy for large- scale production• Safe (restricted to infection of invertebrate species)• Cheaper as Hi-5 Rix4446 can be cultured in serum free medium
  11. 11. Amplification of Seed Recombinant Formulation, filling and packaging Baculovirus Extraction of Recombinant Combination of HPV 16 and 18 L1 Baculovirus inocula proteins Infection of Trichoplusia ni Hi-5 Sterile filtration of L1 VLPproduction cell lines in fermenter Purification by L1 proteins are extracted by chromatography, nanometric methods of osmotic shock filtration and ultrafiltration
  12. 12. • The cell lysate may be subjected to a microfiltration and ultra-filtration process• Cation- exchange chromatogrophy• Hydroxyapatite Chromatography - hydroxyapatite as the column medium - elution with a buffer solution containing phosphate anion - removes a large amount of contaminants from a partially purified cellular lysate - Removes contaminating biomolecules, including DNA, lipids and proteins are removed from the lysate.
  13. 13. • The L1 proteins• AS04 adjuvant system composed of- aluminium hydroxide- 3-O-desacyl-4.- monophosphoryl lipid A (MPL)• The MPL immunostimulant- a detoxified derivative of the lipopolysaccharide ofthe gram negative bacterium Salmonella minnesotaR595 strain.
  14. 14. CELL SEED AND BANKING• The MCB, WCB, MS and WS and End of Production Cells (EPC) are tested for identity, purity and safety• The Assays are: – Tumourogenic Potential – Adventitious Agents – Genetic Stability – Specific Viral Contaminants
  15. 15. PROCESS CONTROL & VALIDATION• The 3 unit-steps of the drug substance production process are tested for consistency: – The recombinant HPV-16/18 baculovirus inoculum production process – The L1 single harvest production and L1 extraction – The L1 antigen purification process. MANUFACTURING PROCESS DEVELOPMENT• the final process purified bulks, are assessed by subjecting each type of materials to a series of physico-chemical analyses and immunogenic property tests.
  16. 16. Physico-Chemical Analyses Immunogenic Properties• SDS-PAGE • Antigenic activity• Western blotting• Capillary electrophoresis • Binding to polyclonal sera• Mass spectrometry • Immune response elicited in• Amino acid analysis mice• Peptide mapping• N-and C-terminal analysis• Infra-Red and circular dichromism spectroscopy• Size exclusion chromatography• Electron microscopy• Disc centrifugation size analysis
  17. 17. • Cervarix is a vaccine that prevents infection from HPV types 16 and 18• Market• Manufacured and purified from expression of L1 proteins in the Hi-5 Rix4446 insect cells