[SaneVax: This document is for the serious researcher. Whether you are a vaccine safety advocate, medical professional or scientist, you will want to look at the concerns expressed during the last Vaccines and Related Products Advisory Committee (VRBPAC) meeting on 9 Sept 2012. The FDA briefing document table of contents is printed below for your convenience. Access the entire document here. Please, take a few minutes to at least scan through this important information. The time for relying on pharmaceutical manufacturers to provide the truth is long past.]
Table of Contents
Cell Lines Derived from Human Tumors for Vaccine Manufacture
1. Introduction .. 4
2. Background . ..4
2.1 History of Cell Substrates for Viral Vaccine Manufacture in the U.S.: Primary,
Diploid, and Tumorigenic Cells . 5
2.2 Cell Substrates Derived from Human Tumors Proposed for Manufacture of
Viral vaccines 6
3. Considerations Regarding the Use of Tumor-derived Cell Lines .. 8
3.1 Mechanism of Tumorigenesis and Considerations for Characterization of Cell
Substrates . .. 8
3.1.1 Oncogenic Viruses .. . .9
3.1.2 Somatic Mutations .. .9
3.1.3 Epigenetic Changes . .. 10
3.2 Metastatic Potential . 11
4. Recommendations for Testing of Cell Substrates and Vaccines .12
4.1 Adventitious Agents . . .12
4.1.1 Background 12
4.1.2 Current Recommendations for Characterization and Testing of Cell Substrates . . . ..13
4.1.3 Emerging Technologies for Viral Detection .. . .. . 14
4.1.4 Viral Clearance by the Manufacturing Process.. . .. . 15
4.2 Residual Cell-substrate DNA . .15
4.2.1 Background: DNA Oncogenicity, DNA Infectivity, and DNA Integration ..15
4.2.2 Current Recommendations for Control of Whole Cells and Host-cell DNA Content in Vaccines . . 17
5. Summary . .. 18
Appendix 1: Prior VRBPAC Discussions and other Meetings on Cell Substrates 19
Appendix 2: Cell Substrate Recommended Testing from Guidance for Industry:
Characterization and Qualification of Cell Substrates and Other Biological Materials Used in
the Production of Viral Vaccines for Infectious Disease Indications .. . 22
Appendix 3: Summary of Selected Emerging Technologies for Virus Detection . 24
Appendix 4: WHO Deliberations: Issues Associated with the Presence of Residual
Cell-substrate DNA in Vaccines .. . 25
References .. ..26
Attachments:
1. Guidance for Industry (February 2010): Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications
2. Review Article (Anal. Chem. 83, 4327-4341; May 25, 2011): Landscape of Next Generation Sequencing Technologies by Thomas P. Niedringhaus, Denitsa Milanova, Matthew B. Kerby, Michael P. Snyder, and Annelise E. Barron