Vaccine Pre-clinical Toxicology Testing

Additional flowchart detail

1. Establish the manufacturing & controls, filling process (may not be final at this stage) - controls should include in-process, bulk testing, and final container lot release
2. Establish mixing parameters to ensure homogeneity, i.e., that the dosing solution contents are uniform throughout the vial and from vial to vial
3. Establish assays for lot release testing (may not be validated at this stage)
4. Establish method for determining vaccine potency (may not be final or validated at this stage)
5. Define test (e.g., bioburden), method (e.g., 25 USP <61>), and criteria (may not be final at this stage; e.g., <100 CFU and no objectionable organisms) for each bulk and filled lot of manufactured vaccine, Certificate of Analysis (COA)
6. Establish stability under storage & conditions of use during shipping & dose administration (according to a stability plan)

http://www.fda.gov/cber/gdlns/plasmid.pdf page 22

http://www.fda.gov/cber/gdlns/plasmid.pdf page 24 for DNA vaccines and/or http://www.fda.gov/cber/gdlns/reprotox.pdf

http://www.fda.gov/cber/gdlns/plasmid.pdf page 25

Other product specific safety assessments may include, but are not limited to: neurovirulence, attenuation, distribution within airways of delivery by a nasal delivery device, particle size distribution delivered by a delivery device, toxicology of excipients, including adjuvants (including cytokines), allergenicity, formation of neo-antigens (unwanted immunogenicity), autoimmunity, etc. The necessity for these specialized safety assessments is based on the vaccine modality or may be product-specific, thus, it may be determined on a case-by-case basis. Guidance should be sought from CBER, preferably in the format of a pre-IND meeting.