Dr. Archie Lovatt
Scientific Director for Biosafety, SGS
With the world preparing to begin mass COVID-19 vaccination programs, how do scientists ensure vaccines remain safe?
Vaccine safety is the primary concern of all regulatory agencies. To ensure only safe and sterile products reach patients, they impose stringent limits on the amounts of microbial contaminates and impurities that can be present during manufacturing.
Scientists develop and implement a detailed quality control (QC) testing strategy at the earliest stage of a vaccine’s development – when the first material for use in human clinical trials is produced – to ensure these limits are met. The QC testing strategy is developed for the vaccine.
Vaccines are often weakened or inactivated whole viral vaccines, or viral vectors (e.g. defective adenoviruses) made in cell cultures expressing the immunogenic protein (e.g. a purified spike protein of COVID-19 coronavirus). They may also be a purified immunogenic protein made in cell bioreactors. (Table 1A and 1B).
More recently, newer vaccines have emerged in the form of mRNA molecules encoding the immunogen once inside the patient’s cells (for example, the Pfizer and Moderna COVID-19 vaccines).
Testing at every stage
Appropriate testing methods are used to check starting materials (cell banks, viral seed banks and media), intermediates (bulk harvests), and sterile batches of the purified vaccine clinical product. It is also critical to authenticate the vaccine’s identity to avoid patients being injected with the wrong product. This is done using nucleic acid based DNA sequence technology.
The vaccine is also screened for purity at every stage of the manufacturing process to ensure it is free from contaminants, such as unwanted bacteria or fungi, using standard sterility assays, and contaminating viruses.
Using a broad spectrum approach
Due to their diverse nature and growth requirements, contaminating viruses are much more difficult to detect than bacteria and fungi. High magnification transmission electron microscopy studies, cell infectivity, and molecular biology methods like PCR and DNA sequencing are used to detect unknown viruses at each production stage.
It is also important to demonstrate that at the purification stage, any residual materials, such as cellular DNA and proteins or other ingredients, have been removed to acceptable limits. Residual impurities are detected and quantified using techniques like PCR and ELISA. Without consistency in vaccine purity, regulators will question clinical trial data.
Once the vaccine is approved for general use in humans, the QC testing strategy is employed for every batch to ensure safety standards are maintained.