Kerstin Dolph, Horst Ruppach, and Katee Fry
Vaccine Safety from Development to Distribution
From cell banking to stability testing, how biologics keeps vaccine manufacturing safe
Vaccine development typically takes years, even decades. How then could companies deliver COVID-19 vaccines in a matter of months? Can we trust the process? These two questions have been dominating the airwaves ever since the first three candidates in the pipeline were authorized by regulators, a mere 11 months after SARS-CoV-2 emerged in China. We hope Eureka’s five-part series, The Vaccine Journey, on how vaccines are developed—from discovery through manufacturing—helps answer some of these questions and reassures readers that vaccines are generally very safe. Biologics experts Kerstin Dolph, Horst Ruppach, and Katee Fry explain how biologics testing keeps vaccine manufacturing safe.
In 1955 hundreds of thousands of children were injected with a defective polio vaccine. The Cutter incident, as it came to be known, occurred during intense public demand for immediate distribution of a lifesaving vaccine that had just been invented. Cutter Laboratories, a vaccine manufacturer, had failed to properly inactivate their viruses, leading to vaccines containing live instead of dead polio viruses. Public outcry was swift, and distrust of the new polio vaccine began to take root.
If these fears sound familiar, rest assured: as a direct result of the Cutter incident, the US and many other countries tightened safety protocols around vaccines, making them now one of the most closely regulated and tested medical products.
The Cutter incident was a failure at the manufacturing level. Our work in biologics testing helps to ensure that incidents like this cannot happen again, even before clinical trials. Any vaccine that is given to human subjects, including all varieties of COVID vaccines, must undergo vigorous testing by the sponsor or by a contract services provider like Charles River to make sure there are no errors introduced during manufacturing. After all, the best designed vaccines in the world are useless if they are made incorrectly.
Vaccine Safety Testing
Before a vaccine begins human trials, it is subjected to a barrage of tests to ensure the product’s safety and efficacy. The kinds of safety tests required and performed depend on the vaccine. This pre-clinical stage also helps identify potential side effects from a vaccine that was not detected in earlier trials, and which may occur during the larger scale manufacturing of a vaccine.
For clinical trials, additional safety requirements must be implemented to ensure safety. Cell banks used to produce different types of vaccines must be fully characterized and analyzed for potential pathogens (viruses, bacteria). The product itself is analyzed for process or product related impurities. If applicable, the capacity of the purification process to remove or inactivate potential viral contaminants is determined. Any aspect of mass production that differs from the lab-created vaccines needs to be assessed for safety.
Vaccine Stability Testing
Once a vaccine is deemed safe, we must also determine how stable it is. This includes how long the product can last and how it should be stored, including whether the product has any sensitivities to its container/closure, temperatures, moisture, orientation, and/or exposure to light.
The cold-storage requirements for some of the COVID-19 vaccines has been covered thoroughly in the news, and this information was gathered through stability testing. While those who developed the vaccine knew from the beginning that their product would need special storage, the exact temperatures, specific approved types of storage containers, and timing requirements for defrosting were all determined at the stability testing stage. The storage requirements for the vaccine must be those conditions under which the particular product was tested, thus seemingly similar products can have different storage conditions as the manufacturers conducted their specific stability testing under different conditions. As further studies are conducted, changes can be made to the storage conditions.
Vaccine Release Testing
Biologics testing is not always a straight line. Some of these tests are run simultaneously, some are tested multiple times at different intervals and with different conditions, and the cycle continues until this final stage: release testing. At Charles River, this stage requires the finished product to undergo a final set of critical validated tests to confirm its safety and efficacy for its intended use.
We are proud to offer a package that covers everything needed for release testing. There are few biologics testing providers with the full portfolio of services, and as a result we often feel great personal responsibility to the vaccines in our care. The biologics team is the last in a series of players between vaccine discovery and final manufacturing, and we are proud to play an integral role in ensuring patient safety.
Kerstin Dolph, Corporate Vice President, Global Biologics Testing Solutions, joined Charles River in 2001 as part of our Research Models and Services (RMS) Finance Department in Germany. In her current role Mrs. Dolph is responsible for leading the Company’s Biologics business, as well as managing its growth opportunities and the expansion of the business.
Katee Fry, Senior Marketing Manager, has 15 years of industry experience, including over two years with Charles River's biologics division.
Dr. Horst Ruppach has 25 years of experience in the field of virology. He is currently responsible for the business development of Charles River’s viral clearance and virology service worldwide.