FDA Issues Guidance for Manufacturing Cell-Based Viral Vaccines

The US Food and Drug Administration recently published a final guidance for the characterization and qualification of cell substrates, viral seeds, and other biological materials used to manufacture viral vaccines for human use. Manufacturers use cell cultures to produce vaccines against diseases such as measles, mumps, and polio. FDA’s new guidance advises manufacturers about how to test cell substrates and choose appropriate materials for producing their vaccines.

Cell-based manufacturing allows manufacturers to freeze, store, and thaw cells as needed to produce more vaccine. This technique could be the basis of a flexible approach to production that provides surge capacity during emergencies.

FDA’s new guidance could promote the development of reliable alternate methods of producing influenza vaccines, which are currently produced in chicken eggs using a technique developed more than 50 years ago. Flexible approaches to production are important at a time when demand for seasonal influenza is increasing and new infectious diseases are emerging.

The guidance document is limited to cell substrates of human or animal-including insect-origin and does not describe the characterization of unicellular organisms such as bacteria or yeast. In one of the first sections of the guidance, FDA describes the properties that are relevant to cell-substrate selection such as growth and expression characteristics. The agency also explains various cell-banking strategies and how they affect cell-substrate characterization and qualification methods. In addition, FDA lists tests that manufacturers can perform at various stages of production.

A separate section of the guidance describes test methods for adventitious agents. FDA explains procedures for in vivo tests, in vitro tests for viruses, and in vitro tests for nonviral agents. The guidance also describes how to perform cell-property tests such as tests for tumorigenicity, oncogenicity, and genetic stability.

The new guidance, Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications, finalizes the draft guidance titled Characterization and Qualification of Cell Substrates and Other Biological Starting Materials Used in the Production of Viral Vaccines for the Prevention and Treatment of Infectious Diseases, which was published in September 2006.