The Seed Lot System

THE SEED LOT SYSTEM

The starting point for the production of all microbial vaccines is the isolation of the appropriate infectious agent. Such isolates have usually been derived from human infections and in some cases have yielded strains suitable for vaccine production very readily; in other instances a great deal of manipulation and selection in the laboratory have been needed before a suitable strain has been obtained. For example, bacterial strains may need to be selected for high toxin yield or production of abundant capsular polysaccharide; viral strains may need to be selected for stable attenuation or good growth in cell cultures.

Once a suitable strain is available, the practice is to grow, often from a single viable unit, a substantial volume of culture which is distributed in small amounts in a large number of ampoules and then stored at −70°C or below, or freeze-dried. This is the original seed lot. From this seed lot, one or more ampoules are used to generate the working seed from which a limited number of batches of vaccine are generated. These are first examined exhaustively in laboratory and animal tests and then, if found to be satisfactory, tested for safety and efficacy in clinical trials. Satisfactory results in the clinical trials validate the seed lot as the material from which batches of vaccine for routine use can subsequently be produced.

It is important that the full history of the seed is known, including the nature of the culture media used to propagate the strain since isolation. If at all possible, media prepared from animal products should be avoided. If this is not practicable, media components must be from sources certified free of transmissible spongiform encephalopathy (TSE) agents.