Biological standards: problems in large-scale production

A biological standard usually consists of a batch of perhaps several thousand ampoules. In defining a batch of ampoules to be a standard, we are in essence making a number of fundamental claims: (1) That in terms of content, (mass and potency) each individual ampoule is identical to every other amoule in the batch. (2) That in the course of preparation of the standard, the contents of each ampoule have been treated in exactly the same way and held for the same length of time under the same conditions, (i.e. all the ampoules of the standard have been treated as one single batch, each stage of processing being carried out under constant conditions in one complete working session, however long). (3) That the stability or instability of the biological activity of the contents of each ampoule of the batch is identical to every other ampoule (i.e. that moisture, oxygen, light, raised temperature--all factors which cause deterioration of biological activity--have been exculuded to the same degree in each and every ampoule in the batch, so that each ampoule of the standard is equally stable or unstable). It is quite a difficult task to meet these criteria even in a small number of ampoules at the bench. It becomes a very demanding exercise to achieve the same results in 4,000 ampoules--the normal batch size at NIBSC. Details of the methods used at NIBSC for the production of large batches of ampoules of biological standards have already been published (Campbell, 1974). The author of the papers will take the opportunity to develop various aspects of the published detail.