Design and analysis of accelerated degradation tests for the stability of biological standards III. Principles of design.

The principles of designing an accelerated degradation test for a biological standard are considered, with special emphasis on ensuring accuracy and precision of the predicted low temperature degradation rate. A three-stage design is proposed which initially monitors samples at the highest of the elevated temperatures, but which switches attention progressively to the lower temperatures as degradation begins to be detected. The advantages of this design over one where testing is carried out after a predetermined period are that it is (i) more efficient, (ii) more reliable and (iii) better suited to test the assumptions which underly the analysis of the results. Consideration is also given to additional checks which can be made on the stability of biological standards and to methods of monitoring long-term stability after the standard has been set up.