Bioassay (or biological method) is an important part for quality assessment in the production and marketing of biological products and other drugs. Validation of bioassay is an important scientific approach to ensure the accuracy and robustness of the test results and then ensure the reliability of the quality of biological products. Validation is one of the critical control points of the quality assurance system, and also the key audit content of various certifications and accreditations such as GMP and laboratory certification.

    Bioassay which could be used to assess product quality was formed in the early 20th century. Throughout the 20th century, scientists from the fields of biology and statistics mainly focused on the research of application of this method, which was known as “bioactivity control method” in China, because of its many influencing factors, complicated operation and great variability of results.Since 2010, global methodological researchers in the pharmaceutical field had re-examined the validation contents of bioassay and physio-chemical methods according to the development and penetration of analytical quality by design (AQbD), life cycle, risk assessment and Six Sigma, and they transferred their research focus from application to the front end, such as the design, development and validation of bioassay. Thus, it could be truly started that the systematic methodology research stage of bioassay. For details, please refer to the “Overview of methodology research on bioassay” in this column.

    10 papers contained in this column were the research summaries of more than 6 years, funded by the National Major New Drug Creation Project, Pharmacopoeia Projects, and the Quality Safety and Capability Building Project from NIFDC. In 2019, a phased summary column was published about part methodological research contents of physical and chemical methodsin the February issue of this magazine. The contents published in this issue are systematic research and innovative application based on extensive reference to the international research of bioassay.In this column, the process of historical development, the status quo of domestic and foreign regulation and guidelines and the latest research progress of bioassays are doing textual researched in the paper “Overview of methodology research on bioassay”. The definition and systematic classification of bioassays with the help of terminology theory was explored, and several expressions were discriminated about the name of bioassay in China, so as to help readers scientifically understand the essence of biological activity testing methods from a global perspective in the paper “Definition and taxonomy of biological method”. The most commonly used and easy confusing terms in bioassay studies were explained and compared in the paper “Analysis of key terms in bioassay”. Knowledges, which urgent needed for the establishment and evaluation of dose-effect model in the validation of bioassays, was focused on in the paper “Discussion on how to set up the dose-response model of bioassay”. The shortcomings in presentation of the values of biological potency were analyzed, and the integrity of presentation content in specification and daily report (including information about method suitability, the acceptance criterion and the significant figure of reportable value) and related calculation theory were systematically expound, in the two papers “Discussion on the scientific and standardized expression for reportable value of biological potency” and “Discussion on key points for setting up of the acceptance criteria of biological potency”. The experiment design to obtain accurate and reliable method performance parameters from the perspective of risk analysis and statistics was expounded and some common experimental design and thinking mode for design of method validation were provided in the paper “Discussion on the experiment design of bioassay validation”. The capability indexes which could describe the method capability were systematically summarized, including tolerance intervals and prediction interval of reported value, method capability index and method misjudgment rate, in the paper “Discussion on the evaluation indexes and criteria of assay for satisfying its intended use”. Some valuable application indexes of method that can be derived from the data set after method validated were mainly explored and summarized, including the format variability of method, the difference threshold of report value, the standard deviation for proficiency testing and the risk analysis of the key factors influencing the method, in the paper “Discussion on the application of method validation data set”. Finally, software named BMV 1.0 was introduced in the paper “Design and function of statistical software for validation of biological methods”, which was independently built by our laboratory to help experimenters solve the statistical analysis difficulties and get the indexes of method in the bioassay validation.

    It is hoped that the publication of this column could provide systematic and comprehensive theoretical basis and statistical analysis support for peoples who worked in drug regulatory authorities, quality assessment laboratories and production enterprises in the evaluation of bioassay.