China's biologic drug research and development is on a fast track lane. The rising cost of new drug development has not improved the success rate of drug launch, and a shift in the model of drug development is urgently needed. In order to improve the success rate, a biomarker strategy of the new drug development model has been proposed and is generally accepted. This paper reviews the research and development of new translational medicine drugs with biomarkers as the core, the application of biomarkers in the clinical study of biological drugs, biomarker biological analysis strategies, and the opportunities and challenges of biomarkers in the clinical study of biological drugs. By comparing international standards, seeking China's advantages and seeking opportunities from the research and development model of translational medicine based on biomarkers, China can make innovative drugs with global influence in the near term.

AIM To investigate the tissue distribution of exendin-4 after administration in healthy rats. METHODS Exendin-4 was radioiodinated by the Iodo-GenTMmethod. Tissue distribution of [125I]exendin-4 was investigated after sc administration of [125I]exendin-4 at 3 μg·kg-1 in rats. Both total radioactivity and trichloroacetic acid (TCA) precipitated radioactivity were used to calculate the levels of [125I]exendin-4 in rats plasma and tissue samples after sc administration. RESULTS The tissue distribution of [125I]exendin-4 after sc injection showed substantial disposition in kidneys, lungs, bladder and pancreas. The rank order of normalized tissue distribution was kidneys＞lungs＞bladder＞pancreas＞intestine＞plasma＞adrenals>jejunum＞lymph＞liver＞spleen＞heart＞marrow＞thymus＞testicles＞brain＞muscle＞adipose. CONCLUSION [125I]Exendin-4 underwent a rapid and wide distribution in the tissues throughout the whole body within the time course examined. TCA precipitated radioactivity in kidneys was the highest, however, only trace amounts of [125I]exendin-4 was detected in the brain.

Based on the principle of progressive comprehensive comparability, must be similar to reference drugs in terms of physicochemical properties, bioactivity, pharmacokinetics, efficacy, and safety (including immunogenicity). The objective of the immunogenicity assessment of biosimilars is to assess potential differences in the incidence and severity of human immune responses between biosimilars and reference drugs. No clinically significant differences in immune responses between the two products is a key factor in demonstrating biosimilarity. The influencing factors include subjects, sampling scheme, product factors and bioanalysis methods. An important issue in bioanalysis is the selection of two-assay (based on biosimilars and reference agents respectively) or one-assay (based on biosimilars respectively) as the best method for comparative immunogenicity assessment. In order to support the development of biosimilars, this paper focuses on the use of One-assay to evaluate immunogenicity based on biosimilars. The development and validation of an ADA assay for biosimilar drugs should include all validation of the original drug. In addition, biosimilars need to be compared with reference to confirmation thresholds, antigenic equivalence, and drug tolerance to assess the ability of biosimilars and reference drugs to bind in a similar manner to positive controls. ADA data analysis should be combined with PK/PD parameters and clinical events.