The 2nd China Bioanalysis Forum Annual Conference: clinical bioanalysis and large molecule bioanalysis

Beijing, China, 7–8 June 2014.

The second China Bioanalysis Forum (CBF) conference was successfully held in Beijing, China, in June 2014 and covered the theme of clinical bioanalysis and large molecule bioanalysis. Compared with the first conference in 2013, this conference was attended by scientists from a greater number of scientific disciplines and geographic areas. This report summarizes the major topics in the conference as well as the future plan of the CBF.

The China Bioanalysis Forum (CBF), a nonprofit bioanalysis-focused organization in China, was formed in September 2012 by a group of scientists who shared the same passion to accelerate the advancement of bioanalytical science in China. The CBF mission is to encourage the scientific interaction between academia and industry in the field of bioanalysis in China, to promote the harmonization of Chinese-regulated bioanalytical guidelines with international bioanalytical guidelines, to promote the execution of regulated bioanalysis in China based on the industrial best practice, to actively participate in the harmonization and globalization of international guidance, and to provide scientific education, technical training and talent development for local young scientists. The CBF organized its own annual conference with the aims of exchanging information and network building among experts from academic institutes, clinical research, pharmaceutical/biotech industry, contract research organizations (CRO) and regulatory agencies. The first CBF annual conference was successfully held in Shanghai, China, in April 2013.

The second CBF annual conference was held at Peking University Health Science Center in Beijing on 7–8 June, 2014, in which more than 200 delegates from 16 cities and/or provinces attended. The theme of this conference was clinical bioanalysis and large molecule bioanalysis. The conference was arranged in a way that all scientific discussions were held on the first day for all attendees followed by a focused group meeting for members from Expert Committees and Steering Committee on the second day to discuss the upcoming China Pharmacopeia guidance on bioanalytical method validation (BMV), the collaboration between the CBF and the Chinese Food and Drug Administration (CFDA), and the future plan for 2014–15 and beyond.

Summary of CBF activities

Zhong (Shanghai Institute of Materia Medica, China), chair of the 2nd CBF conference, first gave a warm welcome to all conference attendees. He emphasized the urgent needs to establish a bioanalysis-focused organization such as the CBF to support the fast growth of Chinese drug research and development, and the potential roles that the CBF can play in this important area.

Next, Tang from ICON (co-chair of the conference) reviewed what CBF had achieved since its inauguration in late 2012 and these are discussed below.

• Regulatory activities:

  • CBF Expert Committee (EC) participated in the first independent BMV draft guidance of the Chinese pharmacopeia (version 2015). The guidance (in Chinese) will be posted on the Chinese pharmacopeia website for public review soon;

  • CBF provided its feedback to the US FDA draft guidance for industry on bioanalytical method validation, issued in September 2013; 13 of the CBF EC members attended the most recent Crystal City V meeting in Baltimore, MD, USA, in December 2013 and participated in the lively discussions;

  • Several CBF EC experts participated in site audits for Chinese clinical bioequivalence (BE) studies organized by the CFDA.

• Conferences/workshops:

  • CBF organized the first (2013) and the second (2014) annual conferences;

  • Members of the CBF were invited to the annual conferences of the European Bioanalysis Forum to give presentations on global harmonization of bioanalytical regulations and Chinese clinical research;

  • Members of the CBF participated in the discussion of global harmonization of bioanalytical regulations at conferences held by the Japan Bioanalysis Forum;

  • CBF coorganized the Regulated Bioanalysis Session on CPSA Shanghai conference in 2013;

  • CBF will cosponsor the ‘Meet the Dragon’ workshop with the European Bioanalysis Forum in September 2014 to discuss the Chinese regulations of bioanalysis and the current status of Chinese early/later phase clinical research.

• Publications:

  • CBF is in the process of publishing a series of white papers to interpret the new Chinese pharmacopeia guidance on bioanalytical method validation.

Bioanalysis in clinical studies

Hu (Peking Union Medical College Hospital, China) presented a review on the roles of clinical Phase I research in drug research and development. She gave the audience practical advice on how to establish a good Phase I unit in China based on international and domestic regulations. She also discussed the design of the first-in-human studies based on preclinical data using various modeling tools. Finally, Hu elaborated on the design of the first-in-human studies using a case study of CPRC1, a new DPP-4 inhibitor. This lecture provided the attendees (most of whom were bioanalytical scientists) with an excellent overview on how the data obtained from a bioanalytical laboratory could be applied in a clinical pharmacology study.

Wei (Institute of Clinical Pharmacology of Peking University, China) shared his experience of conducting clinical pharmacology studies. He encouraged further improvement of regulated bioanalysis quality in China. One of the examples he gave was the data for BE studies of amlodipine submitted from 17 sponsors showing highly variable AUC results. He reiterated that bioanalysis in a regulated environment was the key for obtaining good quality data. Finally, he shared his personal experience of what a CFDA reviewer’s concerns were in the evaluation of analytical reports.

Large molecule bioanalysis

Song gave a presentation entitled ‘Bioanalytical strategy in the R&D process of biosimilar products’. Among the top eight biologics with regard to revenue, six are monoclonal antibody products. It is inevitable that the development of biosimilar products became the center of drug R&D activities in pharmaceutical companies in many countries, including China. He discussed the popular topic of ‘how similar is similar?’ and explained that, instead of safety and efficacy, the challenges for analysis and bioanalysis were the similarity and comparability between the original biologics and biosimilar products. In his presentation, different platforms for immunoassay such as ELISA, ECL, Gyros, SPR and AlphaLISA were compared. The method development and validation for ligand-binding assays and immunogenicity assays were also discussed in detail. In another presentation, Li (Wuxi AppTec, China) expressed her views on considerations when developing anti-drug antibody (ADA) assays. She summarized different causes of immunogenicity, platforms for developing ADA assays, multi-titer approaches in method development, selection of critical reagents and development of neutralizing antibody assays. Finally, she compared the requirements of pharmacokinetic, ADA and neutralizing antibody assays.

Bi (Covance China) discussed challenges in peptide analysis by LC–MS/MS, such as sensitivity requirement, instrument carryover, nonspecific binding, protein binding, matrix effect to internal standard and analyte, optimization of extraction procedure and interference from endogenous substances. He illustrated his strategies in the stages of MS tuning, sample processing and extraction, chromatography column and LC mobile phase selection, needle washing, selection of solid phase extraction with different chemistry and finding an appropriate internal standard. With these strategies, Bi showed a case study in which a LLOQ of 50.0 pg/ml for a therapeutic peptide was achieved.

Regulatory updates

Zhang (Center of Drug Evaluation, CFDA) introduced a new requirement for all approved clinical trials (including BE and pharmacokinetic Phase I–IV trials) to be registered and published on a CFDA information platform (www.cde.org.cn). This new requirement would allow the CFDA to strengthen the oversight of all clinical trials, make the information of these trials more transparent, and protect the safety and interests of the patients/healthy volunteers in the trials. Zhang also provided regulatory updates on the FDA guidance on Bioequivalent (BE) and Bioavailability (BA) studies as well as his experience of evaluating BE/BA submissions, especially those for extended released products. He mentioned that the Guidance of Handling and Storage Requirements for Test Articles during BE/BA research had been completed and in the process of final approval by the CFDA.

Another CFDA representative Sun gave an update on the most recent Guidance for Non-clinical Pharmacokinetic Research on Drugs. The revision of the new guidance was initiated in April 2012, published on the CFDA website for public comments in May 2013, finalized in July 2013 and put into effect in May 2014. The new guidance would cover traditional Chinese medicines and natural products besides chemical drugs. For traditional Chinese medicines and natural products, research on toxicity of active components and active metabolites was required. For bioanalysis, the guidance added new requirements on dilution integrity and carryover. The requirement of using immunoassays for nonclinical research was excluded. For tissue analysis, only one or two representative tissues were required for method validation. Quality controls for other tissues were added during sample analysis with the standards prepared in the representative tissue blank. During onsite audits, all chromatograms and original data for all sample analysis were required to be ready.

Young scientists presentations

One of the highlights of the conference was the participation from young scientists who gave the following six presentations:

• Bioanalytical method development using LC/MS/MS and its application for bisphosphonates compounds in plasma (Yang, SIMM);

• Chiral separation and stereoselective pharmacokinetic evaluation of three new anticholinergic drugs (Li, Academy of Military Medical Sciences, China);

• Bioanalysis of three neurotransmitters in rat brain microdialysate (Li, ChemPartner);

• Pharmacokinetic study and active metabolite screening of two major anticancer capilliposide components in Lysimachia capillipes Hemsl (Cheng, Huazhong University of Science and Technology, China);

• Evolving journey of biomolecule quantitation using LC–MS/MS (Li, GSK, China);

• Bioequivalence study for high variable drug products and aspects to consider in bioanalysis (Liu, Beijing Aerospace Central Hospital, China);

The interactive Q&A session after each presentation provided excellent scientific discussion and learning opportunities for young scientists.

Panel discussion

Five renowned scientists and CFDA representatives (Zhong, Hu, Song, Sun and Zhang) participated in an interactive panel discussion with all conference attendees. Discussion topics included: what are the recent hot areas in bioanalysis?; what are the new challenges in the bioanalysis of large molecules, biomarkers and clinical studies?; what are the potential solutions?; from the perspective of regulatory review, what are the main issues in bioanalysis?; and we have many young bioanalytical scientists today, do you have any suggestions in terms of their career development?”. The panel discussion also followed with a Q&A session from the audience. Various questions ranging from regulatory to technical issues were raised and discussed.

CBF future plans