The Rise of Model-informed Drug Development in China

The Rise of Model-informed Drug Development in China

China’s pharmaceutical market is poised for growth. By 2020, it is expected to grow to approximately $120 billion. Today, China’s 1.36 billion people represent 20 percent of the world’s population. Yet, they comprise only 1.5 percent of the global drug market. From a demographic perspective, nine percent of the Chinese population today is over 65 years of age. The “greying of China” means the number will rise to 25 percent by 2050. Elderly patients currently comprise 23 to 40 percent of the prescription drug market in China and 40-50 percent of the over-the-counter drug market. These trends obviously present significant challenges for the Chinese and global pharmaceutical industry.

A push for innovation

The slow regulatory review process in China is an obstacle to pharma innovation. During the past several years, the China Food and Drug Administration (CFDA) amassed a huge backlog of drug applications. While the average review time was three years, some companies waited as long as eight years for their drug to be evaluated. That delay was due in part to staff shortages, but also to the large numbers of applications being submitted for generic drugs of inferior quality.

However, the CFDA is now working to expedite the drug approval process. They reviewed 9,394 new drug applications in 2015—a 90% increase from 2014. The “class of 2015” included approvals for 241 registration applications for marketing small molecule drugs, 76 for traditional Chinese medicines and natural medicines, and 25 for biological products.

In addition to developing new drug registration and approval guidelines, the CFDA is opening a second drug evaluation center in Shanghai to support its main office in Beijing. Shanghai is the financial center and largest city in China. It offers a highly-skilled local workforce and a transportation hub with strong rail and air connections.

Pharma research and development (R&D) is at a relatively early stage in China. There is significantly less financing, fewer assets, and a smaller number of high-quality drug candidates to support this market segment than in the US, Western Europe, or Japan. Most importantly, the expertise in drug development and the ability to navigate the regulatory landscape are just emerging as necessary competencies in China.  Having more experienced R&D professionals that understand drug development, have a global perspective, and can talk the same language as Western partners will help fuel the growth of the Chinese pharmaceutical market.

Increasing use of modeling and simulation

The Chinese Government’s growing interest in developing novel pharma products is fueling the adoption of modeling and simulation—also known as model-informed drug development—technologies. Model-informed drug development includes both “top-down” pharmacokinetic and pharmacodynamic (PK/PD) modeling and simulation and “bottom-up” physiologically-based pharmacokinetic (PBPK) modeling and simulation.

PBPK is used to determine first-in-human drug doses, predict drug-drug interactions, and understand drug disposition in untestable populations such as pediatric patients, pregnant women, and patients with co-morbidities or impaired organ function. It can also help select dose regimen, assess food effects on oral medicines, and evaluate the impact of disease and lifestyle factors on drug disposition.

Generic drugs are the mainstay of China’s pharma industry, representing 80 percent of all drug sales in 2015. Thus, generics companies need only to show that their products were accurate reproductions of brand drugs. As a result, they tended to conduct only bioequivalence and non-compartmental analyses (NCA). The CFDA employs Phoenix software to conduct those types of analyses. The Phoenix platform is used to manage, analyze and report PK, PD, and toxicokinetic (TK) data.

This TK and PK/PD analysis approach is now being used by pharma companies, clinical research organizations, academic centers, and hospitals. Pharmacometrics organizations and associations are also being founded in Beijing and Shanghai to help educate local scientists in this field. Attendance in pharmacometrics training courses is also increasing each year.

Several top academic institutions, such as Peking University, Peking Union Medical College Hospital, China Pharmaceutical University, Huashan Hospital, and Fudan University provide valuable support to industry. Peking University was recently established as a Phoenix Center of Excellence. This Center of Excellence Program is designed to enhance research and training in pharmacometrics at elite academic centers globally. Phoenix software and licenses have been donated to Peking University for teaching and research purposes. The institution also receives associated training and workshop assistance. The program goal is combining Peking University’s research, clinical, and educational expertise with Phoenix IT infrastructure to create innovative approaches to improving population health.

As more Chinese pharma companies develop innovative products, they have started to use PK/PD modeling and simulation to make data-driven decisions at all stages of drug development. This quantitative framework includes dose selection, clinical trial design, competitive analysis, and a range of safety and efficacy factors.

Of the 45 drugs approved by the US FDA in 2015, more than 90 percent leveraged model informed drug development to support their labels. Using this approach will help bring safer therapies to market faster and support China’s fast-track drug approval process.

Future outlook

Pharma innovation will continue to increase in China as product differentiation grows in importance. In the next five to 10 years, China is expected to develop several first-in-class or best-in-class pharmaceutical products. Consequently, the percent of generics on the Chinese market will decrease and the number of novel new drug applications will increase.

Biologics, especially biosimilars and bio-betters, will flourish in China. Many companies are already establishing good manufacturing practices (GMP), manufacturing capabilities, and developing biosimilars that target current blockbusters, such as Humira, Rituxin, and Herceptin. Usually five to 15 competitors apply for regulatory approval for each target with the goal of selling these Chinese biosimilars in other regulated markets.

China’s new policies show its commitment to being an active participant in global drug development and in commercializing innovative products. That’s why I’m excited to help support pharmaceutical innovation by leading Certara Strategic Consulting China (CSCC) in Shanghai. Our scientists will provide strategic pharmacometric services to biopharm companies, nonprofits, and regulatory agencies. The CSCC headquarters are located close to the CFDA’s new drug evaluation center.  Because our office is based in a free trade zone, we have special tax benefits and can easily perform financial transactions between China and the US.

By embracing modeling and simulation technology and instituting a more business-friendly climate, the Chinese drug development market today has unprecedented opportunities. The next decade will be our strategic opportunity period.

Learn how Certara’s model-informed drug development solutions can help you!

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To learn about China’s push for innovation in drug development, read this article in Outsourcing Pharma.

Christine Yuying Gao

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Christine Yuying Gao

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Dr. Christine Yuying Gao is a trained anesthesiologist and clinical pharmacologist with more than 100 published books, manuscripts, and abstracts and 20 years of modeling and simulation experience in optimizing treatment and bridging strategies, trial designs, and drug development decision-making. Dr. Gao conducted her postdoctoral fellowship in clinical pharmacology at the Department of Anesthesia, Stanford University School of Medicine. She received her PhD in clinical pharmacology from the Jiaotong University School of Medicine and her MD in medical science from the Shanxi Medical University in China.