Lawrence A. Hill, PharmD, MBA, RPH, BCPS, provided an insider's view of the rapidly changing biologics and biosimilars market and regulatory structure in China.
Rapid health care reforms in China have led to a regulatory environment that improves conditions for biosimilar development and approval, according to Lawrence A. Hill, PharmD, MBA, RPh, BCPS. Hill is CEO of Gan & Lee Pharmaceuticals, a company specializing in the development and marketing of insulin products in Asia.
Hill, who spoke at the recent Festival of Biologics virtual meeting, said that biosimilars and China go well together because the country has a large “copy” culture in medicine. The country has 382 biologic drugs and vaccines, and just 21 of those are innovative or originator products, he said.
A Supercharged Biologics Market
China has supercharged the growth of its biologics industry with a massive health care reform begun in 2008. In 2003, according to the Chinese Ministry of Health, just 55% of urban residents and 21% of rural residents in China had insurance coverage. The reform program boosted coverage to 97% of individuals by 2015; however, according to Hill, many of the most expensive medicines still must be paid out-of-pocket. The difficulty many residents of China have in paying for modern medicine makes this a very price sensitive market, which also improves the potential for biosimilar uptake, owing to their cost advantages, he said.
Biosimilars are considered an “integral part” of China’s effort to achieve universal coverage, with the first biosimilar, for rituximab, approved in February 2019. The country has a population of 1.3 billion and its biologics market was the second largest by sales in 2017. This market is also growing fast, with a 16% compound annual growth rate (CAGR) from 2010 to 2021. The market for copy biologics is growing at a 25% CAGR, Hill said.
As a result of the modernization effort, China’s regulatory system for drugs is rapidly coming to resemble the frameworks that have been established in the United States and European Union, Hill said. Priority review for drugs with exceptional clinical value was established in 2016, followed in 2017 by many guidelines for easing acceptance of imported drugs, conditional approvals of urgently needed drugs, and an “orange book” for generic product standards.
Regulatory enhancements from 2018 cover fast approvals for urgently needed foreign drugs. “Companies that can provide evidence of a drug working equally well across races can immediately apply for marketing approval with existing data and be eligible for priority review,” Hill said. Guidelines for accepting overseas clinical trial data and a shortening of the regulatory review period leading to drug approval also came about in 2018. Companies can even move forward with clinical trials if China’s Center for Drug Evaluation (CDE) does not meet preset deadlines for responding with comments, Hill noted.
In 2015, the CDE published final technical guidance for the development and evaluation of copy biologicals. This established principles for research, development, and evaluation of biosimilars, and it defines a biosimilar along lines almost identical to those accepted in the United States and Europe, namely that the drug must be similar in quality, safety, and efficacy and should have an amino acid sequence that is identical to the originator product.
China Policy: Key Differences
There are some key differences. Chinese authorities almost always require a comparative clinical efficacy study for a biosimilar, something that regulators may request in the United States or European Union but which in those regions is increasingly considered of little value compared with other biosimilar development groundwork, such as structural and functional characterization and comparative analytical, nonclinical, and clinical stepwise evaluation.
China will not accept a reference product that has been approved by foreign regulators. By comparison, US regulators may accept a foreign reference product if bridging studies are done to demonstrate biosimilarity. There is no established interchangeability policy in China for the substitution of biosimilars for reference products at the pharmacy counter, and the country has no specific standard for biosimilar naming. In the United States, a system of suffixes is applied to approved biosimilars to aid in drug identification and real-world performance tracking.
“The biosimilar regulatory environment in China has been evolving extremely rapidly,” Hill concluded. This has occurred against a backdrop of “exceptionally aggressive” modernization of the pharmaceutical regulatory environment.
Entering the market is challenging for foreign companies, and Hill said the only route of entry for a foreign concern is to partner with a local biopharmaceutical company that can provide guidance and the sponsorship needed for foreign applications. “There are exceptional commercialization opportunities within China. Foreign products are being welcomed,” he said.
Amgen, of Thousand Oaks, California, is one of the outside companies that has taken the path of local sponsorship. In 2017, the company partnered with Simcere of Nanjing, China, to codevelop and distribute biosimilars in China for patients with cancer and inflammatory diseases. And in 2019, Samsung Bioepis, of Incheon, Republic of Korea, partnered with the Chinese biopharmaceutical company 3SBio to develop and commercialize biosimilars, including SB8, a bevacizumab biosimilar referencing Avastin.
Some Chinese companies are becoming biosimilar pioneers in their own right. These include Henlius, Innovent, Bio-Thera, and Hisun Pharmaceuticals. Henlius obtained the first biosimilar approval in China and has a large pipeline of products. The company most recently reported Chinese regulatory acceptance for HLX03, an adalimumab biosimilar for the treatment of rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis. This marks the third biosimilar approval in China for Henlius.
Hill’s company, Gan & Lee, was founded as Beijing Gan & Lee Biotechnology and developed the first recombinant human insulin (Gansulin) in China.