Regulatory Update: Biosimilars in China

Biosimilars in China

BY Zeck Huang, Senior Consultant, Gopala Krishna, Principal Consultant, & Partha Roy, Vice President, Technical, Parexel - 11.27.19

In February 2019, National Drug Regulators in China approved the country’s first ever biosimilar product referencing Rituxan, a monoclonal antibody[1].  This biosimilar product, HLX01 (Hanlikang), was developed by Shanghai Henlius Biopharmaceutical (Henlius), and is indicated primarily for use in the treatment of non-Hodgkin’s lymphoma.  This approval signaled the beginning of the Biosimilar boom in China.

China has huge unmet medical need for biologics due to strict regulations and high cost incurred in new biologics.  Biosimilar drugs appear to be the best alternate solution for improving access to such life-saving biologics for Chinese patients and, potentially, lowering costs for both drug developers and for the waiting patient. 

In the face of the supportive pharmaceutical industry policies, biosimilar drug development in China is riding on an upward trend.  Since 2010, for nearly a decade, Chinese biotech companies started to develop the biosimilar drugs and built up a significant product pipeline.  China currently has more than 200 clinical trials approved for biosimilars and has more biosimilar drugs in the pipeline than any other country in the world.

In China, local biotech companies are the powerhouse for biosimilar development. While in the United States (US) and the European Union (EU), big pharmaceutical companies, such as Pfizer and Novartis, dominated the biosimilar market.  To date, several companies emerged as the powerhouse for biosimilars in China, such as Henlius, Innovent, Bio-Thera, and Hisun Pharma.

For example, Henlius has a total 10 biosimilars in their product pipeline[2], including products in preclinical stage to a product in the market. HLX01 was launched in China during 2019 soon after its approval.  HLX02 (Herceptin biosimilar) and HLX03 (Humira biosimilar) have been submitted to the Center for Drug Evaluation (CDE) for regulatory review.

In addition to local biotech companies, foreign companies are entering the biosimilars market in China via partnership with Chinese biotech companies.  Amgen has established a Biosimilar strategic alliance with Simcere (a local biotech company in Nanjing, China) to co-develop and commercialize biosimilars in China with a focus in the inflammation and oncology areas[3].  Samsung Bioepis, a partnership between Samsung Biologics and Biogen, will partner with Chinese Biopharmaceutical company 3SBio to develop and commercialize multiple biosimilars in China, including SB8, a proposed bevacizumab biosimilar referencing Avastin[4].

Due to the late start, regulations of biosimilars in China are not as well developed as those in US and EU.  The rise of China as a potential biosimilars powerhouse demands the regulatory agency in China to create a better-defined regulatory pathway that will reduce time to market, increase therapeutic options, and reduce costs. Regulatory agency in China can learn and adapt the regulatory guidelines created by EU and US FDA.  As a first step, China seems to align its regulatory framework with those of US and EU.

In 2015, the Chinese CDE released the first and final guidance for biosimilars, “Technical Guidelines for R&D and Evaluation of Biosimilars (Trail)”, providing a framework regarding the future of biosimilars in China.  These guidelines establish the principles for research, development, and evaluation of biosimilars. Based on the guidelines, a biosimilar drug is similar in quality, safety, and efficacy and should have the same amino acid sequence as the originator product.  Recently, CDE published a Q&A to clarify seven common and important questions, including:  reference drugs, comparability studies, immunogenicity, etc.

However, there are some unique requirements for Biosimilars in China.  For example, CDE does not accept an innovative biologic approved by foreign regulatory authorities as a reference product.  The reference drug must be approved by CDE at the time of the comparative clinical studies by the biosimilars and cannot be another biosimilar, even if approved by CDE.  EMA and FDA permit products approved outside their boundaries to be used as reference products following bridging studies.

For the moment, there is not clear legislation regarding naming of biosimilars in China.  The United States and the European Union have clear visions on naming, with the premises of those systems being to help patients benefit from a competitive and safe biosimilars market.

US FDA has created a new regulatory approval pathway, 351(k), for biosimilars, which are biologic drugs that are very similar to already approved “reference” biologics in terms of potency, safety, and efficacy, but are manufactured by different companies.  In China, sponsors applied for Biosimilars following regular new drug application procedure.  In the application form, however, the sponsors need to include a statement to the effect: “This product has been researched, developed, and reported as a biosimilar drug”.

Currently, in China, there is no overall harmonized regulatory approach on interchangeability.  US FDA recently published a guidance on interchangeability with a reference product[5].  This guidance has a critical impact on access to drugs for patients and physicians and on market size for biosimilar manufacturers.  It allows the reference product to be substituted with a biosimilar drug without the intervention of the health care provider.

Extrapolation of indication is allowed in China on a case-by-case basis and must be supported by all the scientific evidence generated in comparability studies (quality, nonclinical, and clinical).  Extrapolated indications must be those of the same clinically associated pathological mechanism and/or associated receptors, and of the same action mechanism and same targets.  A cautious approach should be taken when extrapolating indications for a combined therapy population, a population with different concomitant diseases, or a population with varied recommended doses.  This aligns with US and EU extrapolation pathways.

Taken together, combining rapidly increasing demand, the expiration of patents on many blockbuster biologics, better-defined regulatory pathways, and technological innovations closing technology gap, the biosimilar market in China will enjoy tremendous growth over the next 5-10 years.

Parexel is a leading CRO providing the regulatory support in preparing and filing biosimilar applications globally, including, but not limited to, the US, EU and Japan.  To help address potential challenges in the regulatory pathways, as applicable to Asian countries, particularly for China, Parexel has created a regulatory talent center in China.  The primary aim of this effort is helping local and international clients seamlessly in interfacing with regulators so worthy molecules are brought from bench to the bedside to make a difference. 


[1] https://www.centerforbiosimilars.com/news/china-approves-its-first-biosimilar-henlius-rituximab

[2] http://www.henlius.com/en/Product.html. Accessed on Oct 20, 2019.

[3] http://en.simcere.com/index.php/Index/news_detail/id/51

[4] https://www.centerforbiosimilars.com/news/eye-on-pharma-samsung-bioepis-to-partner-with-3sbio-on-biosimilars

[5] Considerations in Demonstrating Interchangeability with a Reference Product Guidance for Industry. May 2019


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