Copy biological approvals in China, compared to the US and EU

A review of copy biological approvals in China finds that 75% of approved monoclonal antibodies, fusion proteins and granulocyte colony-stimulating factor (G-CSF) copy biologicals have been successfully commercialized in the country [1].

The first copy biological approved in China was Hanlikang, a rituximab copy biological developed by Shanghai Henlius Biopharmaceutical Co Ltd (Henlius), which was commercialized in February 2019.

Henlius have had successful collaborations with the EU, which has approved its copy biologicals facility in China [2]. The European Commission also granted marketing authorization for Henlius’ trastuzumab biosimilar Zercepac, making it the first China-made biosimilar to receive approval in Europe [3].

Since the launch of Hanlikang, a total of four copy biologicals have been approved in China. All are monoclonal antibodies [4]. The regulatory body for the approval of medicines in China is the National Medical Products Administration (NMPA).

An article by L Zhang offers a review of the accessibility of copy biologicals in China, compared to biosimilars in the EU and US. The article focuses on monoclonal antibodies, G-CSFs and etanercept.

The EU was the first to approve a biosimilar in 2006 with Omnitrope (somatotropin) [5], followed by the US which approved Zarxio (filgrastim) in 2015 [6].

The EU approved a record number of 14 biosimilars in 2018, with the US Food and Drug Agency (FDA) slowly increasing its biosimilar approvals to reach a peak of 10 approvals in 2019. 2019 was also a record year for China, as the country’s first copy biological was approved in this year.

The article compares the accessibility of specific copy biologicals/biosimilars in China, the EU and US, see Table 1.

Table 1: Approval times in EU, US and China
Drug	EU approval date	Total approved in the EU	FDA approval date	Total approved in the US	NMPA approval date	Total approved in China
Adalimumab	2017	6	2016	5	2019	2
Bevacizumab	2018	2	2016	2	2019	1
Rituximab	2017	2	2017	2	2019	1
Infliximab	2013	4	2018	4	-	-
Trastuzumab	2015	5	2017	5	-	-
Etanercept	2016	2	2016	2	2005*	3
Pegfilgrastim	2018	6	2018	3	-	-
Filgrastim	2008	9	2015	2	-	-
*The etanercept copy biological Yisapiu was approved in China in 2005, before the originator drug.

The article also provides the same information, but for commercialization, see Table 2.

Table 2: Commercialization times in EU, US and China
Drug	EU commer-cialization date	Total commer-cialized in the EU	FDA commer-cialization date	Total commer-cialized in the US	NMPA commer-cializatiom date	Total commer-cialized in China
Adalimumab	2018	5	2023	1	2019	1
Bevacizumab	2022	0	2019	1	2019	1
Rituximab	2017	2	-	1	2019	1
Infliximab	2015	3	2016	0	-	-
Trastuzumab	2018	2	2019	0	-	-
Etanercept	2029	0	2029	3	2005*	3
Pegfilgrastim	2018	3	2018	0	-	-
Filgrastim	2008	9	2015	0	-	-
*The etanercept copy biological Yisapiu was approved in China in 2005, before the originator drug.

In summary, the EU has a total of 36 approved biosimilars of monoclonal antibodies, fusion proteins and G-CSF, while the US has 25, and China 4.

Although the proportion of successfully commercialized copy biologicals/biosimilars is highest in China compared to the EU and US (75% compared to 70% and 44%, respectively), this figure is falsely high in China due to the small number of approved copy biologicals.

Yet, China has achieved rapid commercialization of its copy biological relative to other nations. The availability of copy biologicals has also significantly reduced prices in China. For example, Hanlikang (rituximab) is 42% cheaper than the originator drug Rituxan in China, while the Humira and Avastin copy biologicals Anjianning and Ankeda reduced prices by 11% and 16%, respectively.

Editor’s comment
European Medicines Agency regulatory requirements ensure the same high standards of quality, safety and efficacy for biosimilars as for originator biologicals, and also include a rigorous comparability exercise with the reference product but they are not universally accepted by regulatory bodies outside of the European Union (EU). It should be noted that copy biologicals approved in China might not have been authorized if they had been subjected to the strict regulatory processes required for approval of biosimilars in the EU.

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References
1. Zhang L. A comparison of the biosimilar accessibility of China, the EU, and the U.S.: China’s biosimilars commercialized at an impressive speed [Internet]. 2020 Jun. [cited 2020 Nov 13]. Available from: https://flbook.com.cn/c/5GrJTeke2j#page/39
2. GaBI Online - Generics and Biosimilars Initiative. EU approves Henlius copy biologicals facility in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Nov 13]. Available from: www.gabionline.net/Biosimilars/General/EU-approves-Henlius-copy-biologicals-facility-in-China
3. GaBI Online - Generics and Biosimilars Initiative. EC approval for trastuzumab biosimilar Zercepac [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Nov 13]. Available from: www.gabionline.net/Biosimilars/News/EC-approval-for-trastuzumab-biosimilar-Zercepac
4. GaBI Online - Generics and Biosimilars Initiative. Copy biologicals approved in China [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Nov 13]. Available from: www.gabionline.net/Biosimilars/General/Copy-biologicals-approved-in-China
5. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Nov 13]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
6. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Nov 13]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US

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