Regulation of copy biologicals in China

Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(2):75-6.
DOI: 10.5639/gabij.2018.0702.015

Published in: Volume 7 / Year 2018 / Issue 2
Category: Regulatory
Page: 75-6
Visits: 6623 total, 1 today
Keywords: biological, China, copy biological, regulation

The first draft guidelines for copy biologicals were introduced in China back in 2014. The Technical Guideline was then updated and finalized in 2015. In this paper, how the Drug Registration Regulation (2007) pathway classifies therapeutic biologicals and the principles and challenges of the copy biologicals guideline are described.

Submitted: 3 May 2018; Revised: 8 May 2018; Accepted: 15 May 2018; Published online first: 25 May 2018


China has a huge market for copy biologicals, with 40% of China’s US$1.5 billion recombinant biologicals sales coming from copy biologicals, which have enjoyed compound annual growth rate (CAGR) of approximately 25–30% over the past decade. With predicted market growth of 25% per year, the Chinese copy biologicals market is expected to grow to US$2 billion. This makes it an attractive market to move into for more and more multinational biosimilars makers.

China first introduced draft guidelines for copy biologicals back in 2014 [1]. The Technical Guideline was then updated and finalized in 2015 [2]. The legal structure of the current Chinese copy biologicals guideline is based on the Drug Administration Law (Revised 2015) issued by the Chinese Government and on the Drug Registration Regulation (Revised 2007) issued by the China Food and Drug Administration (CFDA).

CFDA (simplified Chinese: 国家食品药品监督管理局) has been the Chinese authority that oversees all drug manufacturing, trade and registration in the country since 2003 [2].

The Drug Registration Regulation (Revised 2007) pathway classifies therapeutic biologicals into 15 categories [3]:

  1. Products that have not been marketed in China and other countries
  2. Monoclonal antibodies
  3. Gene therapy, somatic cell therapy and related products
  4. Allergen products
  5. Multicomponent bioactive products extracted from human/animal tissue/body fluid, or produced by fermentation
  6. New combination products made from marketed biological
  7. Products which have been marketed in other countries but not China
  8. Microbiological products containing components made from strains that have not been approved for use in China
  9. Products that do not have the exact same structure as marketed products and have not been marketed in China or overseas (including locus mutation or absence of amino acid, changes in post-translational mutation or absence of amino acid, changes in post-translational modification caused by using different expression systems, and chemical modification of the product)
  10. Biologicals produced by different methods compared with the marketed products, such as different expression systems, or host cells
  11. The first product produced by recombinant DNA method (for example, replacement of synthesis, tissue extraction or fermentation technologies by recombinant DNA technology)
  12. Products changed from non-injection route to injection route or from topical use to systemic use, which have not been marketed in China or other countries
  13. Marketed products with a new formulation but same route of administration
  14. Marketed products with a new route of administration (excluding Category 12)
  15. Products with national standards

The Chinese copy biologicals guideline is based on four principles:

  • Comparison
  • Step-wise
  • Consistency
  • Similarity

These core principles should be used across the entire R & D and evaluation process, see Figure 1.

Figure 1

The updated and finalized Technical Guideline for copy biologicals [2] provides a relatively clear regulatory pathway for development of copy biologicals in China. It clarifies some confusion and provides the principles of R & D and evaluation for copy biologicals. It also helps to regulate activities and speed up the entire process. The guideline is also intended to raise the bar for entry into the copy biologicals field, avoiding low quality competition.

The Technical Guideline follows similar standards and principles as guidelines from other major markets. This, it is hoped, will increase the quality of products produced in the country and make them more competitive, as well as increase the possibility of marketing Chinese copy biologicals in other countries.

The main challenges with respect to the guideline include:

  • Significantly increased R & D costs
  • Availability of reference product for clinical trials
    – ‘reference product for clinical trials should be approved in China’
  • Basically impossible to waive phase III comparative trials
  • Extrapolation of indications limited to indications approved in China
  • Too general and impractical
  • Some requirements are too stringent

Editor’s comment

It should be noted that ‘copy biologicals’ approved in China might not have been authorized following as strict a regulatory process as is required for approval of biosimilars in the European Union. The 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.

Competing interests: None.

Provenance and peer review: Commissioned; externally peer reviewed.

Michelle Derbyshire, PhD, GaBI Online Editor

1. GaBI Online – Generics and Biosimilars Initiative. China to release biosimilars guidelines []. Mol, Belgium: Pro Pharma Communications International; [cited 2018 May 8]. Available from:
2. GaBI Online – Generics and Biosimilars Initiative. Chinese guidelines for biosimilars []. Mol, Belgium: Pro Pharma Communications International; [cited 2018 May 8]. Available from:
3. Hu H. Challenges & strategies to enter the emerging markets for biosimilars. Biosimilars Europe Congress; 22–23 November 2016; London, UK.

Disclosure of Conflict of Interest Statement is available upon request.

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