Author byline as per print journal: Hye-Na Kang1, PhD; Robin Thorpe2, PhD; Ivana Knezevic1, PhD; Daehyun Baek3, PhD; Parichard Chirachanakul4; Hui Ming Chua5; Dina Dalili6, PhD; Freddie Foo7, MSc; Kai Gao8, PhD; Suna Habahbeh9, PhD; Hugo Hamel10, PhD; Edwin Nkansah11, PhD; Maria Savkina12, PhD; Oleh Semeniuk13; Shraddha Srivastava14; João Tavares Neto15, PhD; Meenu Wadhwa16, PhD; Teruhide Yamaguchi17, PhD
The World Health Organization (WHO) has provided specific guidance for biosimilar products to assist regulators, manufacturers and other professionals involved in the development and evaluation of these products. The development and approval of biosimilars are important for health care, as they allow the marketing of safe, efficacious and affordable biological products. Since the first biosimilars were approved in the EU in 2006, a series of biosimilars have been approved in many countries/geographical regions. This manuscript provides the figures on the status of approved biosimilars in 16 countries based on the information from regulatory experts and from publicly available data. It is clear that increasing numbers of biosimilars are now available in many countries and provide more options for treatments. It is expected that adoption of biosimilars will allow affordable health care and greater patient access to important medicinal products. It will also contribute to the overall WHO goal recognized by the World Health Assembly in 2014 by adopting a resolution on access to biotherapeutic products including biosimilars and on ensuring their quality, safety and efficacy.
Submitted: 12 October 2020; Revised: 25 November 2020; Accepted: 25 November 2020; Published online first: 14 December 2020
Development of biosimilars is important for health care as it allows the marketing of safe, efficacious and affordable biological products. The European Medicines Agency (EMA) was the first regulatory agency to establish a process for the approval of biosimilars and approved the first biosimilars in 2006.
Since then, there has been much progress in establishing the regulatory pathway for biosimilars and a wide range of biosimilars have been approved for marketing in many countries/geographical regions . An extensive number of biosimilars are now being used globally and are contributing considerably to widening patient access to appropriate biological medicines at reduced costs.
The World Health Organization (WHO) has taken a lead in the biosimilar field at the global level and has developed specific guidance for biosimilar development and approval as well as a number of other pertinent guidelines [2-4]. WHO has also organized a number of implementation workshops to assist regional regulatory agencies and manufacturers in the biosimilars area. As part of these workshops, surveys have been conducted to understand the current situation with biosimilars in the participants’ countries [1, 5, 6]. These surveys provide a unique opportunity to establish the situation with currently marketed biosimilars/similar biotherapeutic products in 16 countries. This publication presents this information.
The survey was conducted as previously described , but the information was updated and confirmed in July 2020. The information contained in this survey report is from participants of 15 countries who agreed for their information to be disclosed. The feedback from the UK refers to the situation in the European Union (EU) rather than specifically for the UK. Information from the US was not derived from the survey, but from the website of the US Food and Drug Administration (FDA). It should be noted that biological products in Table 1 have been approved as biosimilars in the countries as surveyed, but biosimilars approved in certain countries might not have been approved following a strict comparative regulatory process as recommended by WHO guidelines. The term ‘approval’ used in the manuscript is referring to the approval by the national regulatory authority. WHO did not conduct assessment of these products nor of the procedure for regulatory evaluation conducted by the national regulatory authorities as a basis for the ‘approval’.
Table 1 shows a breakdown of information received which includes country participating (in survey), International Nonproprietary Name (INN), brand name and manufacturer/company name of product, the location of the producer of the product, the clinical indications approved, the reference product used and its manufacturer and the date the biosimilar/similar biotherapeutic products was approved. Table 2 shows the numbers of biosimilars/similar biotherapeutic products approved by regulatory authorities in the 16 countries (updated July 2020) specified by product type.
Following the EU’s lead after their first biosimilar approvals in 2006, other countries have approved biosimilars/similar biotherapeutic products not only with increasing numbers but also with expanding the available product classes. ‘Big pharma’, e.g. in the EU and the US, continues to dominate the biosimilar market, but local manufacturers have played a significant role in producing biosimilars/similar biotherapeutic products in some countries, e.g. in China, India, Iran, Japan, Republic of Korea.
When compared with the situation in August 2019 , the major biosimilar products being approved as of July 2020 are monoclonal antibodies. For example, six and seven monoclonal antibody similar biotherapeutic products/biosimilars have been approved in Brazil and in Canada, respectively, during the updating period.
The quality of similar biotherapeutic products/biosimilars approved in some countries is still an issue for concern. Some products in certain countries were approved prior to adoption of regulations or guidelines for biosimilar evaluation, see Table 1. As mentioned above, EMA was the first agency to adopt the biosimilar concept in 2006, so products called ‘biosimilars’ approved before 2006 are unlikely to be biosimilars . Regulators need to reassess such products to ensure whether they meet the current requirements and to identify the inappropriate labelling of non-innovator and copy-version products (approved when regulatory procedures were not well defined) as biosimilars [7-9].
It is clear that increasing numbers of biosimilars are now available in many countries and provide more options for treatments. In certain countries, the availability of various product classes has been expanded by approval of biosimilars for which product classes were not available on the market previously. This is important for relatively expensive products, e.g. monoclonal antibodies. It is expected that adoption of biosimilars will allow affordable health care and greater patient access to important medicinal products .
The authors alone are responsible for the views expressed in this manuscript and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated. The survey participants are listed in alphabetical order in the author section after the three primary authors.
The information in this manuscript provided based on the categorization of biosimilars by each national regulatory authority. Thus, biosimilars approved in certain countries might not have been approved following as strict a regulatory process as is required by WHO guidelines. Indications in Table 1 also as reported by survey participants; not necessarily representing WHO approval of these.
The World Health Organization retains copyright and all other rights (CC BY 3.0 IGO) in the manuscript of this article as submitted for publication.
The Ministry of Health and Welfare of Republic of Korea provided the fund to WHO for this project through a voluntary contribution for the period of 1 December 2018–30 September 2021.
Competing interests: The authors have disclosed no potential conflicts of interests.
Provenance and peer review: Not commissioned; externally peer reviewed.
Hye-Na Kang1, PhD
Robin Thorpe2, PhD
Ivana Knezevic1, PhD
Daehyun Baek3, PhD
Hui Ming Chua5
Dina Dalili6, PhD
Freddie Foo7, MSc
Kai Gao8, PhD
Suna Habahbeh9, PhD
Hugo Hamel10, PhD
Edwin Nkansah11, PhD
Maria Savkina12, PhD
João Tavares Neto15, PhD
Meenu Wadhwa16, PhD
Teruhide Yamaguchi17, PhD
1World Health Organization, Department of Health Product Policy and Standards, 20 Avenue Appia, CH-1211 Geneva, Switzerland
2Independent expert, Welwyn, UK
3Ministry of Food and Drug Safety, Osong, Republic of Korea
4Food and Drug Administration, Nonthaburi, Thailand
5National Pharmaceutical Regulatory Agency, Selangor, Malaysia
6Iran Food and Drug Administration, Tehran, Iran
7Health Sciences Authority, Singapore
8Shanghai University, Shanghai, People’s Republic of China
9Jordan Food and Drug Administration, Amman, Jordan
10Health Canada, Ottawa, Canada
11Food and Drugs Authority, Accra, Ghana
12Centre for Evaluation and Control of Medicinal Immunobiological Products of the FSBI «SCEEMP» of the Ministry of Health of Russia, Moscow, Russian Federation
13Ministry of Health of Ukraine, Kyiv, Ukraine
14Central Drug Standards Control Organization (CDSCO), Ministry of Health & Family Welfare, New Delhi, India
15Brazilian Health Regulatory Agency (ANVISA), Brasilia, Brazil
16National Institute for Biological Standards and Control, Medicines and Healthcare products Regulatory Agency, Potters Bar, UK
17Pharmaceuticals and Medical Devices Agency, Tokyo, Japan
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5. Kang H-N. Summary of the diverse situation of similar biotherapeutic products in the selected countries (August 2010). Biologicals. 2011;39(5):304-7.
6. Kang H-N, Thorpe R, Knezevic I, Casa Levano M, Chilufya MB, Chirachanakul P, et al. 2020. Regulatory challenges with biosimilars: an update from 20 countries. Ann N Y Acad Sci. 2020 Nov 21. doi: 10.1111/nyas.14522. Online ahead of print.
7. Recommendations. 14th International Conference of Drug Regulatory Authorities (CDRA); 30 November–3 December 2010; Singapore.
8. Kang H-N, Knezevic I. Regulatory evaluation of biosimilars throughout their product life-cycle. Bull World Health Organ. 2018;96(4):281-5.
9. WHO Expert Committee on Biological Standardization. Annex 3. Regulatory assessment of approved rDNA-derived biotherapeutics. WHO Technical Report Series no. 999, 2016 [homepage on the Internet]. [cited 2020 Nov 25]. Available from: https://www.who.int/biologicals/areas/biological_therapeutics/Annex_3_Regulatory_assessment_of_approved_rDNA-derived_biotherapeutics.pdf?ua=1
Author for correspondence: Hye-Na Kang, PhD, World Health Organization, Department of Health Product Policy and Standards, 20 Avenue Appia, CH-1211 Geneva, Switzerland
Disclosure of Conflict of Interest Statement is available upon request.
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