How Biosimilars Are Approved

In highly regulated markets, biosimilars will be approved based on robust data packages that demonstrate similar patient efficacy, safety, and immunogenicity profiles as reference products.1

Around the world, biosimilar approvals have areas of distinction. In the United States, Europe, Japan, Canada, and Australia, regulatory authorities will require developers to meet high quality, safety, and efficacy standards between a biosimilar and the reference product. More specifically, they will require robust analytical, non-clinical, and clinical studies.1-3

Together, the analytical, non-clinical, and clinical data studies form the “totality of evidence” on which many regulatory authorities will base an approval decision. Therefore, they are important to the regulation of biosimilars.1

The right package of analytical data that proves critical quality attributes of a biosimilar have been matched to the reference product needs to be reviewed along with the non-clinical and targeted clinical data package. Regulators will use the total data package to make two key decisions:1

  1. Whether to approve the biosimilar for patient use in the disease indications studied for the biosimilar
  2. Whether to approve the biosimilar with extrapolation to the specific set of disease indications listed in the full label of the reference product, including one or more disease indications not clinically studied for the biosimilar4

In the US, the FDA may also use the totality of evidence to determine whether to grant a biosimilar the designation of an interchangeable biologic, which is a separate standard than biosimilarity and requires additional evidence—including patient–switching studies—to achieve.1,4


  • Highly similar notwithstanding minor difference in clinically inactive components
  • No clinically meaningful differences in safety, purity, and potency between the biosimilar product and the reference product
  • Approved as a biosimilar, AND:
    • Expectation of same clinical results in any given patient
    • For a product that is administered more than once, no additional risk to safety or diminished efficacy as a result of switching or alternating

    Global Biosimilar Guideline/Regulation Development1,5,7,9-44

    Global Biosimilar Guideline/Regulation Development

    WHO On Biosimilars

    In 2009, the World Health Organization (WHO) developed a set of globally accepted standards to assure safety, efficacy, and quality of biosimilar medicines.5

    US FDA On Biosimilars

    The Biologics Price Competition and Innovation Act (BPCI Act) of 2010 created a pathway for biosimilars to be approved by the FDA.2

    EMA On Biosimilars

    The European Medicines Agency (EMA) was the first major regulatory agency to develop biosimilar guidelines (in 2005).6


    1. US Department of Health and Human Services. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. Accessed November 23, 2016.
    2. Kozlowski S. US FDA Perspectives on Biosimilar Biological Products. Presented at: 2014 Biotechnology Technology Summit; June 13, 2014; Rockville, MD.
    3. Conner J, Wuchterl D, Lopez M, et al. The biomanufacturing of biotechnology products. In: Shimasaki C, ed. Biotechnology Entrepreneurship: Starting, Managing, and Leading Biotech Companies. Waltham, MA: Academic Press; 2014:351-385.
    4. Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. 2016; 2:e000154.
    5. World Health Organization. Guidelines on evaluation of similar biotherapeutic products (SBPs). Accessed November 23, 2016.
    6. Alten R, Cronstein BN. Clinical trial development for biosimilars. Semin Arthritis Rheum. 2015;44:S2-S8.
    7. Desanvicente-Celis Z, Caro-Moreno J, Enciso-Zuluaga M, Anaya JM. Similar biotherapeutic products in Latin America. Regulation and opportunities for patients with autoimmune diseases. Biosimilars. 2013;3:1-17.
    8. Republic of the Philippines Department of Health. Adoption of the World Health Organization “Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs)” for the Registration of Biosimilar Products. Accessed November 30, 2016.
    9. Garcia R, Araujo DV. The regulation of biosimilars in Latin America. Curr Rheumatol Rep. 2016;18:16-24.
    10. Argentina National Administration of Drugs, Foods and Medical Devices (ANMAT). Disposition Number 7729. 2011.
    11. Generics and Biosimilars Initiative. Global biosimilars guideline development – EGA’s perspective. Accessed February 19, 2015.
    12. Brazil National Health Surveillance Agency Collegiate Board. Resolution RDC No. 55, December 16, 2010.
    13. Minister of Public Works and Government Services Canada. Guidance for sponsors: Information and submission requirements for subsequent entry biologics (SEBs). March 5, 2010.
    14. Republic of Chile Ministry of Health. Approved Technical Standard No. 170 About health records related to biotechnological products derived from recombinant DNA technology. August 21, 2014.
    15. Ropes and Gray Alert. China Life Sciences. China announces final biosimilars guideline. Accessed  April 7, 2015.
    16. Colombia Ministry of Health and Social Protection. Pharmacological evaluation of biological drugs. 2014.
    17. Generics and Biosimilars Initiative. Regulation of similar biotherapeutic products in Latin America. Accessed February 19, 2015.
    18. Republic of Cuba Ministry of Public Health and Control of Medicines. Requirements for registration of known biologics. Regulation No. 56. 2011.
    19. Dominican Republic Chamber of Deputies. Proyecto De Ley Que Regula El Registro De Medicamentos Biológicos Biotecnológicos Y Biosimilares Para Uso Humano En La República Dominicana. Accessed October 17, 2016
    20. Egypt Ministry of Health. Draft guideline for registration of biosimilar products. June 12, 2012.
    21. European Medicines Agency. Committee for Medicinal Products for Human Use. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues. February 22, 2006.
    22. European Medicines Agency. Committee for Medicinal Products for Human Use. Guideline on Similar Biological Medicinal Products. October 30, 2005.
    23. Guatemala Ministry of Public Health and Social Services. Registro Sanitario de Referencia de Productos Biologicos y Biotecnologicos. January 5, 2015.
    24. India Department of Biotechnology, Central Drugs Standard Control Organization. Guidelines on similar biologics: regulatory requirements for marketing authorization in India. 2012.
    25. Iran Ministry of Health and Medical Education. Regulations on biosimilar drugs. January 11, 2010.
    26. Reinhold Cohn Group, Intellectual Property Attorneys. A new policy regarding the registration and use of bio-similar pharmaceuticals in Israel. Accessed February 19, 2015.
    27. Japan Ministry of Health, Labor and Welfare. Guideline for the quality, safety, and efficacy assurance of follow-on biologics. March 4, 2009.
    28. Jordan Food & Drug Administration. Guidance for registration of biosimilars. November 24, 2013.
    29. Ministry of Public Health, Republic of Kazakhstan. The approaches to the regulation of biological medicinal products in the Republic of Kazakhstan. Accessed February 19, 2015.
    30. Korea Food and Drug Administration. Guidelines on the evaluation of biosimilar products. 2009.
    31. Generics and Biosimilars Initiative. Mexico issues rules on biolimbos. Accessed October 13, 2016.
    32. Moldova Ministry of Health. Order No. 739: Regulation on the Marketing Authorization of Medicinal Products. July 23, 2012.
    33. Nigerian Law Intellectual Property Watch. Guidelines for the registration of biosimilars in Nigeria. Accessed February  19, 2015.
    34. Generics and Biosimilars Initiative. Peruvian guidelines for productos biológicos similares. Accessed February 19, 2015.
    35. Republic of Philippines Department of Health. Administrative Order 2014-0016. Adoption of the World Health Organization “Guidelines on the evaluation of similar biotherapeutic products (SBPs)” for the registration of biosimilar products. April 11, 2014.
    36. Saudi Food & Drug Authority. Guidelines on biosimilars. Version 1.1. December 12, 2010.
    37. Generics and Biosimilars Initiative. Singapore guidelines for biosimilars. Accessed February 19, 2015.
    38. Department of Health, Medicines Control Council, Republic of South Africa. Biosimilar medicines quality, non-clinical, and clinical requirements. March 2012.
    39. Taiwan Department of Health. Guideline on the examination and registration of drugs –guideline on biosimilar products. November 21, 2008.
    40. (Draft) Guidelines for Regulating Biosimilars in Thailand, Circular. April 2, 2012.
    41. Generics and Biosimilars Initiative. Turkish guidelines for biosimilars. Accessed February 19, 2015.
    42. Ministry of Health of Ukraine. Order No. 3: Orders pertinent to registration of medicinal products. April 1, 2013.
    43. Uruguay Ministries of Health, Foreign Affairs, Economy and Finance, Industry, and Labor and Social Security. Decree No. 324/999-12. Registro de Medicamentos Biotechnologicos. January 27, 2015.
    44. Venezuela National Division Control of Biological Products. Standard for health registration and pharmacovigilance similar products biotherapeutics in the Bolivarian Republic of Venezuela. June 12, 2012.