Quality Assurance Understanding Biologics
ASSESSING BIOSIMILARITY A Rigorous Biosimilar Development Pathway
ASSESSING BIOSIMILARITY A Rigorous Biosimilar Development Pathway

Demonstration of biosimilarity requires evidence that a biological product is highly similar to its originator product, notwithstanding clinically inactive components.1

THE DEVELOPMENT PATHWAYS FOR ORIGINATOR BIOLOGICS AND BIOSIMILARS ARE DIFFERENT2
DEVELOPMENT PATHWAY: ORIGINATOR BIOLOGIC VS BIOSIMILARS DEVELOPMENT PATHWAY: ORIGINATOR BIOLOGIC VS BIOSIMILARS CLICK ON A PYRAMID TO READ MORE ABOUT EACH PROCESS TAP ON A PYRAMID TO READ MORE ABOUT EACH PROCESS
 
 
 
Development Pathway for Originator Biologics
The development pathway of originator biologics serves to establish safety and efficacy of a new product.5
  • Analytical and animal testing is first performed to define the biologic’s pharmacologic and toxicologic effects before evaluation in humans4
  • A focus on clinical trials in development of an originator biologic is necessary to establish efficacy2,4
Development Pathway for Biosimilars
In evaluating biosimilars, the US FDA considers a “Totality-of-the-Evidence” approach.1
  • Extensive analytical testing of structure and function serve as the foundation of this approach1
  • Selective and targeted animal and human clinical studies support that there are no clinically meaningful differences between the biosimilar and the originator biologic1

Preclinical Studies

Clinical Development

Pharmacovigilance

Immunogenicity

Extrapolation

FDA, Food and Drug Administration; PD, pharmacodynamics; PK, pharmacokinetics.
References:
1. US FDA. Scientific considerations in demonstrating biosimilarity to a reference product. http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf. Published April 2015. Accessed June 3, 2016. 2. US FDA. Overview of the regulatory guidance for the development and approval of biosimilar products in the US. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM431118.pdf. Accessed June 3, 2016. 3. US FDA. Guidance for Industry. Providing clinical evidence of effectiveness for human drug and biological products. http://www.fda.gov/downloads/Drugs/GuidanceCompliance%20Regulatory Information/Guidances/UCM078749.pdf+Providing+clinical+evidence+of+effectiveness+for+human+and+bio&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&ie=UTF-8&access=p&oe=UTF-8. Published May 1998. Accessed June 3, 2016. 4. Kingham R, Klasa G, and Hessler K. Key regulatory guidelines for the development of biologics in the United States and Europe. Pharmaceutical Sciences Encyclopedia. 2013. http://dx.doi.org/10.1002/9780470571224.pse503. 5. US FDA. Overview of the regulatory pathway and FDA’s guidance for the development and approval of biosimilar products in the US. 2016. http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm486171.pdf. Accessed June 3, 2016. 6. US FDA. FDA overview of biosimilar products. http://fdabiosimilars.e-paga.com/course/framework. Accessed June 3, 2016. 7. US FDA. Quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm291134.pdf. Published April 2015. Accessed June 3, 2016. 8. US FDA. Clinical pharmacology data to support a demonstration of biosimilarity to a reference product. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm397017.pdf. Published May 2014. Accessed June 3, 2016. 9. US FDA. Good pharmacovigilance practices and pharmacoepidemiologic assessment. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126834.pdf. Published March 2005. Accessed June 3, 2016. 10. US FDA. Immunogenicity assessment for therapeutic protein products. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm338856.pdf. Published August 2014. Accessed June 3, 2016. 11. US FDA. Biosimilars: Questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm444661.pdf. Published April 2015. Accessed June 3, 2016.