1 BIOSIMILARS & EU REGULATION Alice DOMINIQUE - M2 AREIPS 2 Content 1 Definitions 2 Regulation in EU 3 Biosimilars in practice
3 DEFINITIONS 4 What is a biological medicine ? Biological medicine = Biologic medical product = Biological = Biologic Medicine made by or derived from a biological source (human, animal or microorganism), using biotechnology Active substance larger and more complex than chemical medicine Degree of variability Examples Vaccines:
Blood and blood products Allergenic extracts Gene therapies d Human cells and tissues used for transplantation Cellular therapies 5 What is a biosimilar ? Similar biological = biosimilar medicine A biological medicine developed to be similar to an existing biological medicine that has already been authorized for use. (Reference medicine) Active substance: essentially the same But minor differences due to their complex nature and production methods
Degree of natural variability When approved, its variability and any differences between it and its reference medicine will have been shown not to affect safety or effectiveness 6 Biosimilars Generics PROPERTIES GENERICS BIOSIMILARS SIZE Small Large
MOLECULAR WEIGHT < 500-900 Daltons 4000 to >140,000 Daltons STRUCTURE Simple and well-defined Complex with potential structural variations MANUFACTURING Predictable chemical process to make identical copy Specialized biological process to make similar
copy COMPLEXITY Easy to fully characterize Difficult to characterize due to heterogeneity APPROVAL REQUIREMENTS Quality information + Bioequivalence Full quality dossier + Comparability exercise (quality, safety, efficacy) 7 EU REGULATION
8 Regulation in EU EU = first region to have set up a legal framework Concept of biosimilar adopted in EU legislation in 2004 Directive 2001/83/EC, as amended by Directive 2003/63/EG and Directive 2004/27/EC First biosimilar medicine : approved by the EC in 2006 Marketing authorisation application: Centralised Procedure Only authorized once the period of data exclusivity has expired 9 EMA guidelines relevant for biosimilars
OVERARCHING BIOSIMILAR MEDICINES GUIDELINES General Quality Nonclinical and Clinical PRODUCT-SPECIFIC BIOSIMILAR MEDICINES GUIDELINES Recombinant human insulin and insulin analogues Somatropin GCSF Recombinant erythropoietins Low-molecular-weight heparins Interferon IFN FSH Monoclonal antibodies
10 Biosimilars authorised in EU ACTIVE SUBSTANCE BIOSIMILAR MARKETING AUTHORISATION HOLDER AUTHORISATION DATE REFERENCE MEDICINAL PRODUCT NATURE SOMATROPIN
INFLIXIMAB FOLLITROPIN ALFA INSULIN GLARGINE ETANERCEPT ENOXAPARIN SODIUM Clexane 11 How to demonstrate biosimilarity? Similarity to the reference medicinal product in terms of: quality characteristics safety biological activity efficacy based on a comprehensive comparability Similar active substance, in molecular and biological terms For example: for a protein, same amino acid sequence Same posology and route of administration Deviations from the reference product as regards strength,
pharmaceutical form, formulation, excipients or presentation require justifications Any difference should not compromise safety Intended changes to improve efficacy are not compatible with the biosimilarity approach. 12 Marketing Autorisation application dossier 13 BIOSIMILARS IN PRACTICE 14 Why do we use biosimilars? In EU, in 2014 : 7/10 of the most sold medicines
Biological costs > Chemical medicines costs Biosimilars: More cost-effective alternative Offer a major opportunity to provide greater access to affordable healthcare Difficult production methods Supply difficulties Stock-outs 15 Interchangeability Medical practice of changing one medicine for another that is equivalent, in a given clinical setting on the initiative, or with the agreement of the prescriber EMA: Decisions on interchangeability : Outside its remit No recommendations Rely on national competent authority
For questions related to switching from one biological medicine to another, patients should speak to their doctor or pharmacist 16 Interchangeability ANSM: According to the evolution of the knowledge and the continuous analysis of efficiency and safety data of biosimilars in EU, it appears that a position excluding formally any interchangeability during the treatment is no longer justified But, for security and traceability reasons its not recommended to modify the initial prescription FIMEA: Biosimilars are interchangeable with their reference products under the supervision of a health care person 17
CONCLUSION 18 Conclusion Important sub-category of biologics One the fastest growing segments of pharmaceutical industry 2014: worldwide sales US$200 billion Importance in healthcare budget Complex structure Small differences can result in a significant impact on quality, safety & efficacy Importance of legislation and harmonisation 19 20 Bibliography http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/
general/general_content_000529.jsp&mid=WC0b01ac0580533e0b Guideline on similar biological medicinal products CHMP/437/04 Rev 1, 2014 Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues, EMEA/CHMP/BMWP/42832/2005 Rev1, 2014 Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (revision 1), EMA/CHMP/BWP/247713/2012 , 2014 Biosimilar medicines handbook, 3rd edition - 2016, The Biosimilar Medicines Group tat des lieux sur les mdicaments biosimilaires, Mai 2016, ANSM http://www.amgenbiosimilars.com
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Teaching Principles of One-Way Analysis of Variance Using M&M's Candy. Todd A. SchwartzDepartment of Biostatistics, Gillings School of Global Public Healthand School of NursingUniversity of North Carolina at Chapel Hill
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