Panama City, Panama April, 12-15, Marcelo Mario Matos Moreira. The Brazilian Health Surveillance Agency (ANVISA)

Transcription

1 DIA Latin American Regulatory Conference Panama City, Panama April, 12-15, 2011 Biosimilars/Biotechnology Marcelo Mario Matos Moreira Coordinator Office of Biological Products The Brazilian Health Surveillance Agency (ANVISA) Agência Nacional de Vigilância Sanitária

2 The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved., DIA and DIA logo are registered trademarks or trademarks of Inc. All other trademarks are the property of their respective owners. 2

3 What do we mean by biological/ biotechnology products? Biotechnology products include complex molecules produced using living organisms for therapeutic use. Biotech drug Small molecule drug 3

4 What is a Biosimilar or Follow-on Biologic? A Biosimilar medicinal product is a successor to a biological medicinal product for which patent protection no longer applies Manufactured by recombinant DNA technology (insertion of gene into the host cell to produce the protein) 4

5 What is a Biosimilar or Follow-on Biologic? Comparable with the selected reference product (the already licensed biological medicinal product) in terms of quality, safety and efficacy The Biosimilar product can be approved for the same indications as thereference product given that they share the same mode of actions 5

6 Different names for the same product BIOSIMILAR SIMILAR BIOTHERAPEUTIC PRODUCTS BIOSIMILAR Generic Biological Biogenerics FOLLOW ON BIOLOGICS (FOB) MEDICAMENTO BIOLÓGICO SIMILAR (BIOSIMILAR) BIOLOGICAL PRODUCT FOLLOW-ON PROTEIN SUBSEQUENT ENTRY BIOLOGICS PRODUCT (FOPPs) FOLLOW ON BIOLOGICS (FOB) 6

7 A biosimilar is not a generic - Biosimilars usually do not meet all the conditions to be considered d as a generic product mainly due to manufacturing process characteristics raw materials used molecular characteristics therapeutic modes of action 7

8 Biosimilar development - The development of a Biosimilar medicine requires a complete product and process development PLUS a comparative testing at all stages of development in order to obtain approval by competent authorities Reference product Comparative Comparative Target Complete Characterization Physicochemical and Biological Comparability Comparative Preclinical Studies Comparative Clinical Studies Risk Management Plan Biopharmaceuticals approved as biosimilar medicines 8

9 Quality - Elucidation of structure and other characteristics primary and higher-order structure post-translational modifications biological activity purity impurities product-related substances immunochemical i properties 9

10 Quality - Comparability of a product claimed to be similar to another biological product already marketed cannot be made on gross physico-chemical and biochemical i aspects alone. Pre-clinical and clinical studies will be necessary. 10

11 Quality - Key points to be considered: Characterisation studies Manufacturing process Stability data 11

12 Quality - The manufacturer will not have access to all the information that would allow comparison in terms of quality of the marketed product: Expression/vector system Production and purification details Analytical techniques 12

13 Quality - General principles: Address pharmaco-toxicological assessment of the Biosimilari il Should be conducted with the final formulation intended for clinical use Minimum: head-to-head comparative toxicology studies Additional Non-Clinical i l data dependd of the specificities of a product 13

14 Non-clinical Evaluation - In vitro studies Methodology: Receptor-binding studies, cellbased assays, etc Purpose: establish comparability of Biological/ i l/ Pharmacodynamic activity of the Biosimilar and Reference 14

15 Non-clinical Evaluation - In vitro studies General principles Comparative in nature Performed in relevant species Employ state of the art technology 15

16 Non-clinical Evaluation In vivo studies - Endpoints Biological/pharmacodynamic activity relevant to the clinical application Non-clinical toxicity as determined in at least one repeat dose toxicity study in a relevant species and including toxicokinetic measurements 16

17 Clinical Evaluation Designed to demonstrate comparable safety and efficacy of the Biosimilar to the Reference Clinical comparability exercise: stepwise procedure; PK and PD studies followed by the pivotal clinical trials 17

18 Clinical Evaluation - Efficacy studies No dose-finding studies Demonstrate t in adequately powered, randomized, and parallel group clinical trial Equivalence or non-inferiority studies may be acceptable for the comparison of efficacy and safety of the Biosimilar to the Reference; equivalence/non-inferiorityinferiority margins have to be pre-specified and justified 18

19 Clinical Evaluation - Safety Usually, safety data obtained from the efficacy trials will be sufficient Comparison with the Reference should include type, frequency and severity of Adverse Events 19

20 Pharmacovigilance Close monitoring of the clinical safety: focus on (rare) serious Adverse Events in all approved indications Pharmacovigilance plan should describe planned activities and methods based on the safety specification Risk minimization measures may enhance safe use of Biosimilar 20

21 Implementation in Brazil RDC 55/2010 current normative landmark Route of development by comparability The regulatory route that can be used by a biological product to obtain registration from the regulatory authority, in which the exercise of comparability in terms of quality, efficacy and safety was used, between the developed d product to be comparable and the comparer biological product. 21

22 Further information and contact The Brazilian Health and Surveillance Agency Agência Nacional de Vigilância Sanitária ANVISA gov br Thank you! Muchas Gracias! 22