Biosimilars.pptx

Biosimilars

1. BIOSIMILARS DR. SARITA SHARMA ASSOCIATE PROFESSOR MMCP, MMDU

2. Biological products These are the medicines typically derived from living systems (protein or pieces of protein) and produced using biotechnological tools Unlike other drugs biological drugs must be made in living systems like ; Yeast , Bacteria or animal cells . Biologics include ; blood, vaccines ,blood components and recombinant therapeutic proteins . Biologics are very specific , highly effective medicines that improve health outcomes in many complex conditions such as ; Crohns disease ,Ulcerative colitis , diabetes , rheumatoid arthritis , cancer, HIV, osteoporosis, growth deficiencies and many . 10/20/2023 2

3. Biosimilars Biosimilars are the drugs or medicines that are similar ( close in structure and function ) to biological drugs . Biosimilars are the drugs that are similar to innovator biologic , but not identical. Biosimilars are officially approved versions of original innovator product and can be manufactured when the original products patent expires . They are similar in terms of quality , safety and efficacy to the already licensed , well established reference medicinal product . Because of structural and manufacturing complexities, these biological products are considered as similar but not generic equivalents of innovator biopharmaceutical 10/20/2023 3

4. Definition Of Biosimilars By Different Authorities As per EMA , A biosimilar medicine is a biological medicine that is similar to another biological medicine that has been already authorized for use . As per WHO , A biotherapeutic product which is similar in terms of quality , safety and efficacy to an already licensed reference biotherapeutic product . They are termed as ‘ similar biologic products . (SBP) As per US- FDA , A biopharmaceutical product highly similar to the reference product without meaningful differences in safety , purity and potency . They are termed as Follow on Biologics , (FOB) As per HEALTH CANADA , Drugs that enters market subsequent to a version previously authorized in Canada with demonstrated similarity to a reference biologic drugs . They are termed as Subsequent Entry biologics . (SEB) 10/20/2023 4

5. History First approved in Europe by EMEA -2006 (Omnitrope = Genotropin) In US by FDA in 2015 – ZAXIRO( Filgrastim - For neutropenia) In India first biosimilar product was developed in 2000 . Category Active substance Biosimilar Uses Human growth hormone Somatotropin, Genotropin Omnitrope Growth deficiency hormone Recombinant product Epoetin Epoetin alfa HEXAL To treat anemia Monoclonal antibody Infliximab Inflectra To treat chronic inflammatory diseases Hormones Insulin Glargine Abasaglar To treat hyperglycemia 10/20/2023 5

6. Biosimilar Vs Original Innovator Biologic 10/20/2023 6 Biosimilars are not exact copies of originator biologic and neither these are expected to be the exact replicas of innovator biologics as the manufacturing process through which the biologic is made cannot be exactly duplicated by another manufacture . Biosimilars are similar to their innovator product but there being some minor differences in the structure due to different manufacturing process involved, however these differences are not clinically significant. Thus clinical outcomes of innovator biologics and biosimilars are identical. Though both innovator biologic and Biosimilars being protein in nature have immunogenic potential, biosimilars tend to produce more adverse drug reactions than reference product.

7. Biosimilar Vs Original Innovator Biologic 10/20/2023 7

8. Difference Between Biosimilars And Generics Biosimilars Generics Produced by living cell cultures Produced by chemical synthesis High molecular weight compounds Low molecular weight compounds Complex dimensional structure Well defined structure Unstable and sensitive to external conditions Stable immunogenic Mostly non immunogenic Clinically identical to their reference products but not the same (active product likely to have variations) Therapeutically equivalent with their reference products (active product is always same) Manufacturing is complex and variable Manufacturing is simple and consistent 10/20/2023 8

9. Difference Between Biosimilars And Generics Biosimilars Generics For approval regulators require clinical trials, manufacturing and post-approval safety monitoring programs similar to that of the original innovator companies . For approval regulators require bioavailability and bioequivalence studies . 10/20/2023 9

10. Comparison Of Biologic Biosimilar And Generic Process Biologic Biosimilar Generic Manufacturing Produced by biological process in host cells. Sensitive to production changes-Expensive and specialized production facilities. Reproducibility difficult to establish. Produced by biological process in host cells. Sensitive to production changes-Expensive and specialized production facilities. Reproducibility difficult to establish. Produced by using chemical synthesis. Less sensitive to production changes. Reproducibility easy to establish. 10/20/2023 10

11. Comparison Of Biologic Biosimilar And Generic Process Biologic Biosimilar Generic Clinical development Extensive clinical studies , including phase I—III. Pharmacovigilance and periodic safety updates needed. Extensive clinical studies , including phase I—III Pharmacovigilance and periodic safety updates needed. Often only phase I studies. Short timeline for approval. Regulation Needs to demonstrate , comparability regulatory pathway defined by Europe (EMEA) Currently no automatic substitution intended. Needs to demonstrate , similarity regulatory pathway defined by Europe (EMEA) Currently no automatic substitution intended. Needs to show, bioequivalence abbreviated registration procedures in Europe and US Automatic substitution allowed. 10/20/2023 11

12. Manufacturing Of Biosimilars Once the patent for the original biologic expires ,It is legal for other manufacturers to create a biosimilar. As the company of the original biologics is not obliged to share its manufacturing process , the biosimilar manufacturers need to start from scratch . The different steps involved in manufacture of biosimilars are : STEP 1:- First biosimilar manufacturers need to analyze the original biologic band go through published data in order to reproduce the basic structure of the biologic. 10/20/2023 12

13. Manufacturing Of Biosimilars STEP 2 :- Next they need to replicate the three dimensional drug with the functional or what we called as the clinically active parts . This is very complicated process . Scientists need to depend on cultures of living cells to assemble the drugs . 10/20/2023 13

14. Manufacturing Of Biosimilars 10/20/2023 14

15. Manufacturing Of Biosimilars STEP 3 :- Once it has been made the new drug (biosimilar)needs to undergo rigorous evaluations to make sure that its chemistry and function are similar to the original biologics . The new drug (biosimilar) also need to undergo functional test to make sure that it can bind to its target, just as its original biologics. STEP 4 :- The new drug needs to be compared to the original biologics in clinical trials to make sure it works just as well as the original biologic and does not set off any unexpected effects in the body . Biosimilar manufacturers need to meet rigorous standards in terms of safety , purity and potency . This whole process can take more than 10 years. 10/20/2023 15

16. Regulatory Guidelines For Approval Of Biosimilars In India regulatory requirements for marketing authorization of biosimilars were released in 2012. The data requirement includes :- Analytical and Quality characterization Data : Comparability according to critical attributes of product including physicochemical properties , biological activity, immunological properties , functional assays , purity etc. Non clinical studies : In vitro studies . E.g , cell based bioassay (cell proliferation assays or receptor binding assays). In vivo studies : PD activity , immunogenicity, toxicity study , safety, mutagenicity, reproductive toxicity and carcinogenicity studies. 10/20/2023 16

17. Regulatory Guidelines For Approval Of Biosimilars C linical studies : Phase I : comparative PK and PD studies, PK\PD relationship may be evaluated. PD evaluation can also be done as part of phase III study . Phase II: dose ranging studies . Phase III : comparative efficacy and safety\immunogenicity study. Equivalence design ,study is preferred. Phase IV : Post marketing , safety and immunogenicity data must be submitted. Comparative clinical studies : Mechanism of action . Route of administration (dosage form and strength in comparison to licensed reference product 10/20/2023 17

18. Regulatory Guidelines For Approval Of Biosimilars 10/20/2023 18

19. Issues Related To Biosimilars Efficacy issues : issue arising from difference between the bioactivity of biosimilar and their innovator product. E.g ; Epoetin alpha products. 11 Epoetin from 4 different countries ( Korea , Argentina , China , India ) were analyzed and significant diversions from specifications for in vitro activity were observed. Deviations varied in range from 71 to 226%. 10/20/2023 19

20. Issues Related To Biosimilars Safety issues : These are the concerns regarding immunogenicity . The immune response , also called as immunogenicity . Since biologics are proteins, the body can develop antibodies to them over time , which might effect their activity . E.g , Eprex . Eprex is a biosimilar of Epoetin alpha produced outside the US. Change in the manufacturing process by replacing Human albumin stabilizer by polysorbate 80 resulted in increased immunogenicity. 10/20/2023 20

21. Issues Related To Biosimilars Substitution : Prescribed chemical entity can be substituted by Generic chemical. Same rule of substitution cannot be applied in case of biosimilars due to the issues related to safety and efficacy. Uncontrolled substitution of biologics can lead to severe consequences. 10/20/2023 21

22. Benefits Of Biosimilars Effective targeted therapy is used earlier in the disease . More patients have access to treatment . Biosimilars free up budget to innovative medicines .(low costs) More treatment options . More competition in the health care market. 10/20/2023 22

23. Conclusion Biosimilars are not generic versions of originator biologics, but they are affordable alternatives that work similarly . For patients who have not begun as original biologic biosimilars may be useful alternative for physicians to prescribe . However, only qualified health care professionals should be allowed to switch a patient from an innovator biologic to a biosimilar and only if its not best for patients health . 10/20/2023 23

24. 10/20/2023 24 This Photo by Unknown Author is licensed under CC BY