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Biologics & Biosimilars - Joan o'callaghan - April 5th 2016


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Joan O'Callaghan of the HPRA provides the regulatory perspective for biologic and biosimilar medicines in Ireland

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Biologics & Biosimilars - Joan o'callaghan - April 5th 2016

  1. 1. Biosimilars: Regulatory Perspective in Ireland Joan O’Callaghan IPPOSI Breakfast Seminar: Biologics and Biosimilars in Ireland 5th April 2016
  2. 2. Overview • Biological medicines • Biosimilar medicines • Biosimilar approval process • Pharmacovigilance of biological medicines • Interchangeability 05/04/2016 2
  3. 3. Biological Medicines
  4. 4. What is a biological medicine? • Biological medicines contains active substances made by a biological process or are derived from a biological source. • Broad term and examples include – Hormones (e.g. insulin) – Enzymes (enzyme replacement therapy) – Monoclonal antibodies (targeted treatment) – Blood derived products (clotting factors) – Animal derived products (e.g. heparin, vaccines) 405/04/2016
  5. 5. What is a biological medicine? • Biological medicines provide effective treatments for a wide variety of serious conditions. Examples include – Diabetes mellitus (Lantus®) – Rheumatoid Arthritis (Humira®) – Cancer (Herceptin®) – Multiple Sclerosis (Tysabri®) 05/04/2016 5
  6. 6. What is a biological medicine? • Most biological medicines are produced from the cell cultures of living organisms • Often the cells have been engineered in order to produce a therapeutic molecule or group of molecules, usually proteins 05/04/2016 6
  7. 7. Biological medicines have a complex manufacturing process 05/04/2016 7 Source: Slide by Nanna Aaby Kruse, Mediacademy, Oct 2011
  8. 8. Biological Medicines and Chemical Medicines 05/04/2016 8
  9. 9. Biological Medicines and Chemical Medicines Biological medicines Chemical Medicines Large complex structure Inherent natural variability Synthesis in living organisms- difficult to reproduce No two batches likely to be identical More likely to cause an immune reaction due to size and structure Generally given by injection/infusion Generally prescribed by specialists Small simple structure Single well defined chemical structure Made by combining chemical ingredients Reproducible manufacturing process Unlikely to cause immune reaction due to small size Often taken orally Prescribed by GPs and/or specialists05/04/2016 9
  10. 10. Relative complexity of chemical and biological medicines! 05/04/2016 10
  11. 11. Biological Medicines • Biological medicines have revolutionised the treatment of many diseases including cancer, rheumatoid arthritis, psoriasis, inflammatory bowel disease and diabetes • Biological medicines are high cost and use is often limited • Patents of many ‘blockbuster’ biological medicines have expired or are nearly expired 05/04/2016 11
  12. 12. Sales and patent expiry 05/04/2016 12
  13. 13. Biosimilar medicines
  14. 14. What is a biosimilar medicine? A biosimilar is a biological medicine that is highly similar to another biological medicine (reference product) that has already been approved for use in patients A biosimilar is not a generic 05/04/2016 14
  15. 15. Biosimilars v’s Generics • Generic medicines are usually small molecule ‘chemical’ medicines • A generic medicine is an exact copy of a reference medicine • It is not possible to make an exact copy of a biological medicine 05/04/2016 15
  16. 16. Biosimilar medicines • Only comes on market after patent of reference product has expired • Encourages competition which can lead to price reductions and improve patient access to high cost medicines 05/04/2016 16 “Similar but not identical” .
  17. 17. Biosimilar medicines in Europe Active substance Reference product Biosimilars Epoetins Eprex Absamed, Epoetin Alfa Hexal, Binocrit, Retacrit, Silapo, Etanercept Enbrel Benepali Filgrastim Neupogen Filgrastim Hexal, Biograstim, Ratiograstim, Grastofil, Tevagrastim, Nivestim, Zarzio, Accofil Follitropin GONAL-f Ovaleap, Bemfola Infliximab Remicade Remsima, Inflectra Insulin glargine Lantus Absaglar Somatropin Genotropin Omnitrope 05/04/2016 17
  18. 18. Biosimilar approval process
  19. 19. Biosimilar approval process  Manufacturers must demonstrate to regulators that biosimilars have similar quality, safety and efficacy to the reference product and there are no clinically meaningful differences between the two  Tailored approach which involves a comparability exercise against the reference product  First step: quality comparability  Second step: pre-clinical comparability  Third step: clinical comparability 05/04/2016 19
  20. 20. Quality comparability • Quality testing is cornerstone of biosimilarity • Large number of physiochemical and biological tests • Quality comparability exercise must show biosimilar is highly similar to reference • Potential impact of any (minor) quality differences on safety and efficacy must be addressed 05/04/2016 20 Quality Clinical
  21. 21. Pre-clinical comparability  Pre-clinical studies are required for all new medicines. Involves testing in cell culture and in animals in order to determine safety profile prior to use in humans  For biosimilars preclinical studies relate to mechanism of action of medicine and could uncover subtle differences between reference and biosimilar  Testing in animals may not always be necessary 05/04/2016 21
  22. 22. Clinical comparability  Clinical trials are designed to see if clinically meaningful differences exist between reference and biosimilar  Generally includes data on pharamacokinetics, pharmacodynamics, safety and efficacy  Testing for immunogenicity required 05/04/2016 22
  23. 23. Indication extrapolation • Clinical data may not be required for the biosimilar in all indications • Must be scientifically justified • Similar approach is used to justify post-approval changes for other biological medicines • Approved on case by case basis 05/04/2016 23
  24. 24. Pharmacovigilance
  25. 25. Pharmacovigilance  Science of monitoring, evaluating and preventing drug-related adverse events  Clinical safety of all biologicals must be monitored on an on-going basis after approval  New medicines including biosimilars are subject to additional monitoring for a certain time period after authorisation  Patients should report side effects to the HPRA and/or their healthcare professional 05/04/2016 25
  26. 26. Traceability of biological medicines 05/04/2016 26 Biological medicines exhibit variability: therefore biological medicines with the same international non-proprietary name (INN) should not be considered identical Prescribe, dispense and record using brand name Changes in manufacturing processes can affect likelihood of medicine causing an immune reaction Adverse reaction reports should include brand name and batch number
  27. 27. Information for patients on the approval process of a medicine
  28. 28. Information for patients European Medicines Agency website: ‘Find Medicine’ section • Summary of assessment available • Further information: Package leaflet etc. 05/04/2016 28
  29. 29. HPRA Guideline on biosimilars • Regulation • Product information • Prescribing • Dispensing • Traceability 05/04/2016 29
  30. 30. Interchangeability
  31. 31. 3105/04/2016 Interchangeability, substitution and switching  Interchangeability: medical practice of changing one medicine for another that is expected to achieve the same clinical effect in a given clinical setting and in any patient (prescriber is involved)  Substitution : practice of dispensing one medicine instead of another equivalent and interchangeable medicine at the pharmacy level without consulting the prescriber  Switching: decision from treating physician to exchange one medicine for another medicine with the same therapeutic intent in patients who are undergoing treatment.
  32. 32. Substitution in Ireland • ‘Generic substitution’ allows for most chemical medicines to be substituted for each other at the pharmacy level • Biological medicines are excluded from ‘generic substitution’ • Pharmacists cannot ‘substitute’ a reference medicine for a biosimilar or vice versa unless there is prescriber agreement 05/04/2016 32
  33. 33. HPRA position on interchangeability and switching 05/04/2016 33 If it is planned to change the medicine a patient receives from a reference to a biosimilar medicine or vice versa, the treating physician should be involved; this should involve discussion between the prescriber/patient and prescriber/dispensing pharmacist • Ongoing engagement between prescribers, dispensers and those with responsibility for procurement • Stakeholder engagement to ensure optimal use of resources and ensure the best patient outcomes • Switching back and forth not recommended as currently availability of data on the impact of this is limited
  34. 34. International policies • Tendering process determines which brand of biological medicine is used in hospitals • High uptake of infliximab biosimilar (new patients and switching) Denmark • Pharmacist substitution possible if brand is given an ‘a’ flag following evaluation by the reimbursement body • Prescriber and patients retain right to decline substitution Australia • Category for ‘interchangeable biological product’ (no medicine approved in this category to date) • Legislation to allow pharmacist substitution of ‘interchangeable biological products’ passed in 16 states United States 05/04/2016 34
  35. 35. Regulatory Science Ireland: Biosimilars Research Project
  36. 36. Regulatory Science Ireland 05/04/2016 36
  37. 37. RSI: Biosimilar Project • Research activities: HPRA and UCC • Supported by: HPRA, UCC and IPHA • Industry Advisors: Merck, AbbVie, Novartis • Objectives • Peer reviewed scientific publications (practical considerations for healthcare professionals) • Survey perspectives and understanding of biosimilars • Comparative studies of international models for providing safe and effective use of biosimilars • Develop training materials and online resources • Outreach activities 05/04/2016 37
  38. 38. RSI Biosimilar Project Publications to date • Biosimilar Medicines: Opportunities and Challenges in the clinical use and supply of Biosimilars (IPN and HPN) • Biosimilar Medicines: Recent Developments (HPN) Prescriber survey • Knowledge, behaviours and attitudes towards biological medicines specifically biosimilars 05/04/2016 38
  39. 39. Any questions?