biologics & biosimilars - joan o'callaghan - april 5th 2016
TRANSCRIPT
Biosimilars: Regulatory Perspective in IrelandJoan O’Callaghan
IPPOSI Breakfast Seminar: Biologics and Biosimilars in Ireland5th April 2016
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Overview • Biological medicines• Biosimilar medicines• Biosimilar approval process• Pharmacovigilance of biological
medicines• Interchangeability
Biological Medicines
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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)
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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®)
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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
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Biological medicines have a complex manufacturing process
Source: Slide by Nanna Aaby Kruse, Mediacademy, Oct 2011
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Biological Medicines and Chemical Medicines
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Biological Medicines and Chemical Medicines
Biological medicines Chemical MedicinesLarge 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 specialists
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Relative complexity of chemical and biological medicines!
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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
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Sales and patent expiry
Biosimilar medicines
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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
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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
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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
“Similar but not identical”
.
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Biosimilar medicines in EuropeActive substance
Reference product
Biosimilars
Epoetins Eprex Absamed, Epoetin Alfa Hexal, Binocrit, Retacrit, Silapo,
Etanercept Enbrel BenepaliFilgrastim Neupogen Filgrastim Hexal,
Biograstim, Ratiograstim, Grastofil, Tevagrastim, Nivestim, Zarzio, Accofil
Follitropin GONAL-f Ovaleap, BemfolaInfliximab Remicade Remsima, InflectraInsulin glargine
Lantus Absaglar
Somatropin Genotropin Omnitrope
Biosimilar approval process
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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
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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
Quality
Clinical
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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
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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
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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
Pharmacovigilance
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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
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Traceability of biological medicines
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
Information for patients on the approval process of a medicine
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Information for patientsEuropean Medicines Agency website: ‘Find Medicine’ section• Summary of assessment
available• Further information: Package
leaflet etc.
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HPRA Guideline on biosimilars
• Regulation• Product information• Prescribing• Dispensing• Traceability
Interchangeability
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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.
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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
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HPRA position on interchangeability and switching 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
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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
Regulatory Science Ireland: Biosimilars Research Project
Regulatory Science Ireland
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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
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RSI Biosimilar ProjectPublications 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
Any questions?