Extrapolation of indications for biosimilars Regulatory perspective Dr Michael Coory Director, Prescription Medicines Clinical Unit 5 Medicines Authorisation Branch Market Authorisation Division, TGA ARCS Scientific Congress 2015 7 May 2015
Regulation of medicines is international • European Medicines Agency (EMA) • United States Food and Drug Administration (FDA) • Health Canada 1 Extrapolation of indications for biosimilars
What is a biosimilar? • Biological medicine that is developed to be ‘similar’ to an existing biological medicine (the ‘reference medicine’) • It is not identical to the reference medicine. – the biological medicine is the process (“brewed” in living cells; complex processes) – Biological medicines can never be reproduced as identical molecules – The concept of identity does not apply 2 Extrapolation of indications for biosimilars
What is a biological medicine? • Medicine produced or extracted from a biological source 3 Extrapolation of indications for biosimilars
Not all biosimilars are the same • Vaccines • Blood products • Enzymes • Hormones • Immunomodulators • mAb 4 Extrapolation of indications for biosimilars
Biosimilarity is a matter of degree • Different batches of the originator product – biosimilars of the version of the product used in the pre-marketing trials – biosimilars of other batches – ‘drift’ • Some variation must be accepted for all biological medicines • The claim is similarity in all important aspects 5 Extrapolation of indications for biosimilars
Regulatory balance Avoid allowing drugs Avoid regulatory hurdles that are not adequately that are unnecessarily tested from coming to burdensome and do not market protect the public’s health 6 Extrapolation of indications for biosimilars
Costs of development Indicative Small-molecule $1 – 2M 1 – 3 years generics Biosimilars $10 – 40M 6 – 9 years New biological $B+ 10+ years medicine 7 Extrapolation of indications for biosimilars
CTD Modules • Longer process to develop the cell line and manufacturing process New biological Biosimilar medicine • Takes much longer to find a cell-line that will 3. Quality produce a product similar 3. Quality to the reference product • Shorter non-clinical and clinical 4. Nonclinical 4. Nonclinical • ‘Integrated comparability exercise’ 5. Clinical 5. Clinical 8 Extrapolation of indications for biosimilars
To maintain a regulatory balance • Avoid unnecessary clinical trials • Equivalence/non-inferiority – Need larger sample size that superiority study – 100’s of patients • Timely recruitment can be difficult 9 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005 Guideline on similar biological medicinal product … • In certain cases … can extrapolate indications • Justification depends on: – clinical experience – available literature data – mechanism of action – receptors • Also need to consider safety in subpopulations 10 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005/ Rev.1 Guideline on similar biological medicinal product … 6. Extrapolation of efficacy and safety from one therapeutic indication to another EU July 2015 Australia Consultation with industry is due to conclude 22 May 2015 11 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005/ Rev.1 • Needs to be scientifically justified • Considered in light of the totality of data: – quality – non-clinical – clinical 12 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005/ Rev.1 It is expected that the safety and efficacy can be extrapolated: • when biosimilar comparability has been demonstrated • by thorough physico-chemical and structural analyses • as well as by in vitro functional tests • complemented with clinical data (efficacy and safety and/or PK/PD data) • in one therapeutic indication. 13 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005/ Rev.1 Additional data are required in certain situations, such as 1. The active substance of the reference product interacts with several receptors that may have a different impact in the tested and non-tested therapeutic indications 2. The active substance itself has more than one active site and the sites may have a different impact in different therapeutic indications 3. The studied therapeutic indication is not relevant for the others in terms of efficacy or safety, i.e. is not sensitive for differences in all relevant aspects of efficacy and safety 14 Extrapolation of indications for biosimilars
EMEA/CHMP/BMWP/42832/2005/ Rev.1 Immunogenicity is related to multiple factors, including: • the route of administration • dosing regimen • patient-related factors and disease-related factors (e.g. co-medication, type of disease, immune status). Thus, immunogenicity could differ among indications. Extrapolation of immunogenicity from the studied indication/route of administration to other uses of the reference product should be justified. 15 Extrapolation of indications for biosimilars
Summary • Regulatory framework is evolving • Not all biosimilars are the same • Extrapolation: case-by-case 16 Extrapolation of indications for biosimilars
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