Transcript Document

Marcel H.N. Hoefnagel
2 November 2007
BIOSIMILARS are not Generics
But similar
Content
• Generics and Biosimilars
• Review for Marketing Authorisation
• Efficacy and Safety
• Pharmacovigilance
• Conclusion
The content of this presentation is the view of the authors and does not
necessarily represent the opinion of the Dutch MEB and/or EMeA/CHMP
2/13
Generics
• “A generic drug is a copy that is the same as a
brand-name drug in dosage, safety, strength, how it
is taken, quality, performance and intended use”
• “before approving a generic drug product, FDA
requires many rigorous tests and procedures to
assure that the generic drug can be substituted for
the brand name drug.”
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Generics FAQ
• Are generic drugs as safe as brand-name drugs?
Yes. FDA requires that all drugs be safe and effective. Since generics
use the same active ingredients and are shown to work the same way
in the body, they have the same risks and benefits as their brandname counterparts.
• Are generic drugs as strong as brand-name drugs?
Yes. FDA requires generic drugs to have the same quality, strength,
purity and stability as brand-name drugs.
• Do generic drugs take longer to work in the body?
No. Generic drugs work in the same way and in the same amount of
time as brand-name drugs.
• Are brand-name drugs made in more modern facilities than
generic drugs?
No. Both brand-name and generic drug facilities must meet the same
standards of good manufacturing practices.
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Biosimilars are not generics
• Biological medicines produced in a
living system or organism
• The (complex) manufacturing
process is a determining factor
• Larger molecules, complex (three-dimensional structure )
and heterogeneous (e.g. isoforms and multimers)
• Difficult to characterise
• Impurities: Both Product-related and Process-related
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Biosimilar Market Application
• Comparability (quality, non-clinical, clinical)
• EU registered reference product
• Same pharmaceutical form, strength,
administration route
• Abbreviated application; Differences
supported by additional data
• Generally same indication(s) as reference
product
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Biosimilar: Stepwise approach
• Case-by Case
• Qualitative Comparability
• Non-clinical
- Toxicity studies
• Clinical studies
- Pharmacokinetics
- Pharmacodynamic studies
- Efficacy studies
- Immunogenicity
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Comparability exercise
• Complete Module 3 (Quality dossier)
• Plus Comparability Excercise
- After process change or Biosimilar
• Reference product
• Identical primary structure (AA order)
• Post-translational differences (incl. glycosylation)
• E.g. Non-PEGylated vs. PEGylated not accepted
• Physicochemical characterisation
• Biological activity
• Impurities
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Non-clinical studies
• Case-by-Case dependent on physicochemical and
biological characterisation (e.g. different glycosylation or
impurities)
• Pharmacodynamic studies
• Toxicity studies
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Clinical studies
• Pharmacokinetics
- Phase I safety
- Clinical comparability with reference product
• Pharmacodynamic studies
• Phase III Comparability
- Similar efficacy
• pharmacodynamic markers
- Similar or lower Adverse Events Incidence
- Immunogenicity
• with or without clinical consequences
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Immunogenicity and Pharmacovigilance
• Immunogenicity an issue for all biologicals (both innovators
and biosimilars)
• Immunogenicity also after process change!!
• Minimum of 12 months data available; 24 months ongoing
study post-approval
• Minimise unnecessary switching between products (also
between innovators)!
• Pharmacovigilance: Traceability important
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Conclusion
• Demonstrated Efficacy & Safety
• Quality ensured
• Pharmacovigilance: Traceability important
- be perceptive for unexpected effects on both safety and efficacy of
all biologicals
• Minimise unnecessary switching between products
- switching should always be done with care
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Biosimilars FAQ
• Are Biosimilars as safe as innovator drugs?
Yes. EMEA requires that all drugs be safe and effective. Since
biosimilars use the same active ingredients and are shown to work
the same way in the body, they have the same risks and benefits as
their innovator counterparts.
• Are Biosimilars drugs as strong as innovator drugs?
Yes. EMEA requires biosimilars to have the same quality, strength,
purity and stability as reference product.
• Do Biosimilars take longer to work in the body?
No. biosimilars work in the same way and in the same amount of time
as innovator drugs.
• Are innovator drugs made in more modern facilities than
Biosimilars?
No. Both innovator and biosimilars manufacturing facilities must meet
the same standards of GMP.
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