Marcel H.N. Hoefnagel 2 November 2007

BIOSIMILARS are not Generics

But similar

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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

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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 brand-name 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.