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Generics, chemisimilars and biosimilars: is clinical testing fit for purpose?
1Medicines Assessment Ltd, London, UK. info@medicinesassessment.com
British Journal of Clinical Pharmacology
|May 12, 2012
Summary
Generic drugs ensure safety and effectiveness through bioequivalence testing. However, biosimilars and chemisimilars require advanced methods beyond simple pharmacokinetic comparisons due to dose-insensitive clinical trials.
Area of Science:
- Pharmaceutical Science
- Drug Development
- Regulatory Science
Background:
- Generic drugs rely on physicochemical control and bioequivalence criteria for safety and efficacy.
- Modern drug assays enable pharmacokinetic comparisons, demonstrating assay sensitivity for dose differences.
- Large biological molecules (biosimilars) and complex chemical products (chemisimilars) pose validation challenges.
Purpose of the Study:
- To evaluate the limitations of current validation methods for biosimilars and chemisimilars.
- To highlight the inadequacy of dose-insensitive clinical trials in assessing product equivalence.
- To advocate for the adoption of assay-sensitive equivalence tests.
Main Methods:
- Review of existing bioequivalence testing methodologies for generics, biosimilars, and chemisimilars.
- Analysis of pharmacokinetic and pharmacodynamic data correlation with dosage.
- Assessment of clinical trial outcome measures for sensitivity to dose variations.
Main Results:
- Pharmacokinetic comparisons are effective for dose-dependent drugs but insufficient for biosimilars and chemisimilars.
- Many clinical outcome measures for biosimilars and chemisimilars are insensitive to significant dose differences.
- Current testing may fail to detect clinically relevant differences between test and reference products.
Conclusions:
- A three-stage assessment (quality, lab, clinical) is used for biosimilars and chemisimilars.
- There is a critical need for dose-sensitive testing methods for these complex products.
- Advancements in pharmacokinetic and pharmacodynamic technologies will drive the shift towards assay-sensitive equivalence tests.
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