Biosimilars: controversies as illustrated by rhGH.

Area of Science:

• Biopharmaceutical Science
• Regulatory Affairs
• Pharmacoeconomics

Background:

• Biosimilars are highly similar biological medicinal products to existing reference biopharmaceuticals.
• The comparability and interchangeability of biosimilars with their reference products remain subjects of scientific and regulatory discussion.
• Recombinant human growth hormone (rhGH) biosimilars serve as a case study for these ongoing controversies.

Purpose of the Study:

• To review the controversies surrounding the regulatory approval criteria for biosimilars.
• To examine the specific concerns related to recombinant human growth hormone (rhGH) biosimilars.
• To discuss the implications for clinical practice and physician decision-making.

Main Methods:

• Literature search of MEDLINE using specific keywords and subject headings for biosimilar and rhGH regulatory approval.
• Consultation of websites from the European Medicines Agency (EMA) and the American Food and Drug Administration (FDA).
• Analysis of regulatory requirements for biosimilar approval, focusing on comparability studies.

Main Results:

• Regulatory approval by EMA requires demonstration of comparability in quality, efficacy, and tolerability.
• Certain non-clinical studies (pharmacokinetics, safety pharmacology, toxicology) are not mandatory for biosimilar approval.
• Efficacy and tolerability may be established through limited studies, with extrapolation to other indications, leading to unproven long-term data for all indications.

Conclusions:

• The current criteria for biosimilar comparability and interchangeability require further validation.
• There is a need for long-term clinical investigations and systematic monitoring of rhGH biosimilars across all indications.
• The medico-economic environment should support physicians in making informed prescribing decisions regarding rhGH products.