The European Medicines Agency (EMA) has updated its guideline on the requirements for clinical and non-clinical development of biosimilar insulin products. The update expands the scope of the original document and gives additional detail on study design parameters.

Biosimilar Medicinal Products in the EU

EMA recently finalized its guideline on “similar biological medicinal products”—commonly referred to as biosimilars—which will enter into effect in April 2015. Biosimilars are products that are similar to an already authorized biological product, and can be considered equal to their reference product in terms of safety, efficacy, quality and biological activity.

Regulators have had to take a different approach to regulating biosimilars than for traditional generic drugs. Unlike chemically derived drugs, the complex biological processes involved in the production of biologicals makes them nearly impossible to exactly replicate. As such, EMA evaluates biosimilars based on a comparability assessment to their reference product.

Biosimilar Insulin Guideline

The new Guideline on non-clinical and clinical development of similar biological medicinal products containing recombinant human insulin and insulin analogues expands the scope of the previous guideline to include intermediate- and long-acting insulin preparations, and provides more detail on study design and safety study requirements.

The guideline says that in general, “safety studies should be performed with specific focus on immunogenicity … and include a reasonable number of patients with type 1 diabetes.”

However, in certain circumstances, the safety study requirement may be waived. To waive the safety study requirement a company must demonstrate similarity between the biosimilar and its reference insulin product in “the physicochemical and functional characterization and comparison … and from the comparison of the pharmacokinetic and pharmacodynamic profiles,” and ensure there are no concerns related to the impurity profile or excipients of the product.

The guideline states that biosimilarity will be measured, “based on the physicochemical and functional characterization, the pharmacokinetic and, where needed, pharmacodynamics profiles and absence of safety issues with subcutaneous use will allow extrapolation to intravenous use, if applicable, and to other indications and patient populations licensed for the reference product.”

EMA has also published the comments it received during the consultation period for the guideline.

EMA Guideline, Overview of Comments