EMA Remains Firm on PK Studies for Insulin Biosimilars

The European Medicines Agency has rejected calls from industry to use biosimilar reference products from outside the EU unless they are justified using pharmacokinetic tests.

In comments on the agency’s guideline on nonclinical and clinical development of biosimilars containing recombinant human insulin and insulin analogs, generics maker Wockhardt asked that sponsors be able to substitute in vitro chemistry, manufacturing and control comparisons. The problem with that, the EMA says, is that differences in formulations of products in the European Economic Area and those produced elsewhere may require PK comparisons.

The final guideline, released in March, recommends that sponsors use a specific type of PK test — a cross-over, double-blind hyperinsulinemic-euglycemic clamp study with single subcutaneous doses of the test and reference agents that will show that the reference and proposed insulin products are biologically similar.

Clamp studies are also sufficient to evaluate responses to single-dose and multiple-dose products, the EMA says in response to the European Biopharmaceutical Enterprises’ request to separate these studies for long-acting insulin products.

The EMA also rejected suggestions that extra studies be required to clarify individual responses to insulin and that sponsors be made to run special analyses on higher-than-therapeutic doses, saying the replicate studies mentioned in the guideline should satisfy this concern.

The agency did accept a number of industry suggestions, including several covering comparative pharmacokinetic and pharmacodynamic assessments for biosimilars and their reference products and assessments of cancer-causing properties.

An overview of the comments is available at www.fdanews.com/04-08-15-EMAcomments.pdf. — Lena Freund