How Biosimilars Are Approved

In highly regulated markets, biosimilars will be approved based on robust data packages that demonstrate similar patient efficacy and safety profiles as reference products.

Around the world, biosimilar standards for approvals have areas of distinction. In the U.S., Europe, Japan, Canada and Australia, regulatory authorities will require developers of biosimilars to meet high quality, safety and efficacy standards. More specifically, regulators of these countries will require robust analytical (lab testing), toxicology (animal testing), and clinical data, including pharmacology (human testing) data to demonstrate “high similarity” between a biosimilar and the reference product.1 

Regulating biosimilars — importance of analytical data & totality of evidence

Since biosimilars are much more complex than small molecule generics, biosimilar manufacturers will be expected to develop robust analytical and clinical data to demonstrate that there are no significant clinical differences to a known reference product. However, since biosimilars are intended to mimic the patient effect of a known product, the clinical data requirements to demonstrate biosimilarity are more targeted than for original, innovative products. For example, Phase II data (often used to understand the right dose for patients) is not necessary in biosimilar development since appropriate dosing is already known from the reference product. On the other hand, since the clinical data package for a biosimilar is smaller than for an innovative product, the “Totality of Evidence” — including extensive analytical data — is critical to demonstrating high similarity to a reference product.  

The importance of comparative analytical data is a unique dynamic of biosimilars. The right package of analytical data that proves critical quality attributes of a biosimilar have been matched to the reference product needs to be reviewed along with the targeted clinical data package. Regulators will use the total data package to make two key decisions:

  1. Whether to approve the biosimilar for patient use in the disease indications studied with the product; 
  2. Whether to approve the biosimilar with extrapolation to the specific set of disease indications listed in the full label of the reference product, including disease indications not clinically studied for the biosimilar.

Different regulatory agencies will make different choices on both approval and biosimilarity based on interpretation of the data available for the biosimilar and the reference product. In most cases, if the product has matched all critical quality attributes and functions of the reference product through robust analytical testing, and has demonstrated no clinically meaningful differences, regulators will approve the biosimilar application with extrapolation to all uses of the reference product.

FDA Proposed ‘Totality of Evidence’ to Demonstrate Biosimilarity2

Highly Similar Analytical and Pharmacology Data Assumes Lower Risk of Clinical Differences

Global Biosimilar Guideline/Regulation Development

Global Biosimilar Guideline/Regulation Development

WHO On Biosimilars

In 2009, the World Health Organization (WHO) developed a set of globally accepted standards to assure safety, efficacy and quality of biosimilar medicines.

U.S. FDA On Biosimilars

The Biologics Price Competition and Innovation Act (BPCIA) of 2010 created a pathway for biosimilars to be approved by the FDA. Biosimilars have not yet been made available, but are expected to enter the market in 2015.

EMA On Biosimilars

The European Medicines Agency (EMA) was the first major regulatory agency to develop biosimilar guidelines (in 2005). Today, six classes of biosimilar products are available on the market.