What are biosimilars?

Biosimilars are versions of drugs that are made to be identical or similar to drugs that already available on the market – also known as originators, innovators or reference medicinal products (RMPs). Due to clearer regulatory guidelines and better uptake in the industry, the biosimilar market size is set to increase considerably over the coming decade.

Biosimilar development and manufacture can begin once the market patent associated with the innovator has expired. Once this development begins and biosimilar drug material is manufactured, biosimilar testing must take place. This involves comparing the biosimilar to the innovator product across various parameters in order to prove it is similar to the innovator.

Examples of biosimilar drugs that BioPharmaSpec routinely performs testing on:

Biosimilars vs Biobetters

As discussed above, biosimilars are targeted to be identical or highly similar to drugs already on the market. Biobetters are “better” versions that the marketed product. They exhibit some superiority over a marketed drug, such as an improved formulation or structural changes that may lead to better efficacy or safety.

Biosimilar and Biobetter Development

Biosimilar development and approval relies heavily on the data obtained from the protein characterization and comparability studies that have been performed on the biosimilar and the originator. For traditional recombinant proteins, much more emphasis is placed on the clinical studies. Therefore, it is important to plan effective biosimilar comparability and characterization studies, which assess all structural, physicochemical, biophysical and functional attributes.

Biobetters are treated as new drugs by the regulators and therefore have the additional regulatory requirements over biosimilars. However, the active drug is still well known and therefore development time and costs should be lower than with a new drug. Some companies have even opted developed a biobetter to their own marketed product, in order to maintain market share and protect themselves against potential biosimilars.

Biosimilar Testing

All regulatory guidelines for biosimilars, including the FDA Draft Guidance for Industry “Development of Therapeutic Protein Biosimilars: “Comparative Analytical Assessment and Other Quality-Related Considerations” state that the biosimilar should be characterized thoroughly and shown to be comparable to an innovator molecule or reference medicinal product.

These biosimilar testing guidelines state that at least 6-10 batches of your biosimilar should be compared to at least 6-10 batches of innovator product. Any fewer batches than this and it is difficult to make any statistical claims of biosimiliarity.

Many developers will not perform comparability on all of these batches at the same time. This is usually due to limited availability of innovator batches or the manufacturing schedule of your own biosimilar product. A common way to proceed would be:

  1. 1 vs 1 study with a batch of innovator and your initial biosimilar batch
    • Assess critical structural attributes to make sure your biosimilar is indeed similar.
  2. 3 vs 3 study
    • Start to assess the variance between your biosimilar and different innovator batches across a larger number of methods/ structural attributes.
  3. Further comparability studies with increasing numbers of batches, the number depending on the variance observed and batch availability

In this way, you start to build a body of data across the structural attributes. This allows you to define where your biosimilar sits in the range of results for, say, 10 batches of innovator and state whether or not the biosimilar is indeed “similar”.

Our Approach to Testing

As part of a wide range of protein characterization services, BioPharmaSpec provides a comprehensive package of testing including biosimilarity, comparability and characterization studies to support our clients who are developing biosimilars.

BioPharmaSpec meets the requirements of regulatory guidelines though biosimilar testing (e.g. biosimilarity, comparability and characterization studies) of both the biosimilar drugs and the innovators. These studies cover the protein characterization methods suggested in various biosimilar guidelines including:


BioPharmaSpec scientists have provided data to support over 75 biosimilar development programs. Contact our scientists now to understand how we can use our protein characterization methods to accelerate the development of your molecule.