Intended Biosimilars

There have been examples where biologics were developed as intended biosimilars, but had meaningful differences and were non-comparable to reference products.

Development and manufacturing of high-quality biosimilars is complex and requires extensive scientific expertise. When high standards for demonstrating similarity and maintaining high-quality manufacturing and distribution are not met, patients can be adversely affected as has been the case with intended biosimilars, also called non-comparable biologics.

Biosimilars from different manufacturers will differ from each other and in their level of similarity to the reference product. Strict product quality testing is critical to ensure that biosimilars offer patients high-quality therapeutics to treat their diseases. Demonstrating a high level of analytical similarity between a biosimilar and its reference product is an early foundational step in the development of biosimilars — especially when, by definition, no two biologics or biosimilars are alike.

When high standards for demonstrating similarity have not been maintained, intended biosimilars, known as non-comparable biologics, have been given to patients with significant negative consequences. The use of non-comparable biologics has occurred in countries that may not be highly regulated. A non-comparable biologic is intended to function like a known biologic medicine, but has not undergone strict quality product development; when analytically tested it is found to have important differences compared to the intended reference product. Unlike biosimilars in highly regulated environments, the development of non-comparable biologics is not optimally designed around physical and biochemical characteristics of the reference product. Additionally, it may or may not have comparative safety and efficacy data against the reference product and has been approved by less established local regulatory pathways.

Why do High Regulatory and Product Quality Standards Matter?

In a study of non-comparable biologics to erythropoietin, a biologic that stimulates red blood cell production, a high incidence of pure red cell aplasia (PRCA) was demonstrated in patients in Thailand. PRCA, a potentially deadly disease in which red blood cell development stops, was shown to be 14 times higher in Thailand than the average observed in markets with fewer available erythropoietin products.1

 “[For the Thai population] Estimation of risk for anti-r-HuEpo-associated PRCA was calculated … 1 out of 2608 patients using biosimilar r-HuEpo would develop PRCA.” 2

Many other studies comparing a specific biologic from several less regulated countries around the world have demonstrated differences in product purity which underscores the high level of variability between biologics and forms the basis for requiring robust preclinical testing in-lab, and consistent high standards of quality control. These differences can potentially impact immunogenicity and patient safety, which is why high-quality product development and manufacturing managed by experienced scientists are critical to delivering high-quality biosimilars to patients.

Biosimilars offer patients a range of therapeutic options. In markets with high regulatory standards, biosimilars will be required to show rigorous analytical and stepwise clinical data to demonstrate similarity to the reference product.

Studies comparing biologic samples from less regulated markets:

The U.S. Food and Drug Administration (FDA)

“Health care professionals and consumers can be assured that FDA will require licensed biosimilar and interchangeable biological products to meet the Agency’s exacting standards of safety and efficacy.”