Table 1.

Paradigm shift steps with regard to biosimilars.

Paradigm Shift Step	Application Descriptor
What is the current paradigm?	A biosimilar product is developed using a step-by-step plan starting with an analytical assessment, followed by animal, clinical pharmacology, and efficacy testing (Figure 1).
Define the crisis	The cost of developing biosimilars is 100 to 300 million USD each, which is too expensive for many companies.
Confirm the crisis	The 130+ biosimilars approved in the EU and US represent only 14 molecules in the EU and 9 in the US out of more than 200+ available options; the cost of approved biosimilars is still too high.
Search for solutions	The regulatory guidelines were examined for rationality, and several redundancies were discovered.
Collect solutions	Waive animal, clinical pharmacology, and efficacy testing.
Validate solutions	Thousands of studies demonstrate that no biosimilar has failed when it is analytically similar to its reference product.
Apply solutions	Educate regulatory agencies and developers to adopt a scientific rationale for studies conducted based on analytical assessments alone.
Confirm crisis resolution	While some agencies have begun revising their guidelines, such as the MHRA, and others allow waivers upon asking, the need for precise directions from agencies remains unfulfilled.
The new paradigm	When in place, biosimilars will be approved if they demonstrate analytical similarity with their reference products within the range of testing variability. Otherwise, they will be rejected as biosimilars and will be allowed to be resubmitted as new drugs.