Establishing biosimilarity requires more extensive data generation than establishing comparability.2,3
A manufacturer may introduce a process change for reasons such as meeting regulatory requirements or increasing efficiency and/or reliability. When a change is made, the manufacturer will analyze through a comparability assessment the pre- and post-change product properties to demonstrate that the process change did not adversely impact the product. The amount and type of supporting data required to establish comparability varies according to the nature of the manufacturing change. In general, the data requirement will be less extensive than that required when establishing biosimilarity.
It is important to recognize that making a manufacturing process change and a comparability assessment is not the same as developing a biosimilar—developing a biosimilar is far more complex. In fact, in February 2012, the US FDA issued draft guidance for the industry titled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.” In this document, the FDA acknowledges the difficulty of demonstrating biosimilarity and clarifies the limitations of comparing this exercise with a comparability exercise after a manufacturing change.
Part of this complexity lies in the fact that the innovator product information remains proprietary and is not available to the biosimilar manufacturer. Therefore, the manufacturer begins with only the final product and must work to develop a process to produce the biosimilar. In contrast, a manufacturer conducting a comparability exercise following a manufacturing change in one of its existing products will have a “head start” as they begin with extensive knowledge and history about the product.
requirements for comparability exercises for a moderate-risk and a high-risk
manufacturing change by the same manufacturer compared with a biosimilar
||Manufacturing process changes are governed by the International Council for Harmonisation (ICH) Q5E comparability guidance: comparability of biotechnological/biological products subject to changes in their manufacturing process.