The guidance released Wednesday builds largely off of three documents from the EMA (European Medicines Agency) that focus on the comparability of biologics and biosimilars, specifically those that use proteins as their active substances.
The TGA says the purpose of the guidance is to help sponsors to identify the data necessary to support the registration of biosimilars and to clarify the scientific and regulatory principles used by the TGA to evaluate those applications.
Guidance for Manufacturing
Biosimilar manufacturers have to provide evidence that they have established an in-house primary reference standard comparable to the reference biologic in the comparability study, the TGA says.
Following any significant manufacturing process changes, sponsors also must provide evidence that the new product is comparable to both the in-house primary reference standard and the pre-variation product.
But for the later stages of development, the TGA says it’s “undesirable to change the manufacturing process.” And if a significant change must be made between a clinical trial and commercial launch, the TGA requires the sponsor to include the reference product in the second comparability study to show the clinical trial and commercial products are similar.
The use of more than two comparability studies “is not acceptable as it is not possible to make robust comparison between the reference product and batches of biosimilar material made using different or evolving processes,” the TGA adds.
If direct comparisons cannot be made, for instance if the concentration of the active substance is too low in the reference product or there are interfering excipients, such as human serum albumin, then the TGA says “extraction or concentration techniques may be used” but they must be thoroughly described.
And although most biosimilars likely contain biotechnology-derived proteins as the active substances, this guidance also applies to other biosimilars consisting of vaccines and monoclonal antibodies, as well as polysaccharides, such as low molecular weight heparins.