Industry has called for US Food and Drug Administration (FDA) guidance on biosimilars since Congress created an abbreviated approval pathway in 2010. The wait is now over. In three documents the FDA has laid out its thinking on biosimilars, including the use of alternative drug delivery devices.
“Some design differences in the delivery device or container closure system used with the proposed biosimilar product may be acceptable”, the FDA wrote in one of three biosimilar draft guidance question and answer documents it released.
If a company gives the FDA adequate data it can package its biosimilar in a pre-filled syringe or auto-injector device, even if the reference product was sold in vials. Using an alternative device could allow biosimilar developers to gain an edge over innovators by improving compliance.
The challenge will be convincing the FDA to approve the change. Companies must show that the new device or closure system is compatible with the biosimilar formulation by running studies on stability, leachables and other factors. Biosimilars must have the sameroute of administration as references.
Applications must also consider whether the delivery device will limit ability to switch between a biosimilar and its reference product. The FDA will look at whether the device necessitates added instruction to patients or healthcare providers, as well as changes to other factors, such as design attributes.
If the changes are too significant the FDA will reject applications. Any device that creates a ‘clinically meaningful difference’ between the safety, purity, and potency of a biosimilar and its reference will be rejected.
Additional work may be needed to support some applications. “A proposed biosimilar product in a delivery device will be considered a combination product and may, in some instances, require a separate application for the device”, the FDA wrote.
Differences between the formulation of a biosimilar and its reference may also be acceptable. Again, it comes down to data. Applicants must show that the biosimilar is ‘highly similar’ even if there are minor differences in its use of excipients.
“It may be possible, for example, for a proposed product formulated without human serum albumin to demonstrate biosimilarity to a reference product formulated with human serum albumin”, the FDA wrote.
Requirements for active ingredients are tighter. In general, biosimilars must have the same amount and concentration of drug substance as reference products, but for some complex biologics ‘a modified approach may be needed’.