Innovation is not always the first term that comes to mind with respect to biosimilars; after all, having no clinically relevant differences between products is at the heart of biosimilarity. However, as Sebastian Maag, device project leader for Novartis–Sandoz GmbH, told attendees during the second day of the SMi 10th Annual Biosimilars Conference, biosimilar developers have the opportunity to introduce innovations with the design of their devices for drug delivery.
Innovation is not always the first term that comes to mind with respect to biosimilars; after all, having no clinically relevant differences between products is at the heart of biosimilarity. However, as Sebastian Maag, device project leader for Novartis—Sandoz GmbH, told attendees during the second day of the SMi 10th Annual Biosimilars Conference, biosimilar developers have the opportunity to introduce innovations with the design of their devices for drug delivery.
Unlike other factors (such as price, additional data, or additional services) that differentiate biosimilars from both their reference products and from other competing biosimilars once products are already on the market, devices are a way to integrate value into the product itself, said Maag. Critically, devices can also have a significant impact on patients’ impressions of biosimilars. The device builds the relationship between the patient and the drug and can communicate quality and to the patient.
When it comes to formulation and container closure systems (CCS) for biosimilars, he said, there may be some reasons to consider mirroring the reference product rather than trying to improve upon it. First, creating a close copy of the reference drug’s formulation and CCS produces the lowest risk of changes to pharmacokinetics (PK) and stability, and apparently small differences, such as gamma-sterilization process, can impact protein stability.
Yet there also exist good reasons to innovate with regard to formulation and CCS, including the potential to allow for a more stable product with a longer shelf life, reduce injection-site pain for the patient, reduce the risk of allergic reaction by eliminating latex, or allow for fewer protein particles and impurities in the biosimilar product.
With respect to delivery devices themselves, copying the reference product’s device may require lower risk and effort during the development process, but as Maag pointed out, biosimilar developers must consider the intellectual property landscape for the innovator’s device. They should also consider the fact that reference products’ delivery devices may not represent the most up-to-date technology available, and therefore may not reflect the best patient experience possible.
Of course, the specter of meeting interchangeability guidelines for products in the United States may be a concern. For sponsors who hope to have a product designated interchangeable with its reference, questions may linger about how different a device may be from that of the innovator product while still earning the FDA’s approval as interchangeable.
While the FDA’s final guidance on demonstrating interchangeability indicates that “data and information supporting the appropriate use and performance testing of the delivery device constituent part of the proposed interchangeable product should be submitted,” in its 2017 draft guidance, the FDA indicated it would be appropriate to conduct a threshold analysis to identify differences in design between the biosimilar and its reference. In the likely case of some differences, developers were encouraged to evaluate the differences to see if they could impact appropriate use; comparative use human factor studies were also listed as potentially necessary to assess differences in use error rate. This guidance, said Maag, is challenging to implement, and the level of difficulty increases alongside the complexity of the delivery device.
While interchangeable products could, once approved, have certain commercial benefits, there are also arguable benefits to taking a purely innovative approach to device design. Maag pointed to a 2018 study of European patients’ and nurses’ preferences with respect to autoinjector devices as one example of this fact.1 The study revealed that patients felt that ease of performing self-injection, ease of grip, and a convenient start to the injection process were extremely important, and in a forced-choice question, 89% of patients said they would recommend a biosimilar’s autoinjector device to other patients over the innovator’s device after having used both options.
This study highlights the opportunities to improve patient experience, suggested Maag, who also alluded to other opportunities to enhance product designs. Reusables could potentially lower costs and provide greater sustainability, connected devices could help with patient adherence, choice of injection speed and depth could allow for greater patient convenience, dose adjustability could allow for bodyweight dosing, and customized dosing syringes could provide greater dose accuracy, he said. The often-neglected area of secondary packaging is also ripe for innovations, such as the exclusion of latex, the provision of easy-open packs, and the use of sustainable materials.
Above all, biosimilar makers should be thinking carefully about their device designs early on, said Maag, rather than close to launch. Creating a complex device to deliver a biosimilar can be “easily 5 to 10 years in the making.”
1. Tischer B, Mehl A. Patients’ and nurses preferences for autoinjectors for rheumatoid arthritis: results of a European survey. Patient Prefer Adherence. 2018;2(12):1413-1424. doi: 10.2147/PPA.S169339.