Darren Mansell, regulatory affairs manager at Owen Mumford looks at the EU and US regulatory differences when it comes to drug delivery devices.
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In Europe, a fifth of total spend on biologics (€12 billion) is already exposed to competition from biosimilars.[1] Meanwhile, in the US, just under a fifth of the biologics market (worth $211 billion dollars) is exposed to biosimilar competition, and three fifths of the market has the potential for biosimilar development.[2] Manufacturers of originator biologics are taking various measures to defend against this competition, such as reformulating drugs, making dosing improvements, or changing drug delivery devices. Similarly, biosimilar manufacturers must differentiate from other producers, to be able to secure sufficient market share.
DEVICE INNOVATION
Manufacturers can choose to differentiate through their choice of delivery device. Patients are used to brand changes for their drugs and so may not react adversely if their pharmacy changes provider, but a device that improves their experience may help to retain patients in the long-term. Ease of use tends to encourage patient adherence, and is especially important now that many treatments for chronic illnesses are administered outside of the healthcare setting and often without the support of a healthcare practitioner. However, pharmaceutical manufacturers may be concerned about the regulatory implications of making device changes for combination products.
THE EU APPROACH
Guidance from the European Medicines Agency separates the drug from the delivery device, which makes the approvals process easier. Moreover, the guidance makes it clear that differences in the administration device may be allowed if there is no impact on safety and efficacy.[3] Manufacturers can therefore gain a competitive advantage by improving device usability or even changing the mode of delivery. To provide a recent example, one manufacturer developed a biosimilar suitable for subcutaneous administration, for a reference biologic that is usually administered intravenously. The formulation allows for three administration options and may even improve the effectiveness of the treatment.
FDA GUIDANCE
Unlike the EU, the US FDA has a dedicated approval pathway for combination products, where both the drug and device are assessed together. The FDA’s final guidance document titled “Considerations in Demonstrating Interchangeability with a Reference Product” is not clear on the scope for device changes. At first, the document seemingly advises against submitting an interchangeable product with a different ‘presentation’ – i.e. the device component – from the approved reference product. However, the guidance then suggests that sponsors considering this option should nonetheless approach the FDA, allowing the regulator to determine whether the proposed changes could support a demonstration of interchangeability.
TAKING INITIATIVE
Despite the ambiguity in the FDA guidance, the organisation’s increased emphasis on human factors suggests that more patient-centric devices would be welcomed, and as more organisations take the initiative to engage with the FDA, it is likely to inform future advice on this issue. Biosimilar development is highlighting the opportunity to make the administration experience more positive, and the resulting improvement in patient acceptance would be beneficial for all stakeholders, from pharmaceutical businesses to healthcare providers. Finally, optimised devices can also help to encourage long-term product confidence among patients who have never used the originator biologic, further incentivising manufacturers to explore device enhancements.
References
[1] Iqvia, The Impact of Biosimilar Competition In Europe, October 2019
[2] IQVIA Institute for Human Data Science, Biosimilars in the United States 2020–2024: COMPETITION, SAVINGS, AND SUSTAINABILITY, October 2020
[3] European Medicines Agency, Guidance, Biosimilars in the EU, 2019