Biosimilar development in the United States is at an important juncture, reports Darren Mansell, Regulatory Affairs Manager, Owen Mumford
Currently, almost a fifth of the biologics market, worth $211 billion dollars, is exposed to biosimilar competition. Furthermore, 64% of the market, or $135 billion, comprises molecules with the potential for biosimilar development. Half of these molecules already have biosimilars in the pipeline.1
As manufacturers seize this opportunity, they will also need to assess how they can stand out in what will become an increasingly crowded market. With ease-of-use being a high priority for patients, and in light of the growing trend towards patient self-administration, there is an opening for biosimilar manufacturers to innovate in the area of drug delivery.
Patients are not unaccustomed to the brand of their drug products changing, whereas the choice of drug delivery device may play a critical role in retaining patients in the long-term if their overall experience can be improved.
However, as the biosimilar market develops, regulatory processes have followed suit. In 2019, the US FDA issued its final guidance document, titled “Considerations in Demonstrating Interchangeability with a Reference Product.”2
The aim of the guidance is to help sponsors to demonstrate that their biosimilar product can substitute for a reference biologic without the intervention of the prescribing healthcare provider.
The document is ambiguous when it comes to changes in the drug delivery device … and this may serve to stifle innovation, setting back improvements in the patient experience.
This article seeks to clarify the guidance, observing the FDA’s willingness to discuss and review device changes. It will also assess how companies who take advantage of this route can benefit, not only in gaining competitive advantage, but also by leading the way for others in their field.
Looking to Europe provides a useful reference point on regulatory attitudes towards the drug delivery device, as the EU made an early start in developing regulatory pathways for biosimilars.
The first biosimilars guidance was issued in the EU, in 2005, and 58 biosimilars have been approved for 16 reference biologics.3,4 In comparison, the FDA, which issued its first draft guidelines in 2012, has now approved a total of 26 biosimilars for nine reference products.
Guidance from the European Medicines Agency separates the drug from the delivery device, and this facilitates innovation in the device component. Differences in the administration device may be allowed as long as there is no impact on safety and efficacy.5
This means that biosimilar producers, or even biologics originators, can improve the usability of a device and thereby gain a competitive edge in the process of switching or retention.
In fact, there may also be scope to change the mode of delivery. In one example, the manufacturer was able to develop a biosimilar that is suitable for subcutaneous administration, whereas the reference biologic is usually administered intravenously.6
Not only does this enable self-administration, giving patients greater control of their own treatment and easing some of the burden on healthcare services, but the subcutaneous version also improved the effectiveness of the therapy.
As the FDA has a dedicated approval pathway for combination products, in which both the drug and device are assessed together, the guidance on biosimilars includes additional considerations for developing container closure systems or device constituent parts — such as safety syringes or autoinjectors — which will deliver the interchangeable product.
As well as combination product manufacturers, it is important that contract manufacturers of drug delivery devices take note of these considerations. They may be asked to support pharmaceutical companies with the regulatory approval process of the final product integrating their device.
Manufacturers looking to improve or enhance a delivery device in a combination product may find the guidance contradictory.
The document initially advises against submitting an interchangeable product with a different “presentation” — that is, the device component — from the approved reference product.
The example provided is that, if a reference product is only marketed in a vial and a prefilled syringe, a sponsor should not seek approval for the proposed interchangeable product for a different presentation, such as an autoinjector.
However, the document then proceeds to invite sponsors to approach the FDA if they are considering any divergence from the licenced reference product. The FDA will then evaluate whether the proposed presentation could support a demonstration of interchangeability.
To navigate this lack of clarity, manufacturers must engage with the FDA as soon as possible to determine whether the proposed presentation is “similar enough” to the reference product, and then work with the regulator to develop an appropriate strategy.
This added hurdle to demonstrating interchangeability may deter some companies from adding device features that are not in the reference product.
In fact, in a recent survey, pharmaceutical businesses ranked regulation as their top concern when developing and marketing combination products for injection.7
Yet, despite this obstacle, pioneering pharmaceutical companies are taking stock of possible improvements that could be made to improve a patient’s experience with a device.
This is in line with the FDA’s increased emphasis on the importance of human factors in product development and creating ever-more patient-centric devices.
On the basis of this guiding principle, devices that promise to have an advantageous impact on patient adherence and outcomes ought to meet with a positive response from the agency.
Only as more organisations approach the FDA with proposed device developments will there be greater clarity around this issue, and this can only be beneficial for the pharmaceutical industry.
The increase in biosimilar approvals has the potential to bring enormous benefit to patients and healthcare systems, but this can only be achieved through patient acceptance and confidence.
Devices that can make the treatment of chronic conditions more comfortable for patients can certainly help to facilitate the switching process.
Additionally, with “biologic-naïve” patients, when switching is not necessary, innovative/enhanced devices will foster confidence in the overall combination product.
This is a further compelling argument to ensure that device enhancements have been properly explored … and it is likely to gain in significance as more biosimilars enter the market.