Competitive Entry

Management Summary

For biosimilar manufacturers looking to compete with original biologic medicines whose patents expire between 2018 and 2023, the available market is estimated at $3.12 billion per year in Europe and $5.24 billion per year in the United States.

The successful adoption of biosimilars depends on a number of factors: confidence from clinicians in the biosimilar product; more competitive drug pricing enabled by greater competition; and patient trust in the drug delivery device.

This paper highlights evidence for why well-designed devices can make it easier for biosimilars to be adopted. It also emphasizes the importance of research with patients and healthcare professionals to understand what they prefer in a device, along with the essential steps needed in the design process to develop the best possible delivery system.

Biosimilars – the new wave 2018-2023

As the pharmaceutical industry enters the 2020s, biologic medicines are projected to deliver significant therapeutic benefits and long-term cost savings for health systems worldwide. As one study¹ explains, “…biologics may increase drug costs. However, biologics offer demonstrated improvements in patient care that can reduce expensive interventions, thus lowering net healthcare costs.”

Beyond these patient benefits, introducing biosimilars following the expiration of the original biologic medicine’s patent has been associated with price reductions due to healthy competition. This leads to greater patient access and is another driver for adopting biosimilars. In the long term, price discounts need to reach a sustainable level – where savings for the market are balanced against manufacturers’ incentives to continue investing in new drug discovery, development, and regulatory approval.

The EU already leads with more approved biosimilars—59 referencing 18 medicines²—than the United States (17 referencing 9 medicines³). Still, today’s European biosimilar count is only a small part of what’s expected to be available soon.

From 2018 to 2023, seventeen biologics will have come off patent in Europe. In the U.S., the number is fifteen. The arrival of biosimilars has led to price discounts around 30% in the European Union⁵ (though discounts may be much higher in some countries). Reviews of national biosimilar competition policies show that mandatory discounts, where required, typically fall within the 20-40% range compared to reference product prices⁶.

Encouragingly, early results from a developing U.S. competitive market for a biologic⁷ whose patent expired in 2015 show that prices have already been discounted by 25% off the branded drug, and the market expects this discount may rise a bit further before stabilizing into sustainable competition⁸.

This paper analyzes biologics losing patent protection over the five-year period 2018-2023⁹ to provide an overview of the competitive biosimilar market. In Europe, the market opportunity for biosimilar manufacturers¹⁰—after factoring in discounts and assuming 50% market share—is $3.12 billion per year at current revenues. The comparable market in the USA is $5.24 billion per year.

Switching

There are a variety of clinical and regulatory challenges associated with switching patients from original biologics to biosimilars¹¹. Although not the main focus of this paper, it’s important to note that while global health regulators continue to act cautiously in designating biosimilars as interchangeable, their confidence is quickly growing as more real-world evidence becomes available (additional independent studies¹² continue to show that switching patients to biosimilars is effective and generally well-tolerated).

Overall, healthcare regulators, executives, and clinicians worldwide are interested in encouraging biosimilar adoption whenever it benefits the patient. For example, in the UK, NHS England now encourages commissioners, providers, and patients to proactively and collaboratively realize cost savings by switching to biosimilar therapies¹³. More generally, after over a decade of clinical experience in the EU, confidence regarding the safety and effectiveness of biosimilars for approved uses has grown, reducing earlier worries, especially when starting treatment in patients new to therapy¹⁴. Additionally, regulators are taking steps, or have already done so, to enable interchangeability when clinicians consider it safe¹⁵.

Device Design and Switching

A growing number of experts now stress that the design of the drug delivery device—usually an auto-injector or prefilled syringe—plays a crucial role in making switching possible after clinical judgment¹⁶. This is important for two reasons. First, large-molecule biologics are often more viscous, which presents challenges related to the volume to be administered and possible pain during injection. Weekly injections are typical for treating conditions like rheumatoid arthritis. At the same time, health systems around the world are moving toward patient self-administration to reduce pressure on hospitals and make therapy more convenient for patients¹⁷.

Several studies recognize the importance of easy-to-use drug delivery devices, and the FDA now requires human factor studies to support device design and demonstrate that user risks are identified and mitigated. One such study—focused on synthetic insulin—summarized it this way¹⁸:
“While regulatory guidelines cover aspects like structure, PK/PD, efficacy, safety, and immunogenicity of a biosimilar, one factor equally important is the delivery device. Delivery devices matter to the patient’s experience with insulin; regular use becomes part of daily life. While precise dosing is essential, ease of use, comfort, and convenience of the device also significantly affect adherence and, in turn, efficacy. Familiarity and comfort with a delivery device may encourage patients to stay loyal to a brand-name insulin, even when cheaper biosimilars are available. Conversely, if patients must switch to a new manufacturer’s product, a new or different device may discourage switching.”

Increasingly, the drug delivery device is seen as a fundamental part of treatment—the pairing of drug and delivery system (a ‘combination product’ per the FDA) is managed by its own regulatory pathway. As another study¹⁹ explains, “Products may be offered in forms different from their reference products; without proper instruction from a healthcare provider, this could result in misuse by patients or caregivers. FDA guidance requires sponsors to provide supporting data and performance testing for the device component of the proposed interchangeable product.” More evidence comes from the fact that pharmaceutical companies are establishing exclusive partnerships with device makers to gain a competitive edge during switching and retention²⁰.

To sum up, experts broadly agree on the critical impact of drug delivery device design, with one noting, “It is […] important to consider differences between biosimilar delivery devices and reference products that may offer extra value to patients and providers²¹.” Likewise, device choice affects adherence: “From the patient’s point of view, switching to a follow-on biologic can require using a different device, which may create challenges for adherence and dosing²².” New designs made specifically for biosimilars often bring features that enhance usability for patients. Making devices easier to use helps encourage new users to follow their treatment plans, while existing users—especially those with degenerative illnesses like osteoarthritis—are likely to place even more value on user-friendliness over habit.

A case in point

There are two main factors in the world of biologics and biosimilars. First, clinicians want to bring the benefits of biologic therapies to as many patients as possible, supporting adherence and accurate self-administration. From a business point of view, new biosimilar entrants aim to make it easier for patients to switch—including by focusing on device design—while makers of the original reference drugs seek to keep patients, clinicians, and nurses loyal to their brand after patent expiry.

Research is essential to measure strength of preference for a specific device design, from both healthcare professionals and patients. Some details from a study by Owen Mumford Pharmaceutical Services show just how much can be learned by this kind of research.

The study compared an original biologic and a biosimilar competitor.

The original biologic used a push-button delivery device as its combination product. The biosimilar, in contrast, featured a pressure-activated auto-injector. The research focused on understanding preferences between these two types of device.

Existing users of both drugs showed a strong preference for the device type they were used to—habit was a powerful factor. But, for patients new to therapy, 60% said they preferred the pressure-activated device. Nurses—especially in the U.S.—favored the pressure-activated device as well. Preference for the push-button design was much weaker than for the pressure-activated design. The study also looked at perceived ease of use as a separate issue from overall preference. Both types were seen as easy to use.

These findings provided a basis for pharmaceutical companies and device manufacturers to develop product design strategies, including short-term tactics to build customer preference, and longer-term plans to encourage patients to transition from one device type to another with the support of communications and educational materials for both clinicians and patients.

Key Design Issues

Once research on patient and healthcare professional preferences is complete, the device development process should follow a thorough series of steps. Expert opinions²³ generally group these as follows:-

1. Choosing the right primary container; assessing interactions with the drug; impact on drug stability; manufacturing process compatibility.
2. Meeting regulatory standards; design reviews; human factors studies; managing device risk; developing and verifying test methods; risk and confidence factors.
3. Evaluating device candidates; robustness and usability for target uses; risks in assembly and manufacturing; supply chain reliability; environmental and disposal risks; performance after shipping.
4. Design control measures; complete planning and documentation; design review processes; operational transfer methods; post-launch monitoring.
5. Assessing manufacturability and risk for control strategies; covering device and combination product; vendor site controls.
6. Packaging factors; shipping risks; probable packaging complaints.
7. Biocompatibility; safe handling by patients/users; following ISO10993 standards.