Top Challenges Facing Biosimilar Adoption and Manufacturing

What Are Biosimilars? 

Although generics and biosimilars are often compared, generic drugs are typically small-molecule drugs with the same active ingredient as their brand-name counterparts. In contrast, biosimilars are the analogue of generics for larger biologic drugs.

On their own, biosimilars are defined as biologic drugs that function similarly — without clinically meaningful differences — to FDA-approved biologic therapies. The originator brand-name medication is also known as a reference product. A biosimilar should have the same route of drug administration, side effects, and strength as the original biologic product.

Despite the similarities between biologics and biosimilars, the formulary has some variations. Regulatory rules prevent biosimilars from being an exact copy of the brand-name drug.

In 2010, Congress passed the Biologics Price Competition and Innovation Act, which established an abbreviated regulatory process for biosimilars and paved the way for their approval.

FDA stated that it approves biosimilar products and provides the scientific and regulatory advice needed to bring safe and effective biosimilars to market. As of June 7, 2023, the FDA has approved 41 biosimilar products.

The first approved biosimilar was filgrastim-sndz (Zarxio) in 2015, used to prevent infection during chemotherapy. Other notable biosimilar approvals include the following:

• Adalimumab-adaz, a Humira biosimilar
• Bevacizumab-awwb, the first approved biosimilar for Avistatin
• Infliximab-dyyb, a remicade biosimilar
• Rituximab-abbs, a retuxin biosimilar

More recently, in May 2023, the FDA approved adalimumab-aaty, another Humira biosimilar.

Biosimilar Adoption and Healthcare Spending

Comparable to generics for small molecule drugs, biosimilars, a cheaper alternative to biologics, may offset rising drug prices.

According to a 2020 IQVIA report, biosimilars are, on average, 30% less expensive than their brand-name counterpart. Despite having fewer price cuts than generics, a 30% decrease in drug costs can significantly reduce overall healthcare spending directly and indirectly.

From a direct cost-saving perspective, having a less expensive interchangeable product should reduce payer spending and out-of-pocket costs. Less acknowledged but equally as important, cheaper alternatives to critical drugs can improve patient medication adherence, reduce medication rationing, and prevent adverse events from cost-related medication nonadherence. Overall, the indirect savings could also have a significant benefit over time.

According to a 2022 Vizient survey, the use of biosimilars has saved the United States $12.6 billion between 2014 and 2022, with applications in oncology, immunology, endocrinology, and more.

Although these medications have saved costs domestically, a 2022 study published in JAMA Network Open implies that biosimilars can be sold at an even lower cost. The data shows that biosimilars in the US are 55–90% of the reference product market price.

Germany and Switzerland’s biosimilar pricing upon market entry were 65–100% and 70–80%, respectively. However, an in-depth analysis showed that the US's average monthly treatment cost with a biosimilar was 1.94 times greater than Germany’s and 2.74 times higher than Switzerland’s.

Some experts hypothesize that vertical integration of pharmacy benefit managers (PBMs) may impact biosimilar costs. An American Medical Association (AMA) analysis noted that PBMs, often used for rebate negotiation, retail network management, and claim adjudication, may impact drug costs.

However, in an AMA press release, AMA President Jack Resneck Jr, MD, commented, “PBM markets require careful scrutiny as less competition and more vertical integration can embolden anti-competitive business practices to the detriment of patients. The novel data presented by the AMA analysis is intended to help regulators, lawmakers, researchers, and policymakers better evaluate merger proposals in the future that may harm patients by raising prices, lowering quality, reducing choice, and stifling innovation.”

Biosimilar Adoption Challenges

Despite the benefits and cost savings associated with the use of biosimilars, challenges related to the production and interchangeability of biosimilars have caused hesitancy among healthcare professionals.

Biosimilar Regulation and Interchangeability

Like generics, biosimilars undergo a shorter FDA approval process than the brand-name biologics they are meant to replace. Even so, the FDA notes, “The FDA often needs more information from studies comparing a biosimilar to its original biologic than it needs from studies done on a generic drug. This is because a biosimilar comes from a natural source and cannot be made as an exact copy of its brand-name biologic.”

One of the greatest challenges in biosimilar adoption is FDA interchangeability approval. Although a biosimilar can treat its target disease upon FDA approval, a second layer of approval is necessary to consider the drug interchangeable with its brand-name biologic.

According to the FDA’s Interchangeable Biologic Product Fact Sheet, “For approval as an interchangeable biosimilar, manufacturers must provide additional data that reflect how the interchangeable biosimilar may be used in the marketplace with patients. Like generic drugs, patients receiving their medications through their pharmacies may switch between a brand-name biologic and an interchangeable biosimilar.”

This data often includes clinical trials where one group of patients alternated between the reference product and the interchangeable biosimilar while the other remained on the reference product. Assuming the manufacturer can show that the efficacy and safety of the products are equal, the drug can be deemed interchangeable.

Once a drug is marked as interchangeable, pharmacists can replace a biologic prescription with a biosimilar without the additional input of a prescriber. Interchangeability benefits multiple stakeholders, improving patient access, reducing healthcare system costs, and expanding medication adherence.

Manufacturing Biosimilar Drugs

Biosimilar manufacturers also face a series of challenges throughout the manufacturing process. Standardizing the product can be challenging because biosimilars, like their reference drugs, are produced through living systems.

Beyond that, these molecules can be less stable than small-molecule drugs synthesized from chemicals.

Biosimilar Education

Another challenge preventing the adoption of new biosimilars is the education barriers. While these alternatives can reduce healthcare costs, providers must be comfortable with their use and familiar with interchangeability guidelines.

According to an insight report by Cardinal Health, in 2022, 62% of rheumatologists felt “very comfortable” prescribing biosimilars; however, this number needs to rise to increase biosimilar adoption, expand their market share, and present incentives for biosimilar development.

Despite the need for additional familiarity and comfort, data has shown an upward trend among providers. “The growth in familiarity and comfort, first and foremost, is just increased time and experience of these products on the market and the growing number of products on the market,” emphasized Sonia Oskouei, PharmD, in a 2022 interview with PharmaNewsIntelligence. “The second reason is the anticipation of 2023. This is a landmark year that many stakeholders are excited to see play out and eager to see it play out.”

Attempting to improve biosimilar education, the Accreditation Council for Medical Affairs (ACMA) launched a self-paced, online board certification program for biologics and biosimilars. The program is open to healthcare professionals with an MD, PharmD, PhD, DO, DNP, NP, PA, BPharm, PsyD, or a bachelor’s degree and two years of relevant industry experience.

Increasing Biosimilar Market Competition

In addition to addressing the challenges associated with biosimilar adoption and development, it is critical to encourage marketplace competition. Competition in the pharmaceutical marketplace is a typical tool to lower prices and widen medication access.

Although many initiatives have worked to incentivize biosimilar development and adoption, regulatory involvement is critical for expanding the biosimilar market.

“Competition doesn’t happen by itself,” Amitabh Chandra, MD, Harvard University’s John F. Kennedy School of Government, said in a Health Affairs analysis. “To get biosimilar competition to work, we will need regulations that remove market blockages. These measures can range from preferential use of biosimilars in Medicare and Medicaid, all the way to compulsory licensing when exclusivity periods expire.”

Adopting biosimilars across multiple healthcare settings, including in-patient care, specialty pharmacy, and primary care, can improve market competition, driving down drug prices and providing alternatives to reference biologics. Despite the challenges associated with adoption, pharmaceutical innovation in this healthcare sector is critical for medication access and health equity.