Our Regulatory Strategy & Policy Team at Samsung Bioepis is dedicated to shaping the regulatory environment involving policies, regulations and/or enforcements that are associated with biopharmaceutical industry, especially biosimilars, and make sure that the company’s voice is heard and fairly represented. The ultimate goal is to support access to quality-assured, safe and effective biosimilars globally.

To achieve this, the team engages with regulators and decision-makers, participates at trade associations, contributes to the peer-reviewed literature and takes press questions. The team’s latest contribution has been published by the Generics and Biosimilars Initiative (GaBI) and is titled “US interchangeability designation: are we ready to cut the Gordian knot?”. This blog reiterates the keys point addressed in the peer-reviewed article.

As biosimilars become more available in the US, they help reduce the often high costs associated with biologic therapies and facilitate access for more patients, including earlier in their disease. Biosimilars, which are highly similar to already-approved originator biologic medicines, are designed to provide the same therapeutic benefits at a more affordable price. However, achieving the additional U.S. Food and Drug Administration (FDA) designation of interchangeability can be a significant regulatory hurdle. This designation which enables substitution of a biosimilar for its reference biologic by a pharmacist (subject to state law) without a physician’s prior approval. Interchangeable biologics are not better biosimilars; they are the identical product with an additional regulatory designation from the FDA.

The FDA has evolved their approach to issuing this designation of interchangeability. To be designated as interchangeable, a biosimilar must not only demonstrate that it is as safe and effective as the reference product, but also that switching between the biosimilar and the reference product does not negatively impact patient outcomes. In some cases, this has led to additional clinical studies, often increasing the cost and time required to bring interchangeable biosimilars to market.
 

While there are some advocates for maintaining these additional study requirements, it is increasingly apparent that they provide no new regulatorily-actionable information. They argue that the FDA’s strict requirements for interchangeability are essential to safeguarding patient safety and maintaining trust in biosimilar therapies. Given that biologics are often used to treat complex, chronic conditions such as cancer, rheumatoid arthritis, and autoimmune diseases, ensuring that patients do not experience diminished efficacy or unexpected side effects when switching between treatments is clearly of paramount importance. However, FDA no longer sees regulatory value in such studies and also recognizes that the additional clinical trials, while adding significant financial and regulatory burdens, offer no benefits in terms of altered patient outcomes. It is easy to assume that a clinical question can only be answered through clinical studies, but this is not the case when the analytical and functional testing already completed to develop and approve a biosimilar is so much more sensitive than a clinical trial. Biosimilars are already subject to such rigorous testing in order to meet high standards of safety and efficacy before being approved, making the extra hurdles for interchangeability redundant. Unnecessary studies on humans are always to be avoided as they lack ethical validity too.

Educating health care providers on FDAs in depth evaluation of biosimilars, and explaining why extra clinical studies are not helpful remains important. Confidence in biosimilars is critical to their expanded use, but will always be a wholly different need from an approval decision by a regulator. Conflating the two issues is common. This confusion is impeding the full adoption of biosimilars in the US and that hurts patients’ access. Given that most biologics, including biosimilars, are administered by the physician that prescribes them, in reality there is no opportunity for substitution by a pharmacist. The interchangeability designation is about dispensing by pharmacists, not prescribing by physicians. Hence, it is not relevant to prescribers, and they should not expect all biosimilars to be so designated.

So is the US ready to "cut through" this regulatory complexity and simplify the way forward? FDA would appear to be keen to do so, but there are statutory constraints with which the Agency must complyⁱ. For sponsors, the financial implications are significant and impacts the biosimilars that they choose to develop. Widespread use of biosimilars, whether designated as interchangeable or not, could result in substantial savings for both patients and healthcare systems, particularly in chronic disease management where biologics are the best long-term treatment solution, but regulatory predictability is key. And likely future originator biologics development is impacted too.

Despite the challenges, the potential benefits of increased biosimilar adoption are clear. Biosimilars have been shown to reduce treatment costs by 15-30%, and as more biosimilars enter the market, these savings are expected to grow^ii,iii . A streamlined process for interchangeability, or indeed all biosimilars being designated as interchangeable upon initial approval, could accelerate this trend, helping to make life-saving treatments more accessible to a broader population.

Collaboration between regulators, healthcare providers, and manufacturers has already ensured that the biosimilars approved by FDA are safe and effective, and we need to ensure that they are affordable too. As the US continues to debate the meaning of interchangeability, it remains to be seen whether we are ready to fully embrace the biosimilars we have already available, and will unlock their potential to transform healthcare costs in the US as has occurred in Europe.