Biologic therapies derived from living organisms have revolutionized the treatment of complex diseases, yet their high development costs are often passed onto patients. Biosimilar drugs offer a promising solution to reduce costs while maintaining therapeutic efficacy. Unlike generic drugs, biosimilars cannot be exact replicas of their reference biologics due to their complex structures, necessitating rigorous testing and regulatory approval. Microcalorimetry, specifically Differential Scanning Calorimetry (DSC), plays a crucial role in this process by assessing the thermal stability of biosimilars to ensure they are structurally similar and perform equally to their reference drugs. In this blog, we examine why testing is crucial in the regulatory process and how instruments like the DSC are helping usher an influx of biosimilars to patients who need them.

Biologic treatments–those sourced from living things like proteins, stem cells, or genetic material–have saved and improved billions of lives. You, or someone you care about, has benefited from their unique ability to tackle some of our trickiest and deadliest diseases, be it insulin to control and treat diabetes, the mRNA vaccines that curbed and reversed the global COVID-19 pandemic, or immunotherapies helping to slow and reverse deadly cancers.

These pharmaceutical breakthroughs have, no doubt, made the world a healthier place, but not without requiring billions of investment dollars in research, development, and commercialization. That cost is ultimately passed on to insurance companies, healthcare providers, and patients themselves. Fortunately, there is a burgeoning solution to curb cost and increase access: Biosimilar drugs.

In this blog, we examine why biosimilars–despite offering comparable benefits to their “generic” small-molecule drug counterparts–undergo a more stringent regulatory process and how testing for thermal stability using Differential Scanning Calorimetry (DSC) is a critical step in ensuring these therapies function safely and effectively when they reach the patients who rely on them to stay alive.

Like generic drugs, biosimilars can be developed and prescribed once their breakthrough name-brand counterparts’ patent expires. Yet there’s one fundamental difference.

• Generic drugs have a small-molecule structure that is an exact copy of the original name-brand version. Think of Advil (the name-brand) and ibuprofen (the generic) or Lipitor and atorvastatin. The ability to reproduce a structurally perfect copy means a far more straightforward approval process. It also allows pharmacies to fill name-brand prescriptions with generic versions without additional testing or regulation.
• Biosimilars are precisely as the name suggests–similar versions to their name-brand biologic. Because they are sourced from living components, their structures are enormously complex. A perfect copy is impossible. That means, even if their treatment efficacy is the same, they require far more stringent testing and regulation before reaching the market. In particular, if the developer wants to create a therapy that will safely replace or interchange with the original treatment under the same prescription.

Both biosimilars and generics provide similar benefits to patients. More options mean easier access and lower cost. Yet a biosimilar’s journey from lab to patient is more complicated, which is why there are far fewer in the market.

Global regulatory agencies require a biosimilar to meet a specific set of criteria before entering the market. Despite not being molecularly identical to their name brand, a biosimilar must:

1. Use the same “mechanism of action:” The way in which the biosimilar interacts with, controls, or fights the illness must be identical to the original drug.
2. Use the same “route of administration:” If the original is administered through an injection, a patch, or a pill, the biosimilar needs to be delivered through identical means.
3. Be manufactured with a similar potency, purity, and dosage: The biologic’s efficacy can’t rely on more or less treatments or volume.
4. Undergo clinical trials to approve efficacy: However, this process is faster and less strenuous because the original biologic has already endured rigorous study. Which, of course, is why biosimilars are more affordable.

The goal, ultimately, is to ensure the biosimilar performs as well as its counterpart so that, even though it is slightly different at the micro level, it still provides the same effective treatment. But getting there doesn’t just require human trials; testing the formulation’s structure and stability in the lab is a critical early step.

In the past 15 years, countries worldwide have adopted similar regulatory processes to develop, test, and approve biosimilar drugs. Each includes an “Analytical Similarity Assessment“: a series of independent lab tests to prove that the structural properties of the biosimilar closely match the name brand.

‘Conformational Stability” is a fundamental component of the assessment. This tests how the drug’s structure changes through varying temperatures, time, or both. Researchers commonly use a specialized instrument called a Differential Scanning Calorimeter (DSC) to capture the necessary data for the assessment. The tool allows researchers to examine how multiple samples of a given compound transform or react to minute, precisely controlled temperature changes. To be considered a biosimilar, a new therapy must react to heat in the same way as the original biologic. Tools like the Nano DSC offer automated throughput and the highest level of measuring sensitivity to extract vital data during the regulatory process for low dose antibody drug products. Which means it is highly likely, and increasingly necessary, that the biosimilar drugs used in treatment today underwent some form of DSC testing.

The one disadvantage of traditional DSC instruments is that high concentration drug products require dilution to avoid damaging a fixed cell. The new TA Instruments RS-DSC solves this by using disposable micro fluidic chips, allowing for formulations with concentrations >20 mg/mL to be tested in their natural state, quickly and at scale. Ultimately, this provides the most accurate thermal stability data possible while mimicking real-world conditions.

Even if a biosimilar is approved, one additional regulatory hurdle must be surmounted for ubiquitous accessibility. In an ideal scenario, a biosimilar could be swapped for the original biologic at any time during the treatment (if, say, there is a shortage of the name-brand option or the cost becomes prohibitive).

When this option is available, the biosimilar has been approved for “interchangeability.” The drug has undergone human clinical trials and significant lab testing to ensure it behaves precisely the same way as its peer. This additional process differs from generic small-molecule drugs. Because they are functionally identical to their originals, this extra approval isn’t necessary.

But a biosimilar drug’s stability and efficacy can sometimes change, even when stored in the exact same conditions. Which is why testing, at the micro level, how and why the formulation changes compared to the name brand is critical. That can only be done prior to the human trial in a lab using a bevy of instruments, including DSC.

When more biosimilars reach commercialization, global healthcare becomes more accessible and equitable. It’s great news, then, that expiring patents and development innovations will ensure an influx of biosimilars in the near future. But the stringent, regulated process required before reaching patients is vital. Testing, whether done during human trials or earlier in the lab using DSCs along with other instrumentation, ensures that no matter where the treatment comes from, it’s as safe and effective as the blockbuster drug that inspired it.