Biologics are a type of drugs that are derived from living sources and have complex structures that make them difficult to replicate. Unlike small molecule drugs, which generic manufacturers can easily copy, biologics require a different approach to create similar products. These products are called biosimilars and are designed to be highly similar to the original, biologic medicines in terms of their safety, efficacy, and quality.
Biosimilars offer several benefits, such as lower costs, increased access, and more choices for patients and providers. However, biosimilars face several challenges, such as regulatory hurdles, manufacturing complexities, and market acceptance.
In this blog, we’ll explore what biosimilars are, how they are made, and their advantages and disadvantages.
What Are Biosimilar Drugs?
Most drugs on the market are small molecule compounds manufactured through chemical synthesis. After patents that protect the original small molecule expire, the manufacture of generics becomes viable. Generic drugs must contain exact copies of the active pharmaceutical ingredient as the originally protected drug.
In contrast, a growing segment of therapeutics known as biologics includes larger and more complex molecules. Biologics are produced and extracted from living organisms, consisting of antibodies, vaccines, or even cells. When patent protection expires from a biologic, the manufacture of biosimilars becomes viable. Unlike generics, a biosimilar product is not an identical copy of the original drug. Because living organisms create biologic drugs, they can vary slightly from batch to batch. This means that biosimilar drugs may differ from the biologic drug they are based on. However, a biosimilar must be shown to be highly similar to the reference product in terms of its safety, efficacy, and quality.
Despite a requirement to show safety and efficacy, several states in the US and countries in the European Union have raised regulatory issues holding back the wide use of biosimilar medicines. In response, a biosimilar can meet an additional set of more stringent requirements to be labeled an “interchangeable biosimilar.” This additional designation is meant to instill confidence in the safety and effectiveness of biosimilar medicines.
What Are the Benefits of Biosimilars?
One of the main benefits of biosimilar drugs is that they provide lower-cost alternatives to the original biologic medications, which are often expensive and may be unaffordable for some patients or health plans. Biosimilars may reduce costs by offering a lower-price treatment option and increasing market competition. This may lead to immense savings in public health spending and free up resources for other health needs.
Another benefit of biosimilars is their increased access and choice for patients and providers. Biosimilars may enable more patients to receive biologic treatments for various chronic and severe conditions, such as cancer, diabetes, arthritis, and inflammatory bowel diseases. They may also provide more treatment options for patients and providers, allowing them to choose the best therapy for each case. Biosimilars may also improve health outcomes by increasing adherence and reducing treatment interruptions due to cost or availability issues.
How Are Biosimilars Made?
Because researchers make biosimilars from living sources, such as cells or microorganisms, these drugs have complex structures that cannot be exactly replicated. The process of biosimilar development can be broken down into seven phases:
- Preparation of the material. This involves obtaining the raw materials, such as cell lines, culture media, and reagents, that are needed for the production of the biosimilar.
- Preparation of fluids. This involves preparing the solutions and buffers that are used for the cultivation and purification of the biosimilar.
- Cellular expansion. This involves growing the cells that produce the biosimilar in bioreactors under controlled conditions of temperature, pH, oxygen, and nutrients.
- Harvesting. This involves separating the cells from the culture medium and collecting the biosimilar product from the supernatant.
- Purification process. This involves removing impurities and contaminants from the biosimilar product using various techniques, such as filtration, chromatography, and electrophoresis.
- Packaging. This involves filling and sealing the biosimilar product in vials or syringes under sterile conditions.
- Quality control procedure. This involves testing the biosimilar product for its identity, purity, potency, safety, and stability using various methods, such as biochemical assays, immunological assays, and physicochemical tests.
Biosimilars undergo a rigorous approval process by the Food and Drug Administration that requires extensive data and evidence to show their similarity to the original biologic in terms of structure, function, quality, safety, and effectiveness. Compared to the original biologic products, biosimilars may offer lower-cost alternatives and increase access and choice for patients and providers.
As the demand for biosimilars grows and more of these drugs are approved, contract development and manufacturing organizations (CDMOs) are expected to play an essential role in their production. CDMOs provide expertise and services for developing promising drug candidates and are a valued resource for emerging biotech and biopharma companies as well as medium and large firms.
What Are Examples of Biosimilars?
Humira (adalimumab) is a biologic medicine that is used to treat various inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. The biologic drug is injected under the skin and works by blocking a protein called tumor necrosis factor-alpha (TNF-alpha), which can cause inflammation and damage tissues and organs.
Amjevita (adalimumab-atto) is a biosimilar to Humira that received FDA approval in 2016. Amjevita has the same active ingredient, dosage form, route of administration, and strength as Humira. However, Amjevita is not approved for all the same indications as Humira. For example, Amjevita is not approved to treat hidradenitis suppurativa or uveitis. Amjevita is also not interchangeable with Humira, meaning that a pharmacist would need approval from the prescriber to switch between the two products. The manufacturer of Amjevita, Amgen, has been working on performing switching studies to gain interchangeable status.
Lantus (insulin glargine) is a long-acting form of insulin used to control blood sugar levels in people with diabetes. Insulin is a hormone that helps muscle, fat, and liver cells absorb glucose from the bloodstream and use it for energy. Lantus is injected under the skin and provides a steady amount of insulin throughout the day and night, mimicking the pancreas’ natural basal secretion of insulin.
The FDA approved Semglee (insulin glargine-yfgn) as a biosimilar to Lantus (insulin glargine) in July 2021, the first FDA-approved interchangeable biosimilar insulin product. Semglee is also the first insulin product to go through the biosimilar approval pathway, as insulin was not officially considered a biologic until March 2020. The approval of Semglee as a biosimilar and interchangeable product was based on evidence that showed the products are highly similar and that there are no clinically meaningful differences between Semglee and Lantus regarding safety, purity, and potency (safety and effectiveness).
Biosimilar Drugs for Cancer Treatments
Biosimilars are used in cancer treatment in different ways, depending on the type of cancer and the type of biologic medication they are modeled after.
Some biosimilars help the body’s immune system recognize and kill cancer cells more effectively, such as rituximab (Rituxan) and its biosimilars truxima, ruxience, and riabni. Rituxan and its biosimilars work by attaching to a protein called CD20 on the surface of B cells and causing them to die. These biologics can be used alone or with other medications to treat non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) as maintenance therapy, a treatment to prevent or delay cancer from coming back or getting worse.
Other biosimilars are used to help the body make more blood cells to replace the ones lost because of other cancer treatments, such as filgrastim (Neupogen), pegfilgrastim (Neulasta), and epoetin alfa (Epogen) and their biosimilars zarxio, nivestym, releuko, fulphila, udenyca, ziextenzo, nyvepria, fylnetra, stimufend, and retacrit. Neupogen and its biosimilars are not cancer drugs but supportive care therapeutics that help the body cope with the effects of cancer treatment. These biologic medications are used to prevent or treat neutropenia, a low level of white blood cells called neutrophils that can increase the risk of serious and life-threatening infections. Neutropenia often occurs between 7 and 12 days after receiving chemotherapy.
Still other biosimilars are used to treat specific types of cancer that have certain genetic features, such as trastuzumab (Herceptin) and its biosimilars ogivri, herzuma, ontruzant, trazimera, and kanjinti. Patients are tested to determine whether tumors express the HER2 protein using immunohistochemistry or in situ hybridization. Herceptin and its biosimilar products are used to treat HER2-positive breast cancer.
That’s a Wrap
In summary, biosimilars are similar, but not identical, to the biologic that they’re mimicking. Biosimilars may offer lower-cost alternatives to biologic drugs and increase access and choice for patients and health care providers. However, biosimilars face regulatory hurdles and market barriers that may limit their adoption and use. Understanding the differences and similarities between these medications is essential for making informed decisions about health care and treatment options.
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