Biosimilars: the generics of biological medicines

When a patent expires on a conventional medicine, other manufacturers can produce generic versions. Generic medicines contain the exact same active ingredient as the original brand and are chemically identical. However, a growing number of modern treatments for conditions like cancers and autoimmune diseases are biological medicines. These are produced in living cells rather than through direct chemical synthesis. Because of how they are made, it is impossible to produce an exact copy of a biological medicine. Instead, when the patent on a biological medicine expires, other manufacturers can produce what are known as biosimilars.

Why biological medicines cannot have exact generics

Conventional medicines, such as painkillers or cholesterol-lowering drugs, are small molecules. They have a relatively simple, defined chemical structure that can be precisely replicated in a laboratory, meaning a generic version is chemically identical to the original. Biological medicines, by contrast, are large, highly complex molecules. They are manufactured using living organisms such as bacteria, yeast, or mammalian cells.

The living nature of the manufacturing process means that slight variations are inevitable. Factors like temperature, nutrient supply, and the specific cell line can influence the final molecule's structure, including how it folds or what sugars are attached to it. Because living cells are involved, even different batches of the same original biological medicine are not perfectly identical to each other. Regulatory bodies acknowledge that it is scientifically impossible to create an exact replica of a molecule made by living cells. Therefore, the concept of a generic biologic does not exist; instead, we have biosimilars.

How biosimilarity is demonstrated

A biosimilar is a biological medicine that has been proven to be highly similar to an already approved reference biological medicine. Regulatory agencies, such as the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and the South African Health Products Regulatory Authority (SAHPRA), require a rigorous step-by-step process to demonstrate biosimilarity.

First, manufacturers must use advanced analytical tests to compare the physical, chemical, and biological properties of the new medicine against the original. If the molecules are highly similar at a structural level, manufacturers must then conduct comparative animal and human clinical studies. The goal of these studies is not to prove the medicine works from scratch, but to prove that there are no clinically meaningful differences between the biosimilar and the reference product in terms of safety, purity, and potency. If approved, a biosimilar is considered a quality-assured medicine.

Global uptake and pricing impact

Biological medicines are often expensive to develop and manufacture, which can limit patient access. Biosimilars introduce competition into the market once the original product's patent expires. Generally, the introduction of biosimilars leads to a reduction in the prices of biological medicines. This price reduction improves access to essential treatments for chronic and life-threatening conditions.

The World Health Organization (WHO) recognizes the value of biosimilars and has established a prequalification programme to help lower- and middle-income countries access quality-assured biological medicines. In South Africa, biosimilars must be registered with SAHPRA and are subject to pricing regulations like the Single Exit Price framework, which helps ensure that savings from these medicines are passed on to patients and health systems. Many national health departments include both reference biologics and biosimilars on their essential medicines lists to help manage healthcare budgets.

Prescribing and substitution considerations

Because biological medicines and their biosimilars are not exact copies, they are not automatically considered interchangeable in the same way conventional generics are. In many countries, a pharmacist can substitute a generic for a brand-name small-molecule medicine without consulting the prescriber. With biosimilars, substitution policies vary significantly by region and product.

Some regulators require explicit physician approval before a patient is switched from a reference biologic to a biosimilar. Tracking the specific product is important for safety monitoring, as any adverse events must be attributed to the correct manufacturer. Patients and healthcare providers can verify the registration status, active ingredients, and pricing of both reference biologics and biosimilars using regulatory databases or search tools like HealthSA.