Biologics: An introduction to biologic drugs

Biologics are a comparatively new class of drugs, nonetheless based on an ancient principle: utilizing living organisms to obtain substances that positively affect health. This approach, however, has expanded from using, e.g., plant parts for curative reasons to biotechnological methods in biopharmaceutical manufacturing. These biopharmaceuticals now span from cell and gene therapy over antibody therapies to ADCs (antibody-drug conjugates) in cancer therapy.

In this article, we will provide more detailed information on this fascinating class of pharmaceuticals, including the exact definition, history, and manufacturing process of biologics.

Definition of biologics and the difference to conventional drugs

Biologics are a class of drugs derived from living organisms or their components – e.g. animals or microorganisms. These biological products are characterized by their complex molecular structures, often consisting of proteins, sugars, or nucleic acids.

Unlike conventional drugs, which are typically synthesized chemically or using plants and composed of small molecules, biologics are large molecule drugs. This distinction is important because the manufacturing process for biologic drugs involves living cells, which can result in a higher degree of variability compared to the more controlled synthesis of small molecule drugs. Additionally, biologics often target specific proteins or parts of the immune system, making them particularly effective for treating conditions with complex underlying mechanisms.^1 2 

The history of biologic drugs

The history of biologic drugs is marked by significant milestones in pharmaceutical development and regulation. Since the emergence of biologic therapies, particularly in the late 20th century, these treatments have revolutionized the field of medicine. The introduction of biologics offered new treatment options for various medical conditions, ranging from autoimmune diseases to cancer.

In 1982, insulin was developed by Genentech as the first biopharmaceutical – it was in this decade that the term “biopharmaceutical” was coined. Since then, more and more products have gained market access, with more than 300 to follow in the four decades to follow.^3 4 

Mechanism of action: How do biotherapeutics work?

Biotherapeutics employ a variety of mechanisms to exert their therapeutic effects, leveraging advances in gene therapy, biotechnology, and our understanding of the immune system. One key mechanism involves targeting specific cells or pathways within the body, such as T-cells or components of the immune system, to modulate immune responses and combat disease.

Gene therapy, a cutting-edge approach in biomedicine, aims to treat genetic disorders by introducing or modifying genes within target cells. By delivering therapeutic genes or gene-editing tools, gene therapy can correct genetic mutations or enhance cellular functions, offering potential cures for previously untreatable conditions.

Biologic medications, including monoclonal antibodies and cytokine inhibitors, function by binding to specific molecular targets involved in disease processes. For example, monoclonal antibodies may block inflammatory signals or neutralize harmful proteins, thereby alleviating symptoms and halting disease progression.

Generally speaking, there are four categories of biologics:

• Tumor necrosis factor (TNF) inhibitors
• Interleukin (IL) inhibitors
• B-cells inhibitors
• T-cells inhibitors

Sources:^9 10 

Biologics vs. biosimilars

Biologics and biosimilars are both types of biological drugs, yet differ in some aspects. Biologics are original therapeutic products derived from living organisms or their components. These drugs are complex in structure and require specialized manufacturing processes.

Biosimilars, on the other hand, are highly similar versions of approved brand name biologics, developed to be comparable in terms of quality, safety, and efficacy. They are produced via biotechnological methods as well, but unlike generic versions of small molecule drugs, biosimilars are not identical copies of their reference biologics due to the inherent complexity of biological molecules.

While biosimilars undergo rigorous comparative testing to demonstrate similarity to the reference biologic, including analytical, preclinical, and clinical trials, there may be minor differences in composition or the manufacturing process of biosimilars. However, these differences do not impact safety or effectiveness when used as intended.

Producing biologicals: Steps and practices in biomanufacturing

The manufacture of biologics involves a number of steps to ensure their safe and effective production. This chapter provides an overview of the practices within the biomanufacturing process, which may be found along upstream and downstream processes.

Upstream processes include cell line development, cell culture, and harvest, while purification and formulation are typical downstream steps. And in all of these phases, fluid and cold chain management plays a vital role.

Fluid management in biomanufacturing

Fluid management in biomanufacturing involves the precise control of liquids throughout the production process. This includes the transfer of media and reagents during cell culture, as well as the handling of harvested cells and purified proteins during downstream processing.

Challenges in fluid management arise from the need for precision and efficiency in dosing and mixing, as slight deviations can impact product quality and yield. Additionally, the risk of product loss due to leaks during fluid transfer poses efficiency challenges.

To mitigate these issues, biomanufacturers employ advanced technologies such as automated liquid handling systems and single-use disposable components. These aseptic filling solutions for biologics enhance precision, reduce contamination risks, and improve overall process efficiency.

Safe storage of biologics

Temperature-controlled storage of biologics is required for maintaining stability and integrity, ensuring their efficacy and safety throughout their shelf life. Biopharmaceuticals are often sensitive to temperature fluctuations, which can lead to degradation and loss of potency.

To provide temperature-controlled storage, biopharmaceutical companies utilize specialized storage freezers that maintain precise temperature ranges. These systems are designed to provide stable and uniform conditions, minimizing the risk of temperature excursions that could compromise product quality. Additionally, temperature monitoring systems are employed to continuously track storage conditions and alert personnel to any deviations.

Efficient strategies for manufacturing biopharmaceuticals

Efficiency is a major issue in the production of biopharmaceuticals, as their development and delivery process comes with considerable costs and time pressure. Therefore, biopharma companies are developing efficient strategies for manufacturing biologics, many of which being based on the implementation of single-use technologies.

Read more: How to optimize efficiency in biomanufacturing?

Single-use systems come with numerous benefits in biomanufacturing, from enhancing resource effectiveness thanks to a reduced need for cleaning to improvements in safety and efficiency in biomanufacturing.

Single Use Support drives these advantages even further, combining single-use technologies with advanced automated systems for fluid and cold chain management. Starting with single-use bags and RoSS® Shells as their protective secondary packaging solutions, bioprocess containers in various shapes and sizes have been created to thoroughly protect valuable drug products.

These can be filled into the bioprocess containers via Single Use Support’s RoSS.FILL – an aseptic filling system for different scales: It can both provide high throughput, particularly necessary for large-scale processes, and advanced accuracy for small-scale applications.

Once filled and protected by RoSS® Shell, biologics may be subjected to controlled freezing with RoSS.pFTU, Single Use Support’s plate freezing unit that allows to cater to the exact freezing protocols of different biologics down to -80°C. These freezing protocols are easily transferable to provide scalability from lab to commercialized manufacturing. And in case even lower temperatures are required, RoSS.LN2F stands out as the first cryogenic freezer to provide truly controlled freezing rates.

With the biologics now ready for storage in the ultra-cold storage freezer RoSS.FRDG or dedicated shipping solutions, biopharma companies and CDMOs are prepared to deliver their high-value products as precious tools in the fight against several types of medical conditions – fast, efficiently, and reliably.