Biologics: An introduction to biologic drugs

micheal-eder

Michael Eder

May 8, 2024

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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 

Types and examples of biologics

Biologic drugs encompass a diverse array of therapies derived from living organisms or their components. One prominent type of biologic drug is monoclonal antibodies, which are engineered to target specific proteins or cells in the body. These antibodies have revolutionized possibilities in rheumatology and the treatment of various diseases, including autoimmune conditions like rheumatoid arthritis and psoriasis.

Another category of biologics includes vaccines, which stimulate the immune system to produce antibodies against specific pathogens. Vaccines have been instrumental in preventing infectious diseases such as hepatitis B and influenza, offering widespread protection to populations worldwide.

Cell-based therapies represent a groundbreaking advancement in biologic medicine, involving the transplantation of blood cells or tissues to treat conditions like leukemia or certain types of cancer. These therapies harness the regenerative potential of stem cells to repair damaged tissues and restore normal function.

Additionally, cytokines and interleukins are biologic molecules that regulate immune responses and inflammation. Drugs targeting these signaling pathways have shown promise in treating diseases characterized by dysregulated immune responses, such as rheumatoid arthritis and inflammatory bowel disease. Further types of biologics include blood components, somatic cells, hormones, tissues, and allergenics.

Examples of FDA-approved biologics and exemplary fields of application include:

  • Humira® (Adalimumab): Rheumatoid arthritis, Psoriasis, Psoriatic arthritis
  • Remicade® (Infliximab): Rheumatoid arthritis, Crohn’s disease, Psoriasis
  • Enbrel® (Etanercept): Rheumatoid arthritis, Psoriatic arthritis

Sources:5 6 7 8 

Biologics vs. Biosimilars – what’s the difference?

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.

Development and manufacturing of biosimilars: Challenges and opportunities

The development and manufacturing of biosimilars present both challenges and opportunities in the biopharmaceutical industry. One of the main challenges in producing biosimilars lies in achieving a high degree of similarity to the reference biologic while managing complex regulatory requirements. Developers of FDA-approved biosimilars must demonstrate comparability in terms of safety, efficacy, and quality through extensive analytical and clinical studies.

However, the development of biosimilars also offers significant opportunities, including expanding patient access to affordable biologic therapies and fostering competition in the market. Additionally, biosimilars have the potential to drive innovation and improve healthcare sustainability by providing alternative treatment options for patients with sometimes life-threatening conditions, stressing the need for efficient strategies for manufacturing biosimilars.

Biologics

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.

Freezing biologics

Freezing biologics is a necessary step prior to frozen storage and transport. Controlled freeze and thaw processes in the production of biosimilars and biologics offers distinct advantages over uncontrolled freezing, as it can help to maintain product quality.

Plate freezing provides uniform cooling to temperatures as low as -80°C, reducing the risk of inhomogeneous cooling and preserving a biologic’s integrity. They provide direct contact between containers or biologicals and the cooling plates, allowing direct and efficient heat transfer.

Innovative cryogenic freezers offer precise control over freezing rates down to even lower temperatures (around -170°C), allowing for tailored preservation conditions for biologics like certain gene-modified cell therapies.

storage-biologics

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.

Frequently Asked Questions

What are considered biologic drugs?

Biologic drugs, also known as biologics, are pharmaceutical products derived from living organisms or their components. These drugs are manufactured using biotechnological processes, such as recombinant DNA technology, to produce proteins, antibodies, nucleic acids, or other complex molecules. Biologics can include a wide range of products, such as monoclonal antibodies, cytokines, growth factors, hormones, vaccines, and gene therapies.

What do biologics do to the body?

Biologic drugs typically work by targeting specific molecules, cells, or pathways in the body's immune system, inflammatory response, or disease processes. Depending on their mechanism of action, biologics can modulate immune responses, inhibit inflammatory processes, promote cell growth or death, or interfere with disease-causing proteins.

What is the purpose of biologics?

The purpose of biologics is to provide targeted and effective treatment for a wide range of diseases. They have revolutionized the treatment landscape for many complex and difficult-to-treat conditions, offering new therapeutic options and improving patient outcomes.

What is a drug substance?

A drug substance is an active ingredient of a drug product, inserted in order to have a therapeutic impact on the person it is administered to.

What is the difference between API and bulk drug?

Bulk drugs, also known as active pharmaceutical ingredients (API), are ingredients of drug products that are inserted in order to have a biological impact on the person it is administered to.

What is the difference between a biosimilar and a generic drug?

The main difference between a biosimilar and a generic drug lies in their manufacturing processes and regulatory pathways. Generic drugs are chemically synthesized and are exact copies of their brand-name counterparts, known as small molecule drugs. They have identical active ingredients, dosage forms, and routes of administration. In contrast, biosimilars are developed to mimic a reference biologic as closely as possible. Due to the complexity of these large-molecule drugs, they are not identical to the reference product. Thus, they undergo a separate regulatory approval pathway that requires comprehensive analytical and clinical testing to demonstrate similarity in terms of safety, efficacy, and quality.

Freezing biologics: best practices

Freezing biologics – best practices

There is more than one way to prepare biologics for long-term storage under temperature-controlled conditions – in this article, we will explore some of the main freezing methods.

Automated aliquoting system: From small volume aliquoting to bulk filling with RoSS.FILL

Aseptic filling & processing of biologics

Many drug products require aseptic conditions along their entire production process. In this article, we will discuss essential considerations on aseptic filling in the biopharma industry.

storage-biologics

Safe storage of biologics: Requirements & solutions

Once biologics are produced, they need to be stored for shorter or longer periods of time, with dedicated storage requirements to be met. Here, we will uncover these requirements, along with solutions to fulfill them.

RoSS.FILL - single use filling machine for CGT bags

Biomanufacturing: Process, steps and challenges in manufacturing biologics

As biologics have become a central pillar in today’s healthcare sector, their manufacturing process increasingly draws attention. In this article, we will discuss the process step by step, including challenges and possible ways to overcome them.

Bulk drug substance management by Single Use Support

Bulk drug substance management

The following article aims to take a closer look at the term “bulk drug substance” and its meaning, as well as to investigate smart solutions to shorten the phase between development and blockbuster production. Read more about the solution for the biopharmaceutical industry!

  1. What are "Biologics" Questions and Answers, https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/what-are-biologics-questions-and-answers , Published 02.2018
  2. Biologicals, https://www.who.int/health-topics/biologicals#tab=tab_1, Published
  3. Progress in biopharmaceutical development, http://dx.doi.org/10.1002/bab.1617, Published 2017-10-03
  4. Biopharmaceuticals, https://www.sciencedirect.com/topics/medicine-and-dentistry/biopharmaceuticals, Published 2023
  5. What Are "Biologics" Questions and Answers, https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/what-are-biologics-questions-and-answers, Published
  6. HUMIRA® (adalimumab) injection, for subcutaneous use., https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125057s410lbl.pdf, Published
  7. REMICADE (infliximab) Label - accessdata.fda.gov., https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103772s5359lbl.pdf, Published
  8. Enbrel (etanercept) Label - accessdata.fda.gov, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/103795s5591lbl.pdf, Published
  9. , Published 1970-01-01
  10. Biologics for RA and Other Autoimmune Conditions, https://www.arthritis-health.com/treatment/medications/biologics-ra-and-other-autoimmune-conditions, Published 10.2016
micheal-eder

Michael Eder

Senior Marketing Manager

Michael Eder, MA, is Senior Marketing Manager at Single Use Support. He is expert in pharma and health communication with his 8+ years experience in pharma. After completing his master's degree in International Healthcare Management at MCI The Entrepreneurial school in Innsbruck, he has gained experience in the pharmaceutical field. Michael creates articles about Freeze Thaw applications and Platform solutions from Single Use Support and is the author of current news with Single Use Support worldwide. 

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