To answer this question, it is first necessary to understand that the medications we use generally come from three basic sources. They are described below:

1. Biological Extracts

Medications produced from extracts, typically from plants, are among the earliest types of medicine used by humanity. A modern example is cannabidiol (CBD), extracted from hemp (Cannabis sativa). Another is vinblastine, used in cancer treatments and derived from the Madagascar periwinkle (Catharanthus roseus). Additionally, willow bark (Salix spp.) is a natural source of salicin, an anti-inflammatory compound that the human body converts into salicylic acid—a precursor to aspirin.

2. Chemical Synthesis

Aspirin (acetylsalicylic acid) is a prime example of a drug obtained through this method. While salicin was used as a medicine derived from willow bark, aspirin itself is produced via chemical synthesis. Salicylic acid is chemically manufactured through the Kolbe-Schmitt reaction, which treats sodium phenoxide with carbon dioxide ($CO_2$) under high pressure and temperature, followed by acidification. The resulting salicylic acid is then used to synthesize acetylsalicylic acid through acylation with acetic anhydride.

3. Biopharmaceuticals (Biologics)

Unlike synthetic chemicals, biopharmaceuticals are drugs produced from living organisms (such as cells, bacteria, and yeast) or biological materials (including proteins, RNAs, and enzymes) using advanced biotechnology. These are complex molecules—such as monoclonal antibodies, recombinant proteins, RNAs, and vaccines—used to treat chronic diseases, autoimmune disorders, and cancer by acting on specific targets within the body.

Biologics are derived from the genetic manipulation of organisms to enable the production of proteins of biomedical interest, such as insulin, growth hormones, antibodies, and growth factors produced in Escherichia coli bacteria or cultured mammalian cells. In these cases, the bacteria are genetically engineered to produce the biological product using a cloned human gene inserted into the cell. Beyond bacteria, scientists can also engineer insect cells, mammalian cells, plant cells, and even organisms such as cattle, sheep, fish, and plants.

The mRNA vaccines used to combat COVID-19 are biological products obtained through enzymatic synthesis. This process uses recombinant RNA polymerase enzymes (derived from E. coli) and a cloned DNA template to transcribe the mRNA. This mRNA is then encapsulated in lipid nanoparticles to create the final vaccine formulation.

When used correctly, all medications are safe and essential for people's health and quality of life. Drugs undergo rigorous testing before being approved and must be regulated by official health agencies. In Brazil, this role is expertly fulfilled by the National Health Surveillance Agency (Anvisa). Instituto Butantan is a global benchmark in the production of immunobiologicals and, through CeRDI, works to create even more advanced and efficient biopharmaceuticals, specifically focusing on monoclonal antibodies and influenza vaccines

Before being approved for public use, every medication—including vaccines and monoclonal antibodies—undergoes rigorous testing. The goal is to ensure they are not only effective in fighting disease but also safe. All medications can cause side effects and must be used with care. Nevertheless, testing usually demonstrates that the benefits outweigh any adverse effects, allowing the drug to be approved with specific guidelines and warnings regarding potential risks.

But how do these tests work? While animal testing and trials involving human volunteers (usually healthy individuals) are well-known, patients already facing a specific health condition often volunteer to participate in the development of new treatments. All these methods can be part of the same study, which is generally divided into two main types: non-clinical and clinical trials.

Non-clinical Trials

Essentially, these are tests that do not involve human subjects and typically represent the first phase of developing a new drug. Non-clinical trials have two goals: first, to verify if the active ingredient effectively hits the target causing the disease; and second, to identify if any substances in the medication could be toxic or cause adverse reactions over time. If a new substance fails this stage, there is no reason to proceed with human testing.

Animal testing is very common in non-clinical studies: mice are the most well-known subjects, but monkeys and even dogs can help researchers discover how a new drug behaves. However, there are other forms of non-clinical testing, such as in vitro studies (using cells or tissue samples grown in a laboratory) and computer modeling (using data-driven calculations and virtual simulations).

Clinical Trials

Once non-clinical trials yield promising results, clinical trials in humans may be approved. In this stage, the new substance is tested in different ways depending on the health issue being studied. Research usually begins with a small group of healthy volunteers to map risks and side effects. Next, patients with the disease are included to evaluate efficacy, although safety is continuously monitored throughout all clinical trials. Adults from high-risk groups may also be included later.

Often, the mere expectation of improvement from a new substance can make a patient feel better—this is known as the placebo effect. Researchers must ensure that the medication works beyond this psychological effect. This is why blind trials are common: patients are divided into two groups; one receives the experimental drug and the other receives a placebo, but no patient knows which group they are in. There are also double-blind trials, where neither the patients nor the doctors administering the substance know who is receiving the real medication and who is receiving the placebo. This ensures that researchers interpret the data without being influenced by their own desire for the drug to succeed. The approval process for a new medication involves three primary clinical phases. Phase 1: Conducted with a small group (10–20 individuals) to primarily evaluate safety; Phase 2: Conducted with a larger group (100–200 individuals) to assess efficacy while continuing safety evaluations; Phase 3: Conducted with thousands of individuals to primarily evaluate efficacy on a large scale, while safety remains under constant monitoring.

After Phase 3 approval, the medication can be registered and produced. There is also Phase 4, consisting of post-marketing clinical trials where efficacy and safety are monitored while the product is already commercially available. Throughout all these stages, Pharmacovigilance tracks all short- and long-term adverse effects as well as ongoing effectiveness. Even after approval and distribution, medications continue to be studied long-term. Understanding and valuing every stage of this life-saving research is essential. The Center for Research and Development in Immunobiologicals (CeRDI) conducts clinical trials to ensure the efficacy and safety of the innovative influenza vaccines and monoclonal antibodies developed by Instituto Butantan, enabling their registration, manufacturing, and use by the population.

To understand these diseases, we must first review how the immune system functions. Leukocytes are cells that circulate in the blood and work to defend the body. Also known as white blood cells, there are five main types: neutrophils, monocytes, eosinophils, basophils, and lymphocytes. With the exception of lymphocytes, these cell types participate in the innate immune response, which represents the body's first line of non-specific defense. Lymphocytes, on the other hand, are divided into two primary types: T lymphocytes (T cells) and B lymphocytes (B cells). These two types participate in the adaptive immune response. B cells specialize in recognizing and fighting invaders by producing antibodies—either secreted into the bloodstream or bound to the cell membrane—while T cells are responsible for the cell-mediated immune response.

Any microorganism foreign to the body that can cause disease is called a pathogen. Every pathogen carries antigens on its surface that serve as targets for the immune system. These antigens have specific, identifiable markers known as epitopes, which are recognized by antibodies. B lymphocytes produce immunoglobulins; when these proteins are secreted, they circulate in the blood, recognize the epitopes on antigens, and, in most cases, neutralize the pathogen.

However, lymphocytes can sometimes make a mistake: they may confuse the body's own healthy cells with foreign invaders. When this happens, the immune system attacks the person's own cells, tissues, and organs—these are known as autoimmune diseases.With biopharmaceuticals such as monoclonal antibodies, it is possible to modulate the immune response of these lymphocytes, creating a more appropriate "immune memory" that can be either immunosuppressive or immunostimulatory. This is one of the vital areas of research developed by the Center for Research and Development in Immunobiologicals (CeRDI).

Hyperimmune sera are a type of immunobiological medication used in various treatments and can be of human or animal origin. They are produced by purifying antibodies from immunocompetent people (with an immune system capable of defending the organism), immunized individuals, or animals immunized against specific antigens. The sera work to boost the body's natural defense system or fight an active infection or risk of infection.

For example, individuals vaccinated against the tetanus antigen have a high antibody titer and can have their blood collected and immunoglobulins purified from their plasma. The final product will be hyperimmune serum against the tetanus antigen, used in the treatment of individuals presenting with tetanus. The same occurs with individuals who receive the rabies vaccine, for example. Thus, human hyperimmune sera (called homologous) are produced against specific infections.

Similarly, this process can be used to produce hyperimmune sera in animals. Instituto Butantan produces several types of antivenom sera with the help of horses: the antibodies are obtained from the blood plasma of animals immunized with mixtures of snake venoms. These equine sera are used in the therapy of individuals who have been bitten by the snakes for which the sera were produced.

Heterologous hyperimmune sera (produced from horse plasma) and homologous hyperimmune sera (produced from human plasma) contain polyclonal immunoglobulins—that is, immunoglobulins that recognize diverse epitopes or distinct antigens, depending on the immunizing agent used. Instituto Butantan produces 12 types of horse hyperimmune sera for treatments of accidents involving snakes, scorpions, spiders, Lonomia caterpillars, rabies virus infection, tetanus, diphtheria, and botulism.

Treatment with hyperimmune sera is safe; however, like any medication, they have their limitations. Some patients may have mild allergic reactions, or develop resistance and a reaction with repeated use of equine sera—resulting in the individual producing antibodies against the horse's immunoglobulins.

Monoclonal antibodies

B lymphocytes are responsible for producing antibodies. Each lymphocyte produces a single, unique type of immunoglobulin, which we call monoclonal. A polyclonal hyperimmune serum is a mixture of distinct types of immunoglobulins specialized in neutralizing different epitopes and antigens, produced by different B lymphocytes; a monoclonal antibody, on the other hand, is produced by a single B lymphocyte that, once expanded, produces a population of clones of the originally generated B lymphocyte, with all of them producing the exact same immunoglobulin molecule.

Initially, murine monoclonal antibodies (derived from mice) were produced for therapeutic use. However, they were recognized by the patient's immune system as non-human, and with repeated use, the patient's body produced antibodies against these murine monoclonals. Next, these antibodies were humanized using genetic engineering, but they still contained portions of murine immunoglobulin.

Therapeutic performance improved in clinical practice, but even so, these antibodies were still recognized by the patient's immune system. To solve this problem, it was necessary to clone the full sequences of human immunoglobulins to express human monoclonal antibodies in cells using genetic engineering techniques, employing animal cell lines such as the CHO cell line (Chinese hamster ovary cells).

Vaccines, hyperimmune sera, and monoclonal antibodies are the most well-known immunobiological medications, and they work to increase the immune system's defensive capacity through specific antibodies. In general, vaccines induce an immune response—mainly antibody production—that serves to prevent the vaccinated individual from contracting the infection against which the vaccine was administered. Hyperimmune sera, on the other hand, serve to treat an infection that is already established or in the process of becoming established.

There are different technologies for producing vaccines, each with its own advantages. But the principle of every vaccine is the same: to teach the immune system, particularly B lymphocytes, how to produce the right immunoglobulins to identify and capture a pathogen even before it enters the body. In addition to protecting the person who received the immunizing agent, vaccines—when used in mass vaccination programs—protect the entire population. Even unvaccinated individuals can be protected when vaccination coverage is high, through the so-called herd effect: with a large number of immunized individuals, the infection cannot establish itself in the population, preventing it from reaching the few who have not yet received the vaccine. For this reason, high vaccination coverage is important.

Today, many diseases are considered globally or regionally eradicated thanks to vaccines. Thus, vaccination induces an active immune response through the production of antibodies as well as a specific cellular response. In some special cases where infection is a very slow process, vaccination can induce an immune response that prevents the disease even when the pathogen is already active in the body—as is the case with the rabies virus, for example. In this case, there is a therapeutic immunization protocol known as a post-exposure protocol.

Hyperimmune sera, on the other hand, are prepared with purified immunoglobulins from previously vaccinated individuals (homologous sera) or vaccinated animals (heterologous sera) used to treat infected individuals. Their production basically consists of extracting antibodies from the blood of a person or animal that has already been vaccinated. They can also be obtained from individuals who contracted the disease but recovered (this technique is less common). Hyperimmune sera can also be used in cases of envenomation by venomous animals (through bites, stings, or other accidents), such as the antivenom sera produced by Instituto Butantan.

Homologous or heterologous hyperimmune sera are composed of antibody populations that recognize distinct antigens or antigenic determinants (epitopes), produced by distinct populations of B lymphocytes. Vaccination is considered an active process because it leads to the activation of the immune system and antibody production, whereas the use of hyperimmune serum is considered a passive process, using previously produced and purified antibodies that are introduced into the individual under treatment.

Monoclonal antibody therapy is very similar to hyperimmune serum therapy because the therapeutic principle is the same: a passive immunization process. However, the most common sera use polyclonal antibodies (produced by different clones of the B-lymphocyte population; each clone produces a molecule with a unique immunoglobulin structure), whereas monoclonal antibodies contain only antibody molecules with a single molecular structure. That is, all antibodies are identical and have an identical chemical structure because they are derived from a single B-lymphocyte clone. Monoclonal antibodies can be of animal origin, humanized, human, or obtained through genetic engineering in the form of ScFvs (single-chain variable fragments).

Thus, biotechnology research has enabled increasingly precise immunizing agents to be available to more people in a shorter development timeframe. For this reason, the work of the Center for Research and Development of Immunobiologicals (CeRDI) is important, developing projects on two main fronts: improving vaccines against various types of influenza viruses, and treating infectious diseases with monoclonal antibodies.

A special type of biological medication that has been a success in treating various diseases and is one of the most important focal points of work at the Center for Research and Development in Immunobiologicals (CeRDI). Monoclonal antibodies are defense proteins produced by B lymphocytes or plasma cells (derived from activated B lymphocytes that transform into plasma cells) from a single cell, cell line, or clones, in order to produce a single molecular form of the antibody to identify and bind to specific targets.

Normally, during an infection, lymphocytes as a whole produce a wide variety of antibodies against the pathogen. Each lymphocyte lineage, or clone, is responsible for producing one type of antibody that makes up this huge variety. Several monoclonal antibodies, which recognize various specific targets, as a whole end up forming polyclonal antibodies—that is, produced by various clones and cell types of B lymphocytes or plasma cells. Monoclonal antibodies, on the other hand, offer advantages in certain treatments: it is possible to selectively inhibit enzymes, proteins, receptors, and targets, therapeutically interfering with the core mechanism of a disease.

Monoclonal antibodies can be produced through hybridoma techniques, clone selection, monoclonal production and purification, or through genetic engineering using structural information from the antibody of interest. Monoclonal antibodies are also part of the body's natural defense mechanisms against infections and can also be produced against specific proteins and targets to be used in therapies such as against rheumatoid arthritis, cancer, and other problems caused by tumors.