What is a biological product?

Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting-edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.

How do biological products differ from conventional drugs?

In contrast to most drugs that are chemically synthesized and their structure is known, most biologics are complex mixtures that are not easily identified or characterized. Biological products, including those manufactured by biotechnology, tend to be heat sensitive and susceptible to microbial contamination. Therefore, it is necessary to use aseptic principles from initial manufacturing steps, which is also in contrast to most conventional drugs.

Biological products often represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available.

Biological therapy involves the use of biologically derived agents to modify the relationship between tumor and host, altering the host's biologic response to tumor cells, with a resultant therapeutic effect. Most biological therapies are designed to activate the patient's immune system and induce it to attack cancer cells. Common biological agents that have been approved for use in treating specific types of cancer are described below. Some of these are still under investigation.

Interferons

Interferons are proteins secreted by immune cells that interfere with a virus's ability to reproduce and proliferate. The human body produces interferons as part of the immune response. The name comes from the fact that they literally interfere with virus replication.

Through recombinant DNA technology, various interferons have been genetically engineered for use in the medical treatment of disease. These agents increase the cell-killing activity of the immune system, making tumor cells more vulnerable to immune attack by increasing antigens and blocking the formation of new blood vessels by tumors. They also slow tumor cell replication by inhibiting DNA and protein synthesis.

There are three known classes of interferons: alpha-, beta-, and gamma-interferons. Only alpha-interferon has been approved as a cancer treatment. For example, inteferon alfa-2b (Intron A) is used in conjunction with chemotherapy in patients with follicular lymphoma and has proven to be effective for treating malignant melanoma.

Monoclonal antibodies (MABs)

Monoclonal antibodies are lab-engineered products. They are components of the immune system which are able to recognize and bind to a specific antigen. These lab-made antibodies are designed to react directly against certain tumor-associated proteins. They may be used by themselves or equipped with other molecules, such as toxins, chemotherapy drugs, or radioactive isotopes.

Although MABs hold great potential for cancer treatment, complete success has been elusive.

The only monoclonal antibodies available for routine use are for lymphomas, some types of breast cancer, and occasionally for bladder cancer. The early results of treatment with these therapeutic monoclonal antibodies have been quite promising. Sometimes they have been given on their own, but more commonly in combination with conventional chemotherapy.

Interleukins

Interleukin (abbreviated IL) is a group of bioactive proteins produced by leukocytes, monocytes, and other cells that regulate the immune response. They act like messengers between the white blood cells of the immune system. Interleukin-2 increases the activity of lymphocytes, especially killer T-cells. Recombinant IL-2 is used for cancer therapy and continues to be studied as a biological therapy agent for other diseases.

Growth factors are colony stimulating factors or hematopoietic growth factors. These substances promote the growth and maturation of normal cells. There are two types used in cancer treatment: one type stimulates bone marrow to make normal cells; the other acts as an anticancer agent. Colony stimulating factors are being used increasingly in the treatment of bone marrow transplant patients. They are also used for patients who develop anemia or low white blood cell counts because of cancer or cancer therapy.

Tumor vaccines

Vaccines against viral disease are effective in preventing human infections. They are administered to prevent infections for which effective treatments are not available, especially when active infection is associated with high mortality.

Tumor vaccines are a type of immunotherapy that attempt to stimulate the patient's own immune system to respond to tumor antigens. Melanoma vaccines have been administered to patients for several decades in hopes of boosting immunity to the patient's melanoma, usually as an adjuvant to surgery. Tumor vaccines are still experimental.

With further research and more secrets about the immune system revealed, the prospect of biological therapies looks promising and hopefully the role of biological therapies in the successful treatment of cancer will grow in future years.

The U.S. Food and Drug Administration has approved biosimilar medications to treat conditions such as cancer, diabetes, Crohn’s disease, colitis, rheumatoid arthritis, psoriasis, and more.

But what are biosimilar and interchangeable biosimilar biological medications? To answer that question, it helps to first know what biological products (biologics) are.

Biologics: Medications from Living Organisms

Biologics include medicines that generally come from living organisms, which can include animal cells and microorganisms, such as yeast and bacteria. That makes biologics different from conventional medications, which are commonly made from chemicals.

Unlike conventional medications, biologics generally cannot be made by following a chemical “recipe.” Because biologics generally come from living organisms, their nature varies, and their structures are generally more complex. Thus, developing biologics can be a more complicated process than manufacturing conventional drugs.

A biosimilar is a biologic that is highly similar to, and has no clinically meaningful differences from, another biologic that’s already FDA-approved (referred to as the reference product or original biologic). This means biosimilars:

• Are given the same way (same route of administration).
• Have the same strength and dosage form.
• Have the same potential side effects.

Biosimilars provide the same potential treatment benefits as the original biologic and are generally made with the same types of natural sources as the reference product.

Biosimilars Are Safe and Effective

Biosimilars are as safe and effective as the original biologic; both are rigorously and thoroughly evaluated by the FDA before approval. Before approving a biosimilar, FDA experts must conclude it is highly similar to and has no clinically meaningful differences from the original biologic. The FDA’s thorough evaluation ensures that all biosimilar products are as safe and effective as their reference products and meet the FDA’s high standards for approval. This means you can expect the same safety and effectiveness from the biosimilar over the course of treatment as you would from the original product.

In addition, the FDA closely regulates the manufacturing of biosimilars. The same quality manufacturing standards that apply to the original biologic also apply to the biosimilar. It must be manufactured in accordance with Current Good Manufacturing Practice requirements, which cover:

• Methods.
• Facilities.
• Controls for the manufacturing, processing, packaging, or holding of a drug product.

This helps to prevent manufacturing mistakes or unacceptable impurities and to ensure consistent product quality.

Interchangeable Biosimilar Medications

An interchangeable biosimilar product is a biosimilar that meets additional requirements outlined by the law that allows for the FDA to approve biosimilar and interchangeable biosimilar medications.

An interchangeable biosimilar product may be substituted without the intervention of the health care professional who prescribed the reference product, much like how generic drugs are routinely substituted for brand name drugs. This is commonly called pharmacy-level substitution and is subject to state pharmacy laws.

A health care provider also can prescribe an interchangeable biosimilar product just like they would prescribe a biosimilar or a reference product. Because of the FDA’s high standards for approval, health care providers and patients can be confident in the safety and effectiveness of a biosimilar or an interchangeable biosimilar product, just as they would be for the FDA-approved original product.

Biologics are among the fastest growing segments of the prescription product market. The FDA approval of additional biosimilar and interchangeable biosimilar medications may help stimulate competition. Patients will have more treatment options and potentially less expensive alternatives.

You can search the Purple Book database for information about biological products, including biosimilar and interchangeable biosimilar products, approved by the FDA.

Researchers hope stem cells will one day be effective in the treatment of many medical conditions and diseases. But unproven stem cell treatments can be unsafe—so get all of the facts if you’re considering any treatment.

Stem cells have been called everything from cure-alls to miracle treatments. But don’t believe the hype. Some unscrupulous providers offer stem cell products that are both unapproved and unproven. So beware of potentially dangerous procedures—and confirm what’s really being offered before you consider any treatment.

The facts: Stem cell therapies may offer the potential to treat diseases or conditions for which few treatments exist. Sometimes called the body’s “master cells,” stem cells are the cells that develop into blood, brain, bones, and all of the body’s organs. They have the potential to repair, restore, replace, and regenerate cells, and could possibly be used to treat many medical conditions and diseases.

But the U.S. Food and Drug Administration is concerned that some patients seeking cures and remedies are vulnerable to stem cell treatments that are illegal and potentially harmful. And the FDA is increasing its oversight and enforcement to protect people from dishonest and unscrupulous stem cell clinics, while continuing to encourage innovation so that the medical industry can properly harness the potential of stem cell products.

To do your part to stay safe, make sure that any stem cell treatment you are considering is either:

• FDA-approved, or;
• Being studied under an Investigational New Drug Application (IND), which is a clinical investigation plan submitted and allowed to proceed by the FDA.

Stem Cell Uses and FDA Regulation

The FDA has the authority to regulate stem cell products in the United States.

Today, doctors routinely use stem cells that come from bone marrow or blood in transplant procedures to treat patients with cancer and disorders of the blood and immune system.

With limited exceptions, investigational products must also go through a thorough FDA review process as investigators prepare to determine the safety and effectiveness of products in well-controlled human studies, called clinical trials. The FDA has reviewed many stem cell products for use in these studies.

As part of the FDA’s review, investigators must show how each product will be manufactured so the FDA can make sure appropriate steps are being taken to help assure the product’s safety, purity, and strength (potency). The FDA also requires sufficient data from animal studies to help evaluate any potential risks associated with product use. (You can learn more about clinical trials on the FDA’s website.)

That said, some clinics may inappropriately advertise stem cell clinical trials without submitting an IND. Some clinics also may falsely advertise that FDA review and approval of the stem cell therapy is unnecessary. But when clinical trials are not conducted under an IND, it means that the FDA has not reviewed the experimental therapy to help make sure it is reasonably safe. So be cautious about these treatments.

About FDA-approved Products Derived from Stem Cells

The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.

These products are approved for limited use in patients with disorders that affect the body system that is involved in the production of blood (called the “hematopoietic” system). These FDA-approved stem cell products are listed on the FDA website. Bone marrow also is used for these treatments but is generally not regulated by the FDA for this use.

Safety Concerns for Unproven Stem Cell Treatments

All medical treatments have benefits and risks. But unproven stem cell therapies can be particularly unsafe.

For instance, attendees at a 2016 FDA public workshop discussed several cases of severe adverse events. One patient became blind due to an injection of stem cells into the eye. Another patient received a spinal cord injection that caused the growth of a spinal tumor.

Other potential safety concerns for unproven treatments include:

• Administration site reactions,
• The ability of cells to move from placement sites and change into inappropriate cell types or multiply,
• Failure of cells to work as expected, and
• The growth of tumors.

Note: Even if stem cells are your own cells, there are still safety risks such as those noted above. In addition, if cells are manipulated after removal, there is a risk of contamination of the cells.

Advice for People Considering Stem Cell Therapies

Know that the FDA plays a role in stem cell treatment oversight. You may be told that because these are your cells, the FDA does not need to review or approve the treatment. That is not true.

Stem cell products have the potential to treat many medical conditions and diseases. But for almost all of these products, it is not yet known whether the product has any benefit—or if the product is safe to use.

If you're considering treatment in the United States:

• Ask if the FDA has reviewed the treatment. Ask your health care provider to confirm this information. You also can ask the clinical investigator to give you the FDA-issued Investigational New Drug Application number and the chance to review the FDA communication acknowledging the IND. Ask for this information before getting treatment—even if the stem cells are your own.
• Request the facts and ask questions if you don’t understand. To participate in a clinical trial that requires an IND application, you must sign a consent form that explains the experimental procedure. The consent form also identifies the Institutional Review Board (IRB) that assures the protection of the rights and welfare of human subjects. Make sure you understand the entire process and known risks before you sign. You also can ask the study sponsor for the clinical investigator’s brochure, which includes a short description of the product and information about its safety and effectiveness.

If you're considering treatment in another country:

• Learn about regulations that cover products in that country.
• Know that the FDA does not have oversight of treatments done in other countries. The FDA typically has little information about foreign establishments or their stem cell products.
• Be cautious. If you’re considering a stem cell-based product in a country that may not require regulatory review of clinical studies, it may be hard to know if the experimental treatment is reasonably safe.

Blood stem cell transplants can be life-saving for people with a number of conditions. However, it can be challenging to find blood stem cells in needed quantities from a donor whose cells are similar enough to a patient’s cells to be a sufficient “match” for transplantation. Cells from bone marrow and from circulating blood have been used in treatments for many years, and blood from the umbilical cord, collected after a baby is born, has been another source of blood stem cells used more recently. Cord blood from donors is available in public cord blood “banks,” and the match between donor and recipient may not need to be quite as close as is needed for transplants of other types of blood cells. However, cord blood from each donor exists in only limited quantities. Researchers supported by NIDDK have discovered key factors that promote blood stem cell growth and maturation, and, with these insights, have developed ways to expand the numbers of cells from cord blood for use in transplants. This research may increase the availability of such treatments to benefit many more people.

Cord Blood Cell Transplantation

Cord blood is found in blood vessels of the placenta and the umbilical cord—tissue that is normally discarded. It is collected after a baby is born and after the umbilical cord is cut between the mother and the baby. Approved by the U.S. Food and Drug Administration only for use in blood (hematopoietic) stem cell transplantation procedures, cord blood has been transplanted into thousands of patients who have serious medical conditions such as bone marrow failure syndromes, blood disorders, immunodeficiencies, certain metabolic disorders, and cancers. Cord blood stem cells (which are different from embryonic stem cells) facilitate healing and repair of damaged cells and tissue—that is, they are early stage blood cells that, like other blood stem cells, provide a source for the regrowth of all the types of specialized blood cells. Cord blood transplantation, therefore, is an example of regenerative medicine.

A critical advantage of cord blood is that cord blood stem cells can be easily transplanted; the transplanted cells do not have to be an exact match with the recipient’s tissues. However, the main disadvantage is that a single umbilical cord is insufficient; a single umbilical cord contains a limited number of stem cells that do not mature into a sufficient number of specialized types of blood cells needed for adults. Cord blood cell transplants (from a single umbilical cord) could thus place an adult patient at increased risk of life-threatening infections due to the inadequate number of infection-fighting types of blood cells. Such patients may need two or more units of cord blood. Yet, they may still be at risk because, compared with conventional bone marrow transplantation, it may take longer for transplanted cord blood stem cells to engraft—that is, to start working properly in a patient’s body—and give rise to other types of blood cells. For this reason, cord blood cell treatment is used more often in children, who have a small body size and thus require fewer cells. Basic research on blood cells has sparked ideas for expanding the numbers of cells in a unit of cord blood.

Notch: The Story Begins

In 1994, while investigating the cellular and molecular mechanisms underlying the production and function of blood cells—NIDDK-supported researchers discovered for the first time that in human early stage blood cells, a gene encoding a protein called Notch is “turned on.” NIDDK-supported researchers then set out to determine whether Notch influences the function of blood stem cells. Notch, which sits in the cell membrane, transmits signals originating from the outside of the cell to direct the turning on or turning off of genes. Using laboratory mice, they demonstrated, in 2002, that activated Notch had two distinct activities—1) the inhibition of stem cell maturation into different blood cell types and 2) the stimulation of stem cell self-renewal (i.e., an increase in stem cell number). In 2003, with support from NIDDK and other sources, researchers reported that they could induce early stage mouse blood cells to proliferate by exposing the cells to an engineered protein that binds to Notch; this protein was a modified version of a protein called Delta1. Interestingly, the researchers did not see this effect if they simply mixed the modified Delta1 protein into the liquid in which the cells were growing; through their experiments, they realized they had to immobilize this protein on the dish in which the cells were growing for it to have the desired effect of increasing the numbers of cells.

Notch-driven Engraftment of Cord Blood Cells in Human Pilot Study

Taking advantage of their knowledge of the Notch-signaling pathway and blood stem cells and the modified Delta1 protein, investigators supported by NIDDK and others were able to significantly increase, by greater than 100-fold, the number of early stage blood cells from a unit of cord blood. The researchers then conducted, and reported in 2010, a pilot clinical study of 10 participants with leukemia to begin to assess the safety of infusing patients with cord blood stem cells that had been expanded to greater numbers using the modified Delta1 protein/Notch procedure, and to begin evaluating the engraftment properties of the expanded stem cells. In the course of their treatment for leukemia, the participants were given radiation therapy and chemotherapy to destroy the blood cancer cells; these treatments also destroyed the stem cells in their bone marrow. Cord blood cell transplantation was subsequently used to repopulate the bone marrow. Each participant received two units of cord blood—one unit of non-expanded blood and one containing expanded numbers of blood cells, or two units of non-expanded blood. In this small group of participants, no safety issues were encountered. In addition, the time for engraftment, measured in terms of white blood cell recovery, was significantly shorter for participants who received Delta1/Notch-expanded cells than for those who received only non-expanded cord blood.

Manipulating Blood Stem Cells into Mature Blood Cells

Blood stem cells mature along two tracks—1) the myeloid lineage, which produces white blood cells (e.g., macrophages and neutrophils), red blood cells, and other cells, and 2) the lymphoid lineage, which produces T cells, B cells, and other cells. The immune system consists of two major pillars: the innate (general defense) and the adaptive (specialized defense). Both systems work closely together and take on different tasks. Researchers have sought to identify a minimum cocktail of factors necessary to enable the reconstitution of both myeloid and lymphoid lineages from blood stem cells. Previous NIH-supported research found that experimentally increasing production of a factor called HoxB4 in mouse early stage blood stem cells could reconstitute the myeloid lineage but only minimally reconstituted the lymphoid lineage. In further experiments to try to reconstitute both lineages, in 2016, investigators supported by NIDDK and others discovered that Delta1/Notch activation of mouse early stage blood stem cells, in combination with increased HoxB4 in these cells, enabled the cells to fully reconstitute the myeloid and lymphoid lineages when transplanted into mice lacking their own blood cells.

A relatively new approach for cancer treatment is biological therapy. This cancer treatment is also known as biotherapy, immunotherapy, or biological response modifier therapy.

Biological therapy began with the discovery of immunization more than 200 years ago. Edward Jenner discovered the benefits of injecting humans with fluid taken from sores on cattle infected with cowpox, a disease also known as vaccinia. This fluid contains the organisms that produce the disease. His inoculation worked because the cells of the immune system developed antibodies against the cowpox organism.

About a century later, William Coley, a New York surgeon, started using biological therapy to treat cancer patients. He noticed that people with some kinds of cancer appeared to enter remission after developing certain bacterial infections. He concluded that the body's response to the infection must be exerting some effect on the cancer. He injected cancer patients with live bacteria, then later with filtered toxins. This induced an infectious response that sometimes led to a remission of their cancer. This method of treatment became known as Coley's toxins and was used for decades.

Paul Ehrlich, a German Nobel Prize winner in 1908, theorized that the surfaces of cells carried receptor molecules, or side chains as he called them. He pointed out that antibodies attached to these "side chains" triggered the release of antitoxins. He also believed that antibodies might be developed that could target invaders.

In the mid-1980s, encouraging results were seen in the use of interferon to treat a rare blood disorder called hairy-cell leukemia. The FDA has approved interferon for this disease, as well as chronic myelogenous leukemia, AIDS-related Kaposi's sarcoma, and genital warts.

More recently, Steven Rosenberg, a researcher at the U.S. National Cancer Institute, proved that the human immune system could be directed to discriminate between healthy cells and cancerous ones. Handled properly, immunotherapy could indeed stimulate the body's defenses. In 1992 genetically engineered IL-2 received the FDA's approval for treating advanced kidney cancer. In 1994 clinical trials were started to determine whether another interleukin, interleukin ("IL-12"), might have some benefit against metastatic cancer and AIDS.

To understand biological therapy, it helps to know some basics about the immune system, a complex network of organs and cells.

There are two basic types of defense protecting the body from foreign invaders such as bacteria, viruses, or cancer cells. The first line of defense is a physical barrier involving the skin, mucous membranes, the lining of the respiratory tract. This line of defense produces a nonspecific response because it works regardless of the invader.

The second line of defense, unlike the physical barrier, recognizes these invaders and then develops the specific weapons to fight them. It is even able to remember what the invader looked like so that the next time its response will be even swifter. This line of defense that produces a specific response is made by immune system cells. The immune system cells circulate throughout the body and defend the body against attacks by foreign invaders.

This immune network is one of the body's main defenses against disease. It works against diseases, including cancer, in a variety of ways. For example, the immune system may recognize the difference between healthy cells and cancer cells in the body and work to eliminate those that become cancerous.

Immune system cells include lymphocytes (white blood cells) and other immune cells. Lymphocytes are the most important cells of the immune system and can be categorized into T-cells, B-cells, and NK (Natural Killer) cells.

T-cells directly attack infected, foreign, or cancerous cells. T-cells also regulate the immune response by signaling other immune system defenders. B-cells secrete antibodies, the proteins that recognize and attach to foreign substances known as antigens. Natural Killer cells produce powerful chemical substances that bind to and kill any foreign invader. They attack without first having to recognize a specific antigen. Monocytes are white blood cells that circulate in the bloodstream. When they settle in tissue, the macrophages engulf the invaders and actually digest them.

Understanding how immune system cells exchange messages and finding ways to make these messages clearer and stronger are the goals of research in immunology. Each of these components, and each step in the immune response, represents a potential avenue for the development of a cancer therapy.

Biological therapy research focuses on isolating specific cells of the immune system and their chemical products, then manipulating them in the laboratory to target their activity and control their effects.

In summary, biological therapies use the body's immune system, either directly or indirectly, to fight cancer or to reduce the side effects that may be caused by some cancer treatments.

Vaccines play an important role in keeping us healthy. They protect us from serious and sometimes deadly diseases — like haemophilus influenzae type b (Hib) and measles.

It’s normal to have questions about vaccines. Vaccines.gov works with scientists and doctors to answer your questions and provide the information you need to get vaccinated.

A few helpful terms

As you learn about vaccines and how they protect you, it may be helpful to understand the difference between vaccines, vaccinations, and immunizations.

Vaccine

A vaccine is made from very small amounts of weak or dead germs that can cause diseases — for example, viruses, bacteria, or toxins. It prepares your body to fight the disease faster and more effectively so you won’t get sick.

Example: Children younger than age 13 need 2 doses of the chickenpox vaccine.

Vaccination

Vaccination is the act of getting a vaccine, usually as a shot.

Example: Schedule your tetanus vaccination today.

Immunization

Immunization is the process of becoming immune to (protected against) a disease.

Example: Because of continued and widespread immunization in the United States, it’s rare for Americans to get polio.

Immunization can also mean the process of getting vaccinated. For example, your “immunization schedule,” is the timing of your shots.

There are several different types of vaccines. Each type is designed to teach your immune system how to fight off certain kinds of germs — and the serious diseases they cause.

When scientists create vaccines, they consider:

• How your immune system responds to the germ
• Who needs to be vaccinated against the germ
• The best technology or approach to create the vaccine

Based on a number of these factors, scientists decide which type of vaccine they will make. There are 4 main types of vaccines:

• Live-attenuated vaccines
• Inactivated vaccines
• Subunit, recombinant, polysaccharide, and conjugate vaccines
• Toxoid vaccines

Live-attenuated vaccines

Live vaccines use a weakened (or attenuated) form of the germ that causes a disease.

Because these vaccines are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response. Just 1 or 2 doses of most live vaccines can give you a lifetime of protection against a germ and the disease it causes.

But live vaccines also have some limitations. For example:

• Because they contain a small amount of the weakened live virus, some people should talk to their health care provider before receiving them, such as people with weakened immune systems, long-term health problems, or people who’ve had an organ transplant.
• They need to be kept cool, so they don’t travel well. That means they can’t be used in countries with limited access to refrigerators.

Live vaccines are used to protect against:

• Measles, mumps, rubella (MMR combined vaccine)
• Rotavirus
• Smallpox
• Chickenpox
• Yellow fever

Inactivated vaccines

Inactivated vaccines use the killed version of the germ that causes a disease.

Inactivated vaccines usually don’t provide immunity (protection) that’s as strong as live vaccines. So you may need several doses over time (booster shots) in order to get ongoing immunity against diseases.

Inactivated vaccines are used to protect against:

• Hepatitis A
• Flu (shot only)
• Polio (shot only)
• Rabies

Subunit, recombinant, polysaccharide, and conjugate vaccines

Subunit, recombinant, polysaccharide, and conjugate vaccines use specific pieces of the germ — like its protein, sugar, or capsid (a casing around the germ).

Because these vaccines use only specific pieces of the germ, they give a very strong immune response that’s targeted to key parts of the germ. They can also be used on almost everyone who needs them, including people with weakened immune systems and long-term health problems.

One limitation of these vaccines is that you may need booster shots to get ongoing protection against diseases.

These vaccines are used to protect against:

• Hib (Haemophilus influenzae type b) disease
• Hepatitis B
• HPV (Human papillomavirus)
• Whooping cough (part of the DTaP combined vaccine)
• Pneumococcal disease
• Meningococcal disease
• Shingles

Toxoid vaccines

Toxoid vaccines use a toxin (harmful product) made by the germ that causes a disease. They create immunity to the parts of the germ that cause a disease instead of the germ itself. That means the immune response is targeted to the toxin instead of the whole germ.

Like some other types of vaccines, you may need booster shots to get ongoing protection against diseases.

Toxoid vaccines are used to protect against:

• Diphtheria
• Tetanus

The future of vaccines

Did you know that scientists are still working to create new types of vaccines? Here are 2 exciting examples:

• DNA vaccines are easy and inexpensive to make — and they produce strong, long-term immunity.
• Recombinant vector vaccines (platform-based vaccines) act like a natural infection, so they're especially good at teaching the immune system how to fight germs.

Today’s vaccines use only the ingredients they need to be safe and effective.

Each ingredient in a vaccine serves a specific purpose. For example, vaccine ingredients may:

• Help provide immunity (protection) against a specific disease
• Help keep the vaccine safe and long lasting
• Be used during the production of the vaccine

Ingredients provide immunity

Vaccines include ingredients to help your immune system respond and build immunity to a specific disease. For example:

• Antigens are very small amounts of weak or dead germs that can cause diseases. They help your immune system learn how to fight off infections faster and more effectively. The flu virus is an example of an antigen.
• Adjuvants , which are in some vaccines, are substances that help your immune system respond more strongly to a vaccine. This increases your immunity against the disease. Aluminum is an example of an adjuvant.

Ingredients keep vaccines safe and long lasting

Some ingredients help make sure a vaccine continues to work like it’s supposed to and that it stays free of outside germs and bacteria. For example:

• Preservatives , like thimerosal, protect the vaccine from outside bacteria or fungus. Today, preservatives are usually only used in vials (containers) of vaccines that have more than 1 dose. That’s because every time an individual dose is taken from the vial, it’s possible for harmful germs to get inside. Most vaccines are also available in single-dose vials and do not have preservatives in them.
• Stabilizers , like sugar or gelatin, help the active ingredients in vaccines continue to work while the vaccine is made, stored, and moved. Stabilizers keep the active ingredients in vaccines from changing because of something like a shift in temperature where the vaccine is being stored.

Ingredients are used during the production of vaccines

Some ingredients that are needed to produce the vaccine are no longer needed for the vaccine to work in a person.

These ingredients are taken out after production so only tiny amounts are left in the final product. The very small amounts of these ingredients that remain in the final product aren’t harmful.

Examples of ingredients used in some vaccines include:

• Cell culture (growth) material , like eggs, to help grow the vaccine antigens.
• Inactivating (germ-killing) ingredients , like formaldehyde, to weaken or kill viruses, bacteria, or toxins in the vaccine.
• Antibiotics , like neomycin, to help keep outside germs and bacteria from growing in the vaccine.

Common questions about vaccine ingredients

Learn more about the types of vaccine ingredients and why they’re used from the common questions below.

Can vaccines with thimerosal cause mercury poisoning?

A: No. Thimerosal has a different form of mercury (ethylmercury) than the kind that causes mercury poisoning (methylmercury). It’s safe to use ethylmercury in vaccines because it’s less likely to build up in the body — and because it’s used in very, very small amounts. Even so, most vaccines do not have any thimerosal in them. If you’re concerned about thimerosal or mercury in vaccines, talk with your doctor.

Can people who are allergic to antibiotics get vaccinated?

A: Yes. However, if you have an allergy to antibiotics, it’s a good idea to talk with your doctor about getting vaccinated. But in general, antibiotics that people are most likely to be allergic to — like penicillin — aren’t used in vaccines.

Can people with egg allergies get vaccinated?

A: Yes. People with egg allergies can get any licensed, recommended flu vaccine that’s appropriate for their age. They no longer have to be watched for 30 minutes after getting the vaccine. People who have severe egg allergies should be vaccinated in a medical setting and be supervised by a health care professional who can recognize and manage severe allergic conditions.

Is the formaldehyde used in some vaccines dangerous?

A: No. If formaldehyde is used to help produce a vaccine, only very small amounts are left in the final product. This amount is so small that it’s not dangerous — in fact, there’s actually more formaldehyde found naturally in our bodies than there is in vaccines made with formaldehyde.

Is the aluminum used in some vaccines dangerous?

A: No. Vaccines made with aluminum have only a very small amount of aluminum in them. For decades, vaccines that include aluminum have been tested for safety — these studies have shown that using aluminum in vaccines is safe.

What are vaccines?

Vaccines are injections (shots), liquids, pills, or nasal sprays that you take to teach your body's immune system to recognize and defend against harmful germs. For example, there are vaccines to protect against diseases caused by:

• Viruses, like the ones that cause the flu and COVID-19
• Bacteria, including tetanus, diphtheria, and pertussis

What are the types of vaccines?

There are several types of vaccines:

• Live-attenuated vaccines use a weakened form of the germ.
• Inactivated vaccines use a killed version of the germ.
• Subunit, recombinant, polysaccharide, and conjugate vaccines use only specific pieces of the germ, such as its protein, sugar, or casing.
• Toxoid vaccines that use a toxin (harmful product) made by the germ.
• mRNA vaccines use messenger RNA, which gives your cells instructions for how to make a protein (or piece of a protein) of the germ.
• Viral vector vaccines use genetic material, which gives your cells instructions for making a protein of the germ. These vaccines also contain a different, harmless virus that helps get the genetic material into your cells.

Vaccines work in different ways, but they all spark an immune response. The immune response is the way your body defends itself against substances it sees as foreign or harmful. These substances include germs that can cause disease.

What happens in an immune response?

There are different steps in the immune response:

• When a germ invades, your body sees it as foreign.
• Your immune system helps your body fight off the germ.
• Your immune system also remembers the germ. It will attack the germ if it ever invades again. This "memory" protects you against the disease that the germ causes. This type of protection is called immunity.

What are immunization and vaccination?

Immunization is the process of becoming protected against a disease. But it can also mean the same thing as vaccination, which is getting a vaccine to become protected against a disease.

Why are vaccines important?

Vaccines are important because they protect you against many diseases. These diseases can be very serious. So getting immunity from a vaccine is safer than getting immunity by being sick with the disease. And for a few vaccines, getting vaccinated can actually give you a better immune response than getting the disease would.

But vaccines don't just protect you. They also protect the people around you through community immunity.

What is community immunity?

Community immunity, or herd immunity, is the idea that vaccines can help keep communities healthy.

Normally, germs can travel quickly through a community and make a lot of people sick. If enough people get sick, it can lead to an outbreak. But when enough people are vaccinated against a certain disease, it's harder for that disease to spread to others. This type of protection means that the entire community is less likely to get the disease.

Community immunity is especially important for people who can't get certain vaccines. For example, they may not be able to get a vaccine because they have weakened immune systems. Others may be allergic to certain vaccine ingredients. And newborn babies are too young to get some vaccines. Community immunity can help to protect them all.

Are vaccines safe?

Vaccines are safe. They must go through extensive safety testing and evaluation before they are approved in the United States.

What is a vaccine schedule?

A vaccine, or immunization, schedule lists which vaccines are recommended for different groups of people. It includes who should get the vaccines, how many doses they need, and when they should get them. In the United States, the Centers for Disease Control and Prevention (CDC) publishes the vaccine schedule.

It's important for both children and adults to get their vaccines according to the schedule. Following the schedule allows them to get protection from the diseases at exactly the right time.