Biopharmaceutical

A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy. Biopharmaceuticals can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances, or may be living cells or tissues. They are isolated from living sources—human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine.
Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. The term biologics is often used more restrictively to mean biopharmaceuticals that are produced using recombinant DNA technology.
Some regulatory agencies use the terms biological medicinal products or therapeutic biological product to refer specifically to engineered macromolecular products like protein- and nucleic acid-based drugs, distinguishing them from products like blood, blood components, or vaccines, which are usually extracted directly from a biological source. Biopharmaceutics is pharmaceutics that works with biopharmaceuticals. Biopharmacology is the branch of pharmacology that studies biopharmaceuticals. Specialty drugs, a recent classification of pharmaceuticals, are high-cost drugs that are often biologics. The European Medicines Agency uses the term advanced therapy medicinal products for medicines for human use that are "based on genes, cells, or tissue engineering", including gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and combinations thereof. Within EMA contexts, the term advanced therapies refers specifically to ATMPs, although that term is rather nonspecific outside those contexts.
Gene-based and cellular biologics, for example, often are at the forefront of biomedicine and biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.
Building on the market approvals and sales of recombinant virus-based biopharmaceuticals for veterinary and human medicine, the use of engineered plant viruses has been proposed to enhance crop performance and promote sustainable production.
In some jurisdictions, biologics are regulated via different pathways from other small molecule drugs and medical devices.

Major classes

Extracted from living systems

Some of the oldest forms of biologics are extracted from the bodies of animals, and other humans especially. Important biologics include:

Whole blood and other blood components
Organ transplantation and tissue transplants
Stem-cell therapy
Antibodies for passive immunity
Human reproductive cells
Human breast milk
Fecal microbiota

Some biologics that were previously extracted from animals, such as insulin, are now more commonly produced by recombinant DNA.

Produced by recombinant DNA

Biologics can refer to a wide range of biological products in medicine. However, in most cases, the term is used more restrictively for a class of therapeutics that are produced using biological processes involving recombinant DNA technology. These medications are usually one of three types:

Substances that are identical to the body's key signaling proteins. Examples are the blood-production stimulating protein erythropoetin, or the growth-stimulating hormone named "growth hormone" or biosynthetic human insulin and its analogues.
Monoclonal antibodies. These are similar to the antibodies that the human immune system uses to fight off bacteria and viruses, but they are "custom-designed" and can therefore be made specifically to counteract or block any given substance in the body, or to target any specific cell type; examples of such monoclonal antibodies for use in various diseases are given in the table below.
Receptor constructs, usually based on a naturally occurring receptor linked to the immunoglobulin frame. In this case, the receptor provides the construct with detailed specificity, whereas the immunoglobulin structure imparts stability and other useful features in terms of pharmacology. Some examples are listed in the table below.

Biologics as a class of medications in this narrower sense have had a profound impact on many medical fields, primarily rheumatology and oncology, but also cardiology, dermatology, gastroenterology, neurology, and others. In most of these disciplines, biologics have added major therapeutic options for treating many diseases, including some for which no effective therapies were available, and others where previously existing therapies were inadequate. However, the advent of biologic therapeutics has also raised complex regulatory issues, and significant pharmacoeconomic concerns because the cost for biologic therapies has been dramatically higher than for conventional medications. This factor has been particularly relevant since many biological medications are used to treat chronic diseases, such as rheumatoid arthritis or inflammatory bowel disease, or for the treatment of otherwise untreatable cancer during the remainder of life. The cost of treatment with a typical monoclonal antibody therapy for relatively common indications is generally in the range of €7,000–14,000 per patient per year.
Older patients who receive biologic therapy for diseases such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis are at increased risk for life-threatening infection, adverse cardiovascular events, and malignancy.
The first such substance approved for therapeutic use was biosynthetic "human" insulin made via recombinant DNA. Sometimes referred to as rHI, under the trade name Humulin, was developed by Genentech, but licensed to Eli Lilly and Company, who manufactured and marketed it starting in 1982.
Major kinds of biopharmaceuticals include:

Blood factors
Thrombolytic agents
Hormones
Haematopoietic growth factors
Interferons
Interleukin-based products
Vaccines
Monoclonal antibodies
Additional products

Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2 billion in 2008. A few examples of biologics made with recombinant DNA technology include:

USAN/INN	Trade name	Indication	Technology	Mechanism of action
abatacept	Orencia	rheumatoid arthritis	immunoglobin CTLA-4 fusion protein	T-cell deactivation
adalimumab	Humira	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease	monoclonal antibody	TNF antagonist
alefacept	Amevive	chronic plaque psoriasis	immunoglobin G1 fusion protein	incompletely characterized
erythropoietin	Epogen	anemia arising from cancer chemotherapy, chronic renal failure, etc.	recombinant protein	stimulation of red blood cell production
etanercept	Enbrel	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis	recombinant human TNF-receptor fusion protein	TNF antagonist
infliximab	Remicade	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease	monoclonal antibody	TNF antagonist
trastuzumab	Herceptin	breast cancer	humanized monoclonal antibody	HER2/neu antagonist
ustekinumab	Stelara	psoriatic arthritis, psoriasis, ulcerative colitis, Crohn's disease	humanized monoclonal antibody	IL-12 and IL-23 antagonist
denileukin diftitox	Ontak	cutaneous T-cell lymphoma	Diphtheria toxin engineered protein combining Interleukin-2 and Diphtheria toxin	Interleukin-2 receptor binder
golimumab	Simponi	rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis	monoclonal antibody	TNF antagonist
vedolizumab	Entyvio	ulcerative colitis, Crohn's disease	monoclonal antibody	α₄β₇ integrin blocker
ixekizumab	Taltz	plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis	humanized monoclonal antibody	IL-17A neutralizer

Vaccines

Many vaccines are grown in tissue cultures.

Gene therapy

involves artificially manipulating a virus to include a desirable piece of genetic material.
Viral gene therapies using engineered plant viruses have been proposed to enhance crop performance and promote sustainable production.

Biosimilars

With the expiration of many patents for blockbuster biologics between 2012 and 2019, the interest in biosimilar production, i.e., follow-on biologics, has increased. Compared to small molecules that consist of chemically identical active ingredients, biologics are vastly more complex and consist of a multitude of subspecies. Due to their heterogeneity and the high process sensitivity, originators and follow-on biosimilars will exhibit variability in specific variants over time. The safety and clinical performance of both originator and biosimilar biopharmaceuticals must remain equivalent throughout their lifecycle. Process variations are monitored by modern analytical tools and describe a unique design space for each biologic.
Biosimilars require a different regulatory framework compared to small-molecule generics. Legislation in the 21st century has addressed this by recognizing an intermediate ground of testing for biosimilars. The filing pathway requires more testing than for small-molecule generics, but less testing than for registering completely new therapeutics.
In 2003, the European Medicines Agency introduced an adapted pathway for biosimilars, termed similar biological medicinal products. This pathway is based on a thorough demonstration of comparability of the product to an existing approved product. Within the United States, the Patient Protection and Affordable Care Act of 2010 created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product. Researchers are optimistic that the introduction of biosimilars will reduce medical expenses to patients and the healthcare system.