A biopharmaceutical, also known as a biologic(al) medical product, biological, Definition of "biological" at Oxford Dictionaries or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living cells used in cell therapy. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living cells or tissues. They (or their precursors or components) are isolated from living sources—human, animal, plant, fungal, or microbial. Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. 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. 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 (ATMPs) 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 biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available. In some jurisdictions, biologics are regulated via different pathways than other small molecule drugs and medical devices. The term biopharmacology is sometimes used to describe the branch of pharmacology that studies biopharmaceuticals.
Major classesis a type of biopharmaceutical directly extracted from living systems.]]
Extracted from living systemsSome 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
- Organs and tissue transplants
- Stem cell therapy
- Antibodies for passive immunization (e.g., to treat a virus infection)
- Human breast milk
- Fecal microbiota
- Human reproductive cells
Produced by recombinant DNAAs indicated the term "biologics" can be used to refer to a wide range of biological products in medicine. However, in most cases, the term "biologics" is used more restrictively for a class of therapeutics (either approved or in development) that are produced by means of biological processes involving recombinant DNA technology. These medications are usually one of three types:
- Substances that are (nearly) identical to the body's own key signalling proteins. Examples are the blood-production stimulating protein erythropoetin, or the growth-stimulating hormone named (simply) " 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" (using hybridoma technology or other methods) 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 ( fusion proteins), 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.
- Blood factors ( Factor VIII and Factor IX)
- Thrombolytic agents ( tissue plasminogen activator)
- Hormones ( insulin, glucagon, growth hormone, gonadotrophins)
- Haematopoietic growth factors ( Erythropoietin, colony stimulating factors)
- Interferons (Interferons-α, -β, -γ)
- Interleukin-based products (Interleukin-2)
- Vaccines ( Hepatitis B surface antigen)
- Monoclonal antibodies (Various)
- Additional products ( tumour necrosis factor, therapeutic enzymes)
VaccinesMany vaccines are grown in tissue cultures.
Gene therapyViral gene therapy involves artificially manipulating a virus to include a desirable piece of genetic material.
BiosimilarsWith the expiration of numerous 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, neither originators nor follow-on manufacturers produce reliably constant quality profiles over time. The process variations are monitored by modern analytical tools (e.g., liquid chromatography, immunoassays, mass spectrometry, etc.) and describe a unique design space for each biologic. Thus, 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 "similar" 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.; A major hope linked to the introduction of biosimilars is a reduction of costs to the patients and the healthcare system.
CommercializationWhen a new biopharmaceutical is developed, the company will typically apply for a patent, which is a grant for exclusive manufacturing rights. This is the primary means by which the developer of the drug can recover the investment cost for development of the biopharmaceutical. The patent laws in the United States and Europe differ somewhat on the requirements for a patent, with the European requirements are perceived as more difficult to satisfy. The total number of patents granted for biopharmaceuticals has risen significantly since the 1970s. In 1978 the total patents granted was 30. This had climbed to 15,600 in 1995, and by 2001 there were 34,527 patent applications. Blood products and other human derived biologics like breast milk, have highly regulated or very hard to access markets, therefore, customers generally face a supply shortage for these products due to their nature and often institutions housing these biologics, designated as 'banks', cannot distribute their product to customers effectively. Conversely, banks for Reproductive cells are much more widespread and available due to the ease of which spermatozoa and egg cells are able to be used for fertility treatment. Donate Sperm|website=www.spermdonorsaustralia.com.au|access-date=2016-09-29}}
Large-scale productionBiopharmaceuticals may be produced from microbial cells (e.g., recombinant E. coli or yeast cultures), mammalian cell lines (see cell culture) and plant cell cultures (see plant tissue culture) and moss plants in bioreactors of various configurations, including photo-bioreactors. Important issues of concern are cost of production (low-volume, high-purity products are desirable) and microbial contamination (by bacteria, viruses, mycoplasma). Alternative platforms of production which are being tested include whole plants ( plant-made pharmaceuticals).
TransgenicsA potentially controversial method of producing biopharmaceuticals involves transgenic organisms, particularly plants and animals that have been genetically modified to produce drugs. This production is a significant risk for the investor, due to production failure or scrutiny from regulatory bodies based on perceived risks and ethical issues. Biopharmaceutical crops also represent a risk of cross-contamination with non-engineered crops, or crops engineered for non-medical purposes. One potential approach to this technology is the creation of a transgenic mammal that can produce the biopharmaceutical in its milk, blood, or urine. Once an animal is produced, typically using the pronuclear microinjection method, it becomes efficacious to use cloning technology to create additional offspring that carry the favorable modified genome. The first such drug manufactured from the milk of a genetically modified goat was ATryn, but marketing permission was blocked by the European Medicines Agency in February 2006. This decision was reversed in June 2006 and approval was given August 2006.
European UnionIn the European Union, a biological medicinal product is one of the active substance(s) produced from or extracted from a biological (living) system, and requires, in addition to physico-chemical testing, biological testing for full characterisation. The characterisation of a biological medicinal product is a combination of testing the active substance and the final medicinal product together with the production process and its control. For example:
- Production process – it can be derived from biotechnology or from other technologies. It may be prepared using more conventional techniques as is the case for blood or plasma-derived products and a number of vaccines.
- Active substance – consisting of entire microorganisms, mammalian cells, nucleic acids, proteinaceous, or polysaccharide components originating from a microbial, animal, human, or plant source.
- Mode of action – therapeutic and immunological medicinal products, gene transfer materials, or cell therapy materials.
United StatesIn the United States, biologics are regulated by the FDA's Center for Biologics Evaluation and Research (CBER) whereas drugs are regulated by the Center for Drug Evaluation and Research. Approval may require several years of clinical trials, including trials with human volunteers. Even after the drug is released, it will still be monitored for performance and safety risks. The manufacture process must satisfy the FDA's "Good Manufacturing Practices", which are typically manufactured in a clean room environment with strict limits on the amount of airborne particles.
- Antibody-drug conjugate
- Genetic engineering
- List of recombinant proteins
- List of pharmaceutical companies