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{{short description|Drug made from biological source}}
{{Redirect|Biologics|the journal|Biologics (journal)}}

A '''biopharmaceutical''', also known as a '''biological medical product''',<ref>{{cite web | url = https://www.lexico.com/en/definition/biological | archive-url = https://web.archive.org/web/20191019144710/https://www.lexico.com/en/definition/biological | url-status = dead | archive-date = October 19, 2019 | title = Biological | work = Oxford Dictionaries }}</ref> or '''biologic''', is any [[pharmaceutical drug]] product manufactured in, extracted from, or [[semisynthesis|semisynthesized]] from [[biology|biological]] sources. Different from [[total synthesis|totally synthesized]] pharmaceuticals, they include [[vaccine]]s, [[whole blood]], blood components, [[allergenic]]s, [[somatic cell]]s, [[gene therapy|gene therapies]], [[tissue (biology)|tissues]], [[recombinant proteins|recombinant therapeutic protein]], and [[living medicine]]s used in [[cell therapy]]. Biologics can be composed of [[sugar]]s, [[protein]]s, [[nucleic acid]]s, or complex combinations of these substances, or may be living cells or tissues. They (or their [[precursor (chemistry)|precursors]] or components) are isolated from [[life|living]] sources—human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine.<ref>{{Cite journal|last=Walsh|first=Gary|date=2018|title=Biopharmaceutical benchmarks 2018|journal=Nature Biotechnology|language=en|volume=36|issue=12|pages=1136–1145|doi=10.1038/nbt.4305|pmid=30520869|issn=1087-0156|doi-access=free}}</ref><ref>{{Cite journal|last1=Ryan|first1=Michael P.|last2=Walsh|first2=Gary|date=2012|title=Veterinary-based biopharmaceuticals|url=https://linkinghub.elsevier.com/retrieve/pii/S0167779912001357|journal=Trends in Biotechnology|language=en|volume=30|issue=12|pages=615–620|doi=10.1016/j.tibtech.2012.08.005|pmid=22995556}}</ref>

Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. Some [[regulatory agency|regulatory agencies]] use the terms ''biological medicinal products'' or '''therapeutic biological product''' to refer specifically to engineered [[macromolecule|macromolecular]] products like protein- and [[nucleic acid]]-based [[drug]]s, distinguishing them from products like blood, blood components, or vaccines, which are usually extracted directly from a biological source.<ref name="pmid18612293">{{cite journal | vauthors = Rader RA | title = (Re)defining biopharmaceutical | journal = Nature Biotechnology | volume = 26 | issue = 7 | pages = 743–51 | date = July 2008 | pmid = 18612293 | doi = 10.1038/nbt0708-743 | doi-access = free }}</ref><ref>{{cite web |url=https://www.fda.gov/AboutFDA/Transparency/Basics/ucm194516.htm|title=Drugs@FDA Glossary of Terms|date=2 Feb 2012|publisher=[[Food and Drug Administration]]|access-date=8 April 2014}}</ref><ref>{{cite book | last = Walsh| first = Gary| name-list-style = vanc | year = 2003 | title = Biopharmaceuticals: Biochemistry and Biotechnology, Second Edition| publisher = John Wiley & Sons Ltd| isbn = 978-0-470-84326-0}}</ref> '''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.<ref name="ncbi_2013">{{cite journal | vauthors = Gleason PP, Alexander GC, Starner CI, Ritter ST, Van Houten HK, Gunderson BW, Shah ND | title = Health plan utilization and costs of specialty drugs within 4 chronic conditions | journal = Journal of Managed Care Pharmacy | volume = 19 | issue = 7 | pages = 542–8 | date = September 2013 | pmid = 23964615 | doi = 10.18553/jmcp.2013.19.7.542 | url = https://www.jmcp.org/doi/pdf/10.18553/jmcp.2013.19.7.542 }}</ref><ref name="nytimes.com_2015_07_16">{{cite web | url=https://www.nytimes.com/2015/07/16/business/specialty-pharmacies-proliferate-along-with-questions.html | title=Specialty Pharmacies Proliferate, Along With Questions | work=New York Times | date=15 July 2015 | access-date=5 October 2015 | author1=Thomas, Kate | author2=Pollack, Andrew |location=Sinking Spring, Pa.}}</ref><ref name="UofW">{{cite web | url=https://courses.washington.edu/pharm542/Week4/slidesSpecialty%20Pharmacy%20%20Managed%20Care%20Strategies%200410.pdf | title=Specialty Pharmacy Managed Care Strategies | access-date=24 September 2015 | last = Murphy | first = Chad O. | name-list-style = vanc }}</ref> 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",<ref name="EMA_CAT">{{Citation |author=European Medicines Agency |author-link=European Medicines Agency |title=Committee for Advanced Therapies (CAT) |url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000266.jsp |access-date=2017-05-15 |section=tooltip definition of advanced therapy medicinal products |postscript=.}}</ref> including gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and combinations thereof.<ref name="EMA_ATMPs">{{Citation |author=European Medicines Agency |author-link=European Medicines Agency |title=Advanced therapy medicinal products: Overview |url=https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overview |access-date=2017-05-15 |postscript=.}}</ref> 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 bio[[medical research]], and may be used to treat a variety of medical conditions for which no other treatments are available.<ref name="FDA_FAQ">{{cite web | url = https://www.fda.gov/AboutFDA/Transparency/Basics/ucm194516.htm | title = What is a biological product? | access-date = 2014-02-09 | author = Center for Biologics Evaluation and Research | date = 2010-04-01 | publisher = U.S. Food and Drug Administration }}</ref>

In some jurisdictions, biologics are regulated via different pathways from other small molecule drugs and [[medical device]]s.<ref name="pmid18958946">{{cite journal |author= United States Food and Drug Administration |title= Supplemental applications proposing labeling changes for approved drugs, biologics, and medical devices. Final rule |journal= Federal Register |volume= 73 |issue= 164 |pages= 49603–10 |date= August 2008 |pmid= 18958946 |url= https://www.govinfo.gov/content/pkg/FR-2008-08-22/pdf/E8-19572.pdf}}</ref>

==Major classes==
[[File:FreshFrozenPlasma.JPG|thumb|right|120px|[[Blood plasma]] is a type of biopharmaceutical directly extracted from living systems.]]

===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 transplant]]s
* [[Stem-cell therapy]]
* [[Antibody|Antibodies]] for [[passive immunity]] (e.g., to treat a [[virus]] infection)
* [[Human fertilization|Human reproductive cells]]
* Human [[breast milk]]
* [[Fecal microbiota transplant|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===
{{See also|Biologics for immunosuppression}}
''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 (either approved or in development) that are produced using biological processes involving [[recombinant DNA]] technology. These medications are usually one of three types:
# Substances that are (nearly) 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 antibody|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 protein]]s), 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 (see below), and significant pharmacoeconomic concerns because the cost for biologic therapies has been dramatically higher than for conventional (pharmacological) 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]].<ref>{{cite journal | vauthors = Kerr LD | title = The use of biologic agents in the geriatric population | journal = J Musculoskel Med | volume = 27 | pages = 175–180 | year = 2010 | url = https://www.rheumatologynetwork.com/view/use-biologic-agents-geriatric-population}}</ref>

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 ([[Factor VIII]] and [[Factor IX]])
*Thrombolytic agents ([[tissue plasminogen activator]])
*[[Hormone]]s ([[insulin]], glucagon, growth hormone, gonadotrophins)
*Haematopoietic growth factors ([[Erythropoietin]], [[colony-stimulating factor]]s)
*[[Interferon]]s (Interferons-α, -β, -γ)
*[[Interleukin]]-based products (Interleukin-2)
*[[Vaccine]]s ([[Hepatitis B]] surface [[antigen]])
*[[Monoclonal antibody|Monoclonal antibodies]] (Various)
*Additional products ([[tumour necrosis factor]], therapeutic enzymes)

Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2 billion in 2008.<ref>{{cite web
| author=BriskFox Financial
| title=Biopharmaceutical sector sees rising R&D despite credit crunch, finds analysis
| url=http://www.briskfox.com/open/years/2009_q1/do_v_c44751.php
| access-date=2009-03-11 }}</ref> A few examples of biologics made with [[recombinant DNA]] technology include:

{| class="wikitable"
! [[United States Adopted Name|USAN]]/[[International Nonproprietary Name|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]]
| [[Tumor necrosis factor-alpha|TNF]] [[receptor antagonist|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 antibody|humanized]] monoclonal antibody
| [[HER2/neu]] (erbB2) antagonist
|-
| [[ustekinumab]]
| Stelara
| [[psoriatic arthritis]], [[psoriasis]], [[ulcerative colitis]], [[Crohn's disease]]
| [[humanized antibody|humanized]] monoclonal antibody
| [[Interleukin 12|IL-12]] and [[Interleukin 23|IL-23]] antagonist
|-
| [[denileukin diftitox]]
| Ontak
| cutaneous T-cell lymphoma (CTCL)
| Interleukin-2|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]]
| [[Tumor necrosis factor-alpha|TNF]] [[receptor antagonist|antagonist]]
|-
|}

===Vaccines===
{{Main article|Vaccine}}
Many vaccines are grown in tissue cultures.

===Gene therapy===
[[Viral gene therapy]] involves artificially manipulating a [[virus]] to include a desirable piece of genetic material.

==Biosimilars==
{{Main article|Biosimilar}}
With the expiration of many [[patents]] for [[Blockbuster drug|blockbuster biologics]] between 2012 and 2019, the interest in biosimilar production, i.e., follow-on biologics, has increased.<ref name=biosimilars>{{cite journal | vauthors = Calo-Fernández B, Martínez-Hurtado JL | title = Biosimilars: company strategies to capture value from the biologics market | journal = Pharmaceuticals | volume = 5 | issue = 12 | pages = 1393–408 | date = December 2012 | pmid = 24281342 | pmc = 3816668 | doi = 10.3390/ph5121393 | doi-access = free }}</ref> 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.<ref name="pmid21478841">{{cite journal | vauthors = Schiestl M, Stangler T, Torella C, Cepeljnik T, Toll H, Grau R | title = Acceptable changes in quality attributes of glycosylated biopharmaceuticals | journal = Nature Biotechnology | volume = 29 | issue = 4 | pages = 310–2 | date = April 2011 | pmid = 21478841 | doi = 10.1038/nbt.1839 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lamanna WC, Holzmann J, Cohen HP, Guo X, Schweigler M, Stangler T, Seidl A, Schiestl M | title = Maintaining consistent quality and clinical performance of biopharmaceuticals | journal = Expert Opinion on Biological Therapy | volume = 18 | issue = 4 | pages = 369–379 | date = April 2018 | pmid = 29285958 | doi = 10.1080/14712598.2018.1421169 | doi-access = free }}</ref> Process variations are monitored by modern analytical tools (e.g., [[liquid chromatography]], [[immunoassay]]s, [[mass spectrometry]], etc.) 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.<ref name="biosimilars2012">{{cite journal |vauthors= Nick C |title= The US Biosimilars Act: Challenges Facing Regulatory Approval |url= https://www.researchgate.net/publication/297828539 |journal= Pharm Med |volume= 26 |issue= 3 |pages= 145–152 |year= 2012 |doi= 10.1007/bf03262388 |s2cid= 14604362 |access-date= 2012-06-13}}</ref>

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.<ref name="EMA1">{{cite web |url= http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/12/WC500020062.pdf |title= Questions and answers on biosimilar medicines (similar biological medicinal products) |access-date= 2014-10-11 |author= EMA |date= 2008-10-30 |publisher= European Medicines Agency}}</ref> 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.<ref name=" biosimilars2012"/><ref name="urlwww.gpo.gov">{{Federal Register|75|61497}}; {{cite web |url= https://www.govinfo.gov/content/pkg/FR-2010-10-05/pdf/2010-24853.pdf |title= Approval Pathway for Biosimilar and Interchangeable Biological Products |author= United States Food and Drug Administration |work= Public Hearing; Request for Comments |date= 2010-10-05}}</ref> Researchers are optimistic that the introduction of biosimilars will reduce medical expenses to patients and the healthcare system.<ref name=biosimilars />

==Commercialization==
When a new biopharmaceutical is developed, the company will typically apply for a [[patent]], which is a grant to exclusive manufacturing rights. This is the primary means by which the drug developer can recover the investment cost for development of the biopharmaceutical. The [[United States patent law|patent laws]] in the [[United States]] and [[Europe]] differ somewhat on the requirements for a patent, with the European requirements 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.<ref name="scientific_thomson_2006">{{cite web | first=Luke |last=Foster| title=Patenting in the Biopharmaceutical Industry—comparing the US with Europe| url=http://scientific.thomson.com/free/ipmatters/pii/8180019/| access-date=2006-06-23 |archive-url = https://web.archive.org/web/20060316164416/http://scientific.thomson.com/free/ipmatters/pii/8180019/  |archive-date = 2006-03-16}}</ref> In 2012 the US had the highest IP (Intellectual Property) generation within the biopharmaceutical industry, generating 37 percent of the total number of granted patents worldwide; however, there is still a large margin for growth and innovation within the industry. Revisions to the current IP system to ensure greater reliability for R&D (research and development) investments is a prominent topic of debate in the US as well.<ref>{{cite web|title=Growth and Policies Behind Biopharmaceutical Innovation|url=https://www.phrma.org/press-release/new-report-reveals-growth-trajectories-and-top-policy-factors-affecting-biopharmaceutical-innovation-and-growth|website=phrma.org|publisher=PhRMA|access-date=11 April 2018}}</ref> Blood products and other human-derived biologics such as breast milk have highly regulated or very hard-to-access markets; therefore, customers generally face a supply shortage for these products. Institutions housing these biologics, designated as 'banks', often cannot distribute their product to customers effectively.<ref>{{Cite web|url=https://www.forbes.com/sites/erincarlyle/2012/06/27/blood-money-the-guys-who-trade-your-blood-for-profit/#2ec937e46884|title=The Guys Who Trade Your Blood For Profit|last=Carlyle|first=Erin|website=[[Forbes]]|access-date=2016-09-29}}</ref> Conversely, banks for reproductive cells are much more widespread and available due to the ease with which [[spermatozoon|spermatozoa]] and [[egg cell]]s can be used for fertility treatment.<ref>{{cite web |url=https://www.spermdonorsaustralia.com.au/ |title=Sperm Donors Australia {{!}} Donate Sperm |website=spermdonorsaustralia.com.au |access-date=2016-09-29}}</ref>

== Large-scale production ==
Biopharmaceuticals may be produced from microbial cells (e.g., recombinant [[Escherichia coli|''E. coli'']] or yeast cultures), mammalian cell lines (see [[Cell culture]]) and plant cell cultures (see [[Plant tissue culture]]) and [[moss]] plants in [[bioreactor]]s of various configurations, including [[photo-bioreactors]].<ref name="pmid17701058">{{cite journal | vauthors = Decker EL, Reski R | title = Current achievements in the production of complex biopharmaceuticals with moss bioreactors | journal = Bioprocess and Biosystems Engineering | volume = 31 | issue = 1 | pages = 3–9 | date = January 2008 | pmid = 17701058 | doi = 10.1007/s00449-007-0151-y | s2cid = 4673669 }}</ref> Important issues of concern are cost of production (low-volume, high-purity products are desirable) and microbial contamination (by [[bacteria]], [[virus]]es, [[mycoplasma]]). Alternative platforms of production which are being tested include whole plants ([[plant-made pharmaceuticals]]).

=== Transgenics ===
{{main article|Pharming (genetics)}}
A potentially controversial method of producing biopharmaceuticals involves [[transgenic]] organisms, particularly plants and animals that have been [[genetic engineering|genetically modified]] to produce drugs. This production is a significant risk for its 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 [[Microinjection#Pronuclear injection|pronuclear microinjection]] method, it becomes efficacious to use cloning technology to create additional offspring that carry the favorable modified genome.<ref name="pmid11017040">{{cite journal | vauthors = Dove A | title = Milking the genome for profit | journal = Nature Biotechnology | volume = 18 | issue = 10 | pages = 1045–8 | date = October 2000 | pmid = 11017040 | doi = 10.1038/80231 | s2cid = 10154550 }}</ref> 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.<ref>{{cite web |author=Phillip B. C. Jones |title=European Regulators Curdle Plans for Goat Milk Human Antithrombin |url=https://library.wur.nl/WebQuery/file/cogem/cogem_t44fd4747_001.pdf |access-date=2006-06-23}}</ref> This decision was reversed in June 2006 and approval was given August 2006.<ref>{{cite web |url=http://news.bbc.co.uk/2/hi/science/nature/5041298.stm |title=Go-ahead for 'pharmed' goat drug |access-date=2006-10-25 |work=BBC News |date=2006-06-02}}</ref>

==Regulation==

===European Union===

In the [[European Union]], a biological medicinal product<ref name="urlec.europa.eu">{{cite web |url= https://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/dir_2003_63/dir_2003_63_en.pdf |title= Commission Directive 2003/63/EC amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use |author= The Commission of the European Communities |work= Official Journal of the European Union |date= 2003-06-25 |page= L 159/62}}</ref> is one of the active substance(s) produced from or extracted from a biological (living) system, and requires, in addition to physicochemical 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 [[Blood plasma|plasma]]-derived products and a number of vaccines.
* Active substance – consisting of entire [[microorganism]]s, 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, [[horizontal gene transfer|gene transfer]] materials, or [[cell therapy]] materials.

===United States===
In the [[United States]], biologics are licensed through the biologics license application (BLA), then submitted to and 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 trial]]s, 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 [[cleanroom]] environment with strict limits on the amount of airborne particles and other microbial contaminants that may alter the efficacy of the drug.<ref>{{cite book|last1=Kingham|first1=Richard|last2=Klasa|first2=Gabriela|last3=Carver|first3=Krista | name-list-style = vanc |title=Key Regulatory Guidelines for the Development of Biologics in the United States and Europe|date=2014|publisher=John Wiley & Sons, Inc.|pages=75–88|url=https://www.cov.com/-/media/files/corporate/publications/2013/10/chapter4_key_regulatory_guidlines_for_the_development_of_biologics_in_the_united_states_and_europe.pdf|access-date=11 April 2018}}</ref>

===Canada===
In [[Canada]], biologics (and radiopharmaceuticals) are reviewed through the Biologics and Genetic Therapies Directorate within [[Health Canada]].<ref>{{Cite web|url=https://www.canada.ca/en/health-canada/corporate/about-health-canada/branches-agencies/health-products-food-branch/biologics-genetic-therapies-directorate.html|title=Biologics and Genetic Therapies Directorate|access-date=2019-01-20}}</ref>

== See also ==
{{div col|colwidth=20em}}
* [[Antibody-drug conjugate]]
* [[Genetic engineering]]
* [[Host cell protein]]
* [[List of pharmaceutical companies]]
* [[List of recombinant proteins]]
* [[Nanomedicine]]
{{div col end}}

== References ==
{{Reflist|33em}}

== External links ==
* {{MeSH name|Biological Products}}
* {{cite web | url = http://bio.org/speeches/pubs/er/BiotechGuide.pdf | title = Guide to Biotechnology | access-date = 2007-12-17 | author = Debbie Strickland | year = 2007 | publisher = Biotechnology Industry Organization (BIO) | archive-url = https://web.archive.org/web/20070927222631/http://bio.org/speeches/pubs/er/BiotechGuide.pdf | archive-date = 2007-09-27 | url-status = dead }}
* {{cite web | url = http://www.cptech.org/ip/health/biotech/genbio062001.pdf | title = Report for USA Specialty Pharmaceuticals: Generic Biologics: The Next Frontier | access-date = 2007-12-17 |author1=Timothy B. Coan |author2=Ron Ellis | date = 2001-06-01 | publisher = Consumer Project on Technology }}
* {{cite web | url = http://www.psoriasis.org/treatment/psoriasis/biologics/about.php | title = About biologics | access-date = 2007-12-17 | date = 2006-11-01 | publisher = National Psoriasis Foundation | archive-url = https://web.archive.org/web/20060101134831/http://www.psoriasis.org/treatment/psoriasis/biologics/about.php | archive-date = 2006-01-01 | url-status = dead }}

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Biopharmaceutical - Revision history

imported>Fire at 07:31, 3 January 2023