A medical device is any device intended to be used for medical purposes. Thus what differentiates. Medical devices benefit patients by helping health care providers diagnose and treat patients and helping patients overcome sickness or disease, improving their quality of life. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assurance before regulating governments allow marketing of the device in their country; as a general rule, as the associated risk of the device increases the amount of testing required to establish safety and efficacy increases. Further, as associated risk increases the potential benefit to the patient must increase. Discovery of what would be considered a medical device by modern standards dates as far back as c. 7000 BC in Baluchistan where Neolithic dentists used flint-tipped drills and bowstrings. Study of archeology and Roman medical literature indicate that many types of medical devices were in widespread use during the time of ancient Rome.
In the United States it wasn't until the Federal Food and Cosmetic Act in 1938 that medical devices were regulated. In 1976, the Medical Device Amendments to the FD&C Act established medical device regulation and oversight as we know it today in the United States. Medical device regulation in Europe as we know it today came into effect in the 1993 by what is collectively known as the Medical Device Directive. On May 26th, 2017 the Medical Device Regulation replaced the MDD. Medical devices vary in both indications for use. Examples range from simple, low-risk devices such as tongue depressors, medical thermometers, disposable gloves, bedpans to complex, high-risk devices that are implanted and sustain life. One example of high-risk devices are those with Embedded software such as pacemakers, which assist in the conduct of medical testing and prostheses. Items as intricate as housings for cochlear implants are manufactured through the deep drawn and shallow drawn manufacturing processes; the design of medical devices constitutes a major segment of the field of biomedical engineering.
The global medical device market reached $209 billion USD in 2006 and was estimated to be between $220 and $250 billion USD in 2013. The United States controls ~40% of the global market followed by Europe and the rest of the world. Although collectively Europe has a larger share, Japan has the second largest country market share; the largest market shares in Europe belong to Germany, Italy and the United Kingdom. The rest of the world comprises regions like Australia, China and Iran; this article discusses what constitutes a medical device in these different regions and throughout the article these regions will be discussed in order of their global market share. A global definition for medical device is difficult to establish because there are numerous regulatory bodies worldwide overseeing the marketing of medical devices. Although these bodies collaborate and discuss the definition in general, there are subtle differences in wording that prevent a global harmonization of the definition of a medical device, thus the appropriate definition of a medical device depends on the region.
A portion of the definition of a medical device is intended to differentiate between medical devices and drugs, as the regulatory requirements of the two are different. Definitions often recognize In vitro diagnostics as a subclass of medical devices and establish accessories as medical devices. Section 201 of the Federal Food Drug & Cosmetic Act defines a device as an "instrument, implement, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them Intended for use in the diagnosis of disease or other conditions, or in the cure, treatment, or prevention of disease, in man or other animals, or Intended to affect the structure or any function of the body of man or other animals, andwhich does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and, not dependent upon being metabolized for the achievement of its primary intended purposes.
The term'device' does not include software functions excluded pursuant to section 520." According to Article 1 of Council Directive 93/42/EEC, ‘medical device’ means any "instrument, appliance, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings for the purpose of: diagnosis, monitoring, treatment or alleviation of disease, monitoring, alleviation of or compensation for an injury or handicap, replacement or modification of the anatomy or of a physiological process, control of conception,and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means. The New Approach, defined in a European Council Resolution of May 1985, represents an innovative way of technical harmonisation.
It aims to remo
Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on efficacy, they are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators enroll volunteers or patients into small pilot studies, subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, they can involve a single research center or multiple centers, in one country or in multiple countries.
Clinical study design aims to ensure the scientific reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug; the sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become an approved drug; some clinical trials involve healthy subjects with no pre-existing medical conditions. Other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment; when participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick. During dosing periods, study subjects remain under supervision for one to 40 nights. Pilot experiments are conducted to gain insights for design of the clinical trial to follow.
There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy" or "effectiveness". Neither is an absolute criterion; the benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care, are used for a life-threatening condition. In the US, the elderly constitute 14 % of the population. People over 55 are excluded from trials because their greater health issues and drug use complicate data interpretation, because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are frequently excluded. Pregnant women are excluded due to potential risks to the fetus; the sponsor designs the trial in coordination with a panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type of patients might benefit.
If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment and collect data on the subjects' health for a defined time period. Data include measurements such as vital signs, concentration of the study drug in the blood or tissues, changes to symptoms, whether improvement or worsening of the condition targeted by the study drug occurs; the researchers send the data to the trial sponsor, who analyzes the pooled data using statistical tests. Examples of clinical trial goals include assessing the safety and relative effectiveness of a medication or device: On a specific kind of patient, for example, a patient, diagnosed with Alzheimer's disease At varying dosages, for example, a 10 milligram dose instead of a 5 milligram dose For a new indication Evaluation for improved efficacy in treating a patient's condition as compared to the standard therapy for that condition Evaluation of the study drug or device relative to two or more approved/common interventions for that condition, for example, device A versus device B, or therapy A versus therapy B)While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo.
Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol. The protocol is the trial's "operating manual" and ensures that all researchers perform the trial in the same way on similar subjects and that the data is comparable across all subjects; as a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, psychological therapies, or other interventions. Clinical trials may be required before a national regulatory authority approves marketing of the innovation. To drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket appr
A health professional may operate within all branches of health care, including medicine, dentistry, pharmacy, nursing or allied health professions. A health professional may be a public/community health expert working for the common good of the society. Healthcare practitioners include and a wide variety of other human resources trained to provide some type of health care service, they work in hospitals, healthcare centres and other service delivery points, but in academic training and administration. Some provide care and treatment services for patients in private homes. Many countries have a large number of community health workers who work outside formal healthcare institutions. Managers of healthcare services, health information technicians, other assistive personnel and support workers are considered a vital part of health care teams. Healthcare practitioners are grouped into health professions. Within each field of expertise, practitioners are classified according to skill level and skill specialization.
“Health professionals” are skilled workers, in professions that require extensive knowledge including university-level study leading to the award of a first degree or higher qualification. This category includes physicians, physician assistants, midwives, registered nurses, physiotherapists, operating department practitioners and others. Allied health professionals referred to as "health associate professionals" in the International Standard Classification of Occupations, support implementation of health care and referral plans established by medical and other health professionals, require formal qualifications to practice their profession. In addition, unlicensed assistive personnel assist with providing health care services as permitted. Another way to categorize healthcare practitioners is according to the sub-field in which they practice, such as mental health care and childbirth care, surgical care, rehabilitation care, or public health. A mental health practitioner is a health worker who offers services for the purpose of improving the mental health of individuals or treating mental illness.
These include psychiatrists, clinical psychologists, clinical social workers, psychiatric-mental health nurse practitioners and family therapists, mental health counselors, as well as other health professionals and allied health professions. These health care providers deal with the same illnesses, disorders and issues; the most significant difference across categories of mental health practitioners is education and training. A maternal and newborn health practitioner is a health worker who deals with the care of women and their children before and after pregnancy and childbirth; such health practitioners include obstetricians, obstetrical nurses and many others. One of the main differences between these professions is in the training and authority to provide surgical services and other life-saving interventions. In some developing countries, traditional birth attendants, or traditional midwives, are the primary source of pregnancy and childbirth care for many women and families, although they are not certified or licensed.
A geriatric care practitioner plans and coordinates the care of the elderly and/or disabled to promote their health, improve their quality of life, maintain their independence for as long as possible. They include geriatricians, adult-gerontology nurse practitioners, clinical nurse specialists, geriatric clinical pharmacists, geriatric nurses, geriatric care managers, geriatric aides, Nursing aides and others who focus on the health and psychological care needs of older adults. A surgical practitioner is a healthcare professional who specializes in the planning and delivery of a patient's perioperative care, including during the anaesthetic and recovery stages, they may include general and specialist surgeons, surgeon's assistant, assistant surgeon, surgical assistant, anesthesiologists, anesthesiologist assistant, nurse anesthetists, surgical nurses, clinical officers, operating department practitioners, anaesthetic technicians, perioperative nursing, surgical technologists, others. A rehabilitation care practitioner is a health worker who provides care and treatment which aims to enhance and restore functional ability and quality of life to those with physical impairments or disabilities.
These include physiatrists, rehabilitation nurses, clinical nurse specialists, nurse practitioners, orthotists, occupational therapists, recreational therapists, audiologists and language pathologists, respiratory therapists, rehabilitation counsellors, physical rehabilitation therapists, athletic trainers, physiotherapy technicians, orthotic technicians, prosthetic technicians, personal care assistants, others. Care and treatment for the eye and the adnexa may be delivered by ophthalmologists specializing in surgical/medical care, or optometrists specializing in refractive management and medical/therapeutic care. Medical diagnosis providers are health workers responsible for the process of determining which disease or condition explains a person's symptoms and signs, it is most referred to as diagnosis with the medical context being implicit. This involves a team of healthcare providers in various diagnostic units; these include radiographers, medical laboratory scientists and related professionals.
A dental care practitioner is a health worker who provides care and treatment to promote and restore oral health. These include dentists and dental surgeons, dental assistants
The BMJ is a weekly peer-reviewed medical journal. It is one of the world's oldest general medical journals. Called the British Medical Journal, the title was shortened to BMJ in 1988, changed to The BMJ in 2014; the journal is published by the global knowledge provider BMJ, a wholly owned subsidiary of the British Medical Association. The editor in chief of The BMJ is Fiona Godlee, appointed in February 2005; the journal began publishing on 3 October 1840 as the Provincial Medical and Surgical Journal and attracted the attention of physicians around the world through its publication of high-impact original research articles and unique case reports. The BMJ's first editors were P. Hennis Green, lecturer on the diseases of children at the Hunterian School of Medicine, its founder and Robert Streeten of Worcester, a member of the PMSA council; the first issue of the British Medical Journal was 16 pages long and contained three simple woodcut illustrations. The longest items were the editors' introductory editorial and a report of the Provincial Medical and Surgical Association's Eastern Branch.
Other pages included a condensed version of Henry Warburton's medical reform bill, book reviews, clinical papers, case notes. There were 2 1⁄2 columns of advertisements. Inclusive of stamp duty it cost 7d, a price which remained until 1844. In their main article and Streeten noted that they had "received as many advertisements for our first number, as the most popular Medical Journal, after seventeen years of existence."In their introductory editorial and statements and Streeten defined "the main objects of promotion of which the Provincial Medical and Surgical Journal is established". Summarised, there were two clear main objectives: the advancement of the profession in the provinces and the dissemination of medical knowledge. Green and Streeten expressed interest in promoting public well-being as well as maintaining'medical practitioners, as a class in that rank of society which, by their intellectual acquirements, by their general moral character, by the importance of the duties entrusted to them, they are justly entitled to hold'.
The BMJ published the first centrally randomised controlled trial. The journal carried the seminal papers on the causal effects of smoking on health and lung cancer and other causes of death in relation to smoking. For a long time, the journal's sole competitor was The Lancet based in the UK, but with increasing globalisation, The BMJ has faced tough competition from other medical journals The New England Journal of Medicine and the Journal of the American Medical Association; the BMJ is an advocate of evidence-based medicine. It publishes research as well as clinical reviews, recent medical advances, editorial perspectives, among others. A special "Christmas Edition" is published annually on the Friday before Christmas; this edition is known for research articles which apply a serious academic approach to investigating less serious medical questions. The results are humorous and reported by the mainstream media; the BMJ has an open peer review system. About half the original articles are rejected after review in-house.
Manuscripts chosen for peer review are first reviewed by external experts, who comment on the importance and suitability for publication, before the final decision on a manuscript is made by the editorial committee. The acceptance rate is less than 7% for original research articles; the BMJ is included in the major indexes PubMed, MEDLINE, EBSCO, the Science Citation Index. The journal has long criticised the misuse of the impact factor to award grants and recruit researchers by academic institutions; the five journals that as of 2008 have cited The BMJ most are The BMJ, Cochrane Database of Systematic Reviews, The Lancet, BMC Public Health, BMC Health Services Research. As of 2008, the five journals that have been cited most by articles published in The BMJ are The BMJ, The Lancet, The New England Journal of Medicine, Journal of the American Medical Association and Cochrane Database of Systematic Reviews. In the 2018 Journal Citation Reports, The BMJ's impact factor was 23.295 in 2017, ranking it fourth among general medical journals.
According to the Web of Science, the following articles have been cited the most often: Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. "Establishing a standard definition for child overweight and obesity worldwide: international survey". BMJ. 320: 1240–3. Doi:10.1136/bmj.320.7244.1240. PMC 27365. PMID 10797032. "Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, stroke in high risk patients". BMJ. 324: 71–86. January 2002. Doi:10.1136/bmj.324.7329.71. PMC 64503. PMID 11786451. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes: prospective observational study". BMJ. 321: 405–12. Doi:10.1136/bmj.321.7258.405. PMC 27454. PMID 10938048; as of 2014, the most viewed article on The BMJ website is: Schultz WW, van Andel P, Sabelis I, Mooyaart E. "Magnetic resonance imaging of male and female genitals during coitus and female sexual arousal".
BMJ. 319: 1596–600. Doi:10.1136/bmj.319.7225.1596. PMC 28302. PMID 10600954. In 1974, Dr. Elaine Murphy submitted a brief case report under her husband's name John which suggested a condition known as Cello Scrotum, a fictional condition which affected male ce
Richard Alan John Asher, FRCP was an eminent British endocrinologist and haematologist. As the senior physician responsible for the mental observation ward at the Central Middlesex Hospital he described and named Munchausen syndrome in a 1951 article in The Lancet. Richard Asher was born to his wife Louise, he married Margaret Augusta Eliot at St Pancras' Church, London on 27 July 1943, whereupon his father-in-law gave him a complete set of the Oxford English Dictionary, which doctor and medical ethicist Maurice Pappworth alleged was the source of Asher's "accidental" reputation as a medical etymologist. They had three children: Peter Asher, a member of the pop duo Peter & Gordon and record producer, Jane Asher, a film and TV actress and novelist, Clare Asher, a radio actress; the Asher family home above his private consulting rooms at 57 Wimpole Street was notable when Paul McCartney lived there in 1964–66 during his relationship with Jane Asher. In 1964 Asher gave up his hospital post and all medical activities.
He suffered from depression in life and died by his own hand at the age of 57. Asher was regarded as "one of the foremost medical thinkers of our times", who emphasised the need "to be critical of our own and other people's thinking". Asher was concerned that "many clinical notions are accepted because they are comforting rather than because there is any evidence to support them". Asher was hailed as a pioneer in challenging the value of excessive bed rest following treatment, argued that the Pel-Ebstein fever was an example of a condition that exists only because it has a name. Asher's 1949 paper "Myxoedematous Madness" alerted a generation of physicians to the interaction between the brain and the thyroid gland; as a result and elderly psychiatric patients are now screened for thyroid malfunction. Some of the'madness' cases are now thought to be the early descriptions of Hashimoto's encephalopathy, a rare neuroendocrine syndrome sometimes presenting with psychosis. Asher is remembered today for his "refreshingly provoking" articles which "sparkle with sequins--his own aphorisms, imaginary dialogue, quotations."
He thought that medical writing should provide "useful and practical knowledge instead of allotov-words-2-obscure-4-any-1,2-succidin-understanding-them." Anthologies of his articles were well-received, with the Talking Sense collection being described as "still the best advice on medical writing." Notable articles include: The Dangers of Going to Bed - "one of the most influential medical papers written" The Seven Sins of Medicine Myxoedematous Madness Munchausen’s syndrome Respectable Hypnosis Why Are Medical Journals So Dull? The Talking Sense trilogy: Clinical Sense with a rueful correction in The Dog in the Night-time Making Sense Talking Sense The "Seven Sins of Medicine" is a lecture delivered by Asher and published in The Lancet, describing medical professional behaviour, considered inappropriate; these sins are quoted to students: Obscurity Cruelty Bad manners Over-specialisation Love of the rare Common stupidity Sloth From 1995–2010 an annual prize in memory of Asher was awarded by the Royal Society of Medicine and the Society of Authors for the best first edition textbook aimed at undergraduate students.
The most recent prize was presented to Hugo Farne, Edward Norris-Cervetto and James Warbrick-Smith for their book "Oxford Cases in Medicine and Surgery" at the Royal Society of Medicine, 27 October 2010
William Boyd (pathologist)
William Boyd, MB, ChB, MD, MRCP, FRCPath, was a Scottish-Canadian physician, pathologist and author known for his medical textbooks. William was born in Portsoy, the sixth child of Dugald Cameron Boyd and Eliza Marion Boyd. Educated at the University of Edinburgh, he graduated M. B. Ch. B. in 1908, M. D. in 1911, went on to become trained and accredited as a neurologist and pathologist. Boyd worked as an attending physician and nominal pathologist at the Derby County Asylum in the English Midlands from 1909–1912, at Winwick Hospital from 1912–1913, he was a pathologist at Wolverhampton Royal Infirmary from 1913 to August 1914. During World War I, Boyd served as a general medical officer in the Royal Army Medical Corps in Flanders at the rank of captain. In 1916 he wrote the book, With a Field Ambulance at Ypres, describing his experiences as both a physician and an ordinary combatant in the war zone. After the conflict, Boyd moved to Canada at the urging of friends from medical school who were working there.
He married Enid Christie, the daughter of a Presbyterian minister, in Winnipeg, Manitoba in June 1919. Boyd became a Professor of Pathology in the Manitoba Medical College at the University of Manitoba in Winnipeg and over the next 22 years, he wrote several pathology textbooks that were published and read internationally; these earned him financial security. In 1937, he moved to the University of Toronto in Toronto, Ontario and in 1951 to the University of British Columbia in Vancouver, British Columbia. Boyd continued to be an active lecturer on medical-pathological topics well into this 80s, spoke in many different countries. In 1968, he was made a Companion of the Order of Canada, Canada's highest civilian honor, "for his services as a pathologist and as a founding member of the National Cancer Institute". Boyd died of pneumonia at the age of 93 in Toronto, he was survived by his wife Enid. Pathology for Surgeons Pathology of Internal Disease Textbook of Pathology Introduction to Medical Science Pathology List of pathologists "Dr. Boyd: After 89 years the mental ability is still there".
The Medical Post: 24. June 11, 1974. "William Boyd". Canada's Digital Collections. Retrieved April 18, 2005. With a field ambulance at Ypres: being letters written March 7 – August 15, 1915 at the Internet Archive William Boyd at The Canadian Encyclopedia William Boyd Museum of Pathology at the Vancouver General Hospital
A biopharmaceutical known as a biologic medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from synthesized pharmaceuticals, they include vaccines, blood components, somatic cells, gene therapies, recombinant therapeutic protein, 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 are isolated from living sources—human, 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 to engineered macromolecular products like protein- and nucleic acid-based drugs, distinguishing them from products like blood, blood components, or vaccines, which are extracted directly from a biological source.
Specialty drugs, a recent classification of pharmaceuticals, are high-cost drugs that are 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, combinations thereof. Within EMA contexts, the term advanced therapies refers to ATMPs, although that term is rather nonspecific outside those contexts. Gene-based and cellular biologics, for example are at the forefront of biomedical research, 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. Some of the oldest forms of biologics are extracted from the bodies of animals, other humans especially.
Important biologics include: Whole blood and other blood components Organs and tissue transplants Stem cell therapy Antibodies for passive immunization Human breast milk Fecal microbiota Human reproductive cellsSome biologics that were extracted from animals, such as insulin, are now more produced by recombinant DNA. As 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 that are produced by means of biological processes involving recombinant DNA technology; these medications are one of three types: Substances that are identical to the body's own key signalling 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 to counteract or block any given substance in the body, or to target any specific cell type.
Receptor constructs based on a 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 rheumatology and oncology, but cardiology, gastroenterology and others. In most of these disciplines, biologics have added major therapeutic options for the treatment of many diseases, including some for which no effective therapies were available, others where existing therapies were inadequate. However, the advent of biologic therapeutics has raised complex regulatory issues, significant pharmacoeconomic concerns, because the cost for biologic therapies has been higher than for conventional medications; this factor has been relevant since many biological medications are used for the treatment of 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 common indications is 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, 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 (insulin, growth hormone, gonadotr