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37-477: Blinatumomab , sold under the brand name Blincyto , and known informally as blina, is a biopharmaceutical medication used as a second-line treatment for Philadelphia chromosome -negative relapsed or refractory acute lymphoblastic leukemia . It belongs to a class of constructed monoclonal antibodies , bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets

74-431: A CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor . The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell. CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations. The drug (originally known as MT103)

111-399: A license to operate from the sector regulator. This license will set out the conditions by which the companies or organizations operating within the industry must abide. Regulatory regimes vary by country and industry. In the most light-touch forms of regulation, regulatory agencies are typically charged with overseeing a defined industry. Usually they will have two general tasks: In

148-508: 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. 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

185-472: 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 (e.g., liquid chromatography , immunoassays , mass spectrometry , etc.) and describe

222-467: A part of the executive branch of the government and have statutory authority to perform their functions with oversight from the legislative branch. Their actions are often open to legal review . However, some regulatory bodies are industry-led initiatives rather than statutory agencies, and are called 'voluntary organisations'. They may be not-for-profit organisations or limited companies. They derive their authority from members' commitments to abide by

259-1124: A supply shortage for these products. Institutions housing these biologics, designated as 'banks', often cannot distribute their product to customers effectively. Conversely, banks for reproductive cells are much more widespread and available due to the ease with which spermatozoa and egg cells can be used for fertility treatment. Biopharmaceuticals 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 ). A potentially controversial method of producing biopharmaceuticals involves transgenic organisms, particularly plants and animals that have been genetically modified to produce drugs. This production

296-404: 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,

333-785: 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: 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,

370-619: 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 (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,

407-828: Is a lack of effective competition . Examples of regulatory agencies that enforce standards include the Food and Drug Administration in the United States and the Medicines and Healthcare products Regulatory Agency in the United Kingdom ; and, in the case of economic regulation , the Office of Gas and Electricity Markets and the Telecom Regulatory Authority in India . Regulatory agencies may be

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444-453: 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

481-507: Is approved by the US Food and Drug Administration (FDA) for B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease greater than or equal to 0.1% as well as relapsed or refractory B-cell precursor ALL . Blinatumomab is a bispecific T-cell engager (BiTE). It enables a patient's T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites:

518-613: 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

555-549: The CD19 antigen present on B cells . In December 2014, it was approved by the US Food and Drug Administration under the accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval. Blinatumomab is given via intravenous infusion. Blinatumomab was originally approved to treat Philadelphia chromosome -negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults and children. It

592-463: The Center for Health Policy and Outcomes at Memorial Sloan-Kettering Cancer Center , calculated that according to "value-based pricing," assuming that the value of a year of life is US$ 121,000 with a 15% "toxicity discount," the market price of blinatumomab should be US$ 12,612 a month, compared to the market price of US$ 64,260 a month. A representative of Amgen said, "The price of Blincyto reflects

629-652: 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

666-503: The FDA , thus establishing a deadline of 19 May 2015, for completion of the FDA review process. On 3 December 2014, the drug was approved for use in the United States to treat Philadelphia chromosome -negative relapsed or refractory acute lymphoblastic leukemia under the FDA 's accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at

703-613: The Biologics and Genetic Therapies Directorate within Health Canada . Regulatory agency A regulatory agency ( regulatory body , regulator ) or independent agency ( independent regulatory agency ) is a government authority that is responsible for exercising autonomous dominion over some area of human activity in a licensing and regulating capacity. These are customarily set up to strengthen safety and standards, and/or to protect consumers in markets where there

740-436: 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

777-445: The benefit of the public at large). The existence of independent regulatory agencies is justified by the complexity of certain regulatory and directorial tasks, and the drawbacks of political interference. Some independent regulatory agencies perform investigations or audits , and other may fine the relevant parties and order certain measures. In a number of cases, in order for a company or organization to enter an industry, it must obtain

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814-563: 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. Blood products and other human-derived biologics such as breast milk have highly regulated or very hard-to-access markets; therefore, customers generally face

851-426: 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. In Canada , biologics (and radiopharmaceuticals) are reviewed through

888-787: The event that the regulated company is not in compliance with its license obligations or the law, the regulatory agency may be empowered to: In some instances, it is deemed in the public interest (by the legislative branch of government) for regulatory agencies to be given powers in addition to the above. This more interventionist form of regulation is common in the provision of public utilities , which are subject to economic regulation . In this case, regulatory agencies have powers to: The functions of regulatory agencies in prolong "collaborative governance" provide for generally non-adversarial regulation. Ex post actions taken by regulatory agencies can be more adversarial and involve sanctions, influencing rulemaking , and creating quasi-common law. However,

925-419: 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. Biopharmaceutics

962-447: The introduction of biosimilars will reduce medical expenses to patients and the healthcare system. 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 patent laws in the United States and Europe differ somewhat on

999-435: The production process and its control. For example: 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 trials , including trials with human volunteers. Even after

1036-463: 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. In 2012 the US had the highest IP (Intellectual Property) generation within

1073-417: The significant clinical, economic and humanistic value of the product to patients and the health-care system. The price also reflects the complexity of developing, manufacturing and reliably supplying innovative biologic medicines." Biopharmaceutical Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within

1110-513: The standards applied by the regulator, for instance as the UK's Advertising Standards Authority says "The self-regulation system works because it is powered and driven by a sense of corporate social responsibility amongst the advertising industry." Regulatory agencies deal in the areas of administrative law , regulatory law , secondary legislation , and rulemaking (codifying and enforcing rules and regulations, and imposing supervision or oversight for

1147-474: 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,

Blinatumomab - Misplaced Pages Continue

1184-477: The time of approval. When blinatumomab was approved, Amgen announced that the price for the drug would be US$ 178,000 per year, which made it the most expensive cancer drug on the market. Merck's pembrolizumab was priced at US$ 150,000 per year when it launched (in September 2014). At the time of initial approval, only about 1,000 patients in the US had an indication for blinatumomab. Peter Bach, director of

1221-541: 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

1258-546: 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 . Some of the oldest forms of biologics are extracted from the bodies of animals, and other humans especially. Important biologics include: Some biologics that were previously extracted from animals, such as insulin, are now more commonly produced by recombinant DNA . Biologics can refer to

1295-595: 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: 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: Many vaccines are grown in tissue cultures. Viral gene therapy involves artificially manipulating

1332-428: Was developed by a German-American company Micromet , Inc. in cooperation with Lonza ; In 2012, Micromet was purchased by Amgen , which furthered the drug's clinical trials. In July 2014, the FDA granted breakthrough therapy status to blinatumomab for the treatment of acute lymphoblastic leukemia (ALL). In October 2014, Amgen's Biologics License Application for blinatumomab was granted priority review designation by

1369-491: Was given August 2006. In 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 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

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