Table of ContentsIntroductionOutlook and ConclusionReferences:IntroductionAllergan plc is an Irish pharmaceutical company that acquires, develops and markets branded medicines. Allergan manufactures a number of different variations of breast implants under its Natrelle brand, including silicone-filled, saline-filled, textured, and smooth implants. On July 24, 2019, the FDA took a bold step and asked Allergan to recall its specific variant of textured breast implants to protect women from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a type of rare cancer associated with these implants. . As of July 24, 2019, the FDA has received 573 unique reports of this cancer, 481 of which are associated with Allergan, including 12 deaths that may have been a cause of this cancer. Additionally, FDA reports suggest that the risk of BIA-ALCL is six times higher with Allergan textured implants than with other textured breast implant manufacturers in the United States. As a result, Allergan voluntarily recalled its Biocell textured implants. This will essentially help ensure that unused products are removed from suppliers as well as physician sites. Say no to plagiarism. Get a tailor-made essay on “Why violent video games should not be banned”?Get the original essayBIA-ALCL is a type of lymphoma, not breast cancer. When an implant is placed inside the body, the body develops a layer of fibrous tissue. around the implant and this layer is called capsule. In most cases, the BIA-ALCL is found inside this capsule. According to data available on the FDA website, BIA-ALCL is present in patients with textured implants. The main difference between textured and non-textured implants is that textured implants develop scar tissue which helps the implants stay in their original place compared to smooth implants. The information currently available is very limited and there is still no solid evidence for the association of BIA-ALCL with textured breast implants. The incidence rate of AIM-ALCL in people with textured implants varies widely, from 1 in 3,817 patients to 30,000 patients. Symptoms of BIA-ALCL include, but are not limited to, pain, bumps, swelling, or asymmetry in shape. In most cases, these symptoms appeared years after implant placement. This event gained media attention when two women who had breast implant surgery filed a lawsuit against Allergan seeking damages for themselves and other women with the implants for removal of the breast implants. recalled implants, surgical, monitoring and diagnostic costs. Furthermore, due to the lack of substantial evidence of an association between Allergan implants and BIA-ALCL, Allergan announced on July 30 that it would cover the cost of the new implants only and not the cost of surgery. The US FD&C defines an implant as a “device placed in a surgically or naturally formed cavity of the human body and intended to remain there for a period of 30 days or more.” » For any device manufacturer, in order to ensure the safety and effectiveness of the device and to avoid any post-market recall, each phase of the development cycle becomes crucial, i.e. product development, testing non-clinical, clinical trials and commercialization. monitoring. Almost all devices fall under FDA regulation, whether it is a Class II device:moderate risk – authorized for marketing through a 510(k) pre-market notification and GMP submission gateway after demonstration of “substantial equivalence” or a Class III device: device higher risk - authorized for marketing through pre-market approval - PMA process after reasonable demonstration of safety and effectiveness. In order to provide the supporting data necessary to obtain marketing authorization, these devices are subjected to a certain number of non-clinical tests (tests carried out on animals and/or on a bench), then to clinical trials (tests conducted on humans) in accordance with guidelines, documents published by regulatory bodies and national/international standards. This data is submitted and reviewed by the FDA to approve marketing authorization. The clinical trial is the most crucial step in the process of launching the product into the market and obtaining regulatory approval. There are extensive regulations governing clinical trials that ensure that the safety, well-being, and rights of participating subjects are protected and that substantial data on safety and effectiveness are collected upon completion. The overall goal of clinical trials is to establish a safe and effective product, whose associated benefits outweigh the risks. The process of conducting clinical trials is mainly divided into three phases. Phase I studies are carried out to assess the safety of the device and extend over several months. It is carried out on healthy volunteers (20 to 100) generally paid to participate in the studies. The study aims to examine how the drug is absorbed, metabolized and excreted. It also examines the effects associated with increased dosage levels. In phase II, the effectiveness of a drug is tested and can last from several months to 2 years. This study involves several hundred patients and these studies are often conducted blinded, meaning that some patients receive an “experimental” drug while others receive a “control” drug that constitutes the standard treatment. This allows investigators to provide pharmaceutical companies and the FDA with comparative information. Phase III studies involve random, blind testing of several hundred or even thousands of people and can last several years. The primary goal of these studies is to provide the pharmaceutical company and the FDA with a thorough understanding of the product's effectiveness. As Case Study: 6 Bad to the Bone showed, poorly designed clinical and non-clinical studies will not generate substantial, credible data and could result in extreme legal consequences for the company. Some of the key regulations violated by Synthes include: 21 CFR 812.5: Investigational Device Labeling. Synthes was directly involved in off-label marketing, 21 CFR 812.7: Synthes explicitly stated/promoted its product as being substantially equivalent (effective and safe) for use by surgeons without even obtaining FDA approval, 21 CFR 812.150: Reports: In some cases, Synthes didn't even bother to report a number of deaths in clinical studies. Once clinical trials are completed, the company can seek FDA approval to market the drug. Clinical trials must be conducted in accordance with Good Clinical Practice (GCP). GCP is an international ethical and scientific quality standard that provides guidelines for designing, conducting and reporting trials involving human subjects. The documentharmonized for GCP is developed by ICH E6, its main objective is to guarantee the rights, safety and well-being of the subjects involved in the trials and to ensure the credibility of the data collected during the study. As was discovered in Case Study: 8 (Human), Black men were recruited to participate in the study in exchange for meager benefits that included some compensation and the cost of funerals. This was completely unethical and no information was provided about the risks associated with the syphilis study. This was an eye-opening event that led to the development of 21 CFR 50 (The Protection of Human Subjects was developed). GCP principles have been incorporated into a number of regulations in the United States as well as the EU, such as Directive 2001/20/EC, 2005/28/EC in the EU. In the United States, regulations similar to those in the EU are being developed. However, the American regulations have a unique aspect. The first aspect is the investigational new drug (IND) application through which the pharmaceutical company obtains authorization to launch clinical trials. The broad categories of INDs include preclinical testing, manufacturing information, investigative information, and clinical trial protocols. The Institutional Review Board (IRB) protects the rights and welfare of human subjects involved in the study. The IRB is appointed by the sponsor, almost equivalent to independent ethics committees (IECs) in the EU. After the rigorous process of passing non-clinical and clinical study reviews, the final step is to present and submit all data in an understandable manner to the FDA for obtaining marketing authorization of the product. The FDA subjects this data to a thorough review process and ensures the quality, safety, and effectiveness of the drug and that there are no undue risks associated with the product. As we saw in Case Study 11: Data Does Not Lie, Completion of Phase III Studies and Submission of Clinical and Non-Clinical Study Data to the FDA Does Not Guarantee Approval of the FDA. The approval process also depends on a number of external factors. For example, a drug-coated balloon (DCB) was likely responsible for a number of deaths and BD submitted a similar device in the same setting. Because the previous similar device was under investigation and substantial evidence of its cause in the deaths had yet to be found, the FDA requested BD to submit more supporting data for its PAD device below the knee. Despite these rigorous regulations imposed on products before they reach the market, it is not always possible to guarantee that the product placed on the market is risk-free. For example, in this case, Allergan textured implants were potentially identified as causing BIA-ALCL after certain years of the patient's surgery. Thus, market vigilance becomes necessary for a manufacturer as well as the FDA to monitor any safety-related issues that were not evident prior to marketing and enable it to take appropriate action. The FDA has been monitoring this issue since the very first case of BIA. - ALCL was reported in 2011 and at the same time, information about the association between this cancer and textured breast implants was communicated to healthcare providers and patients. Since then, the FDA has worked to raise awareness and encourage reporting of all cases related to BIA-ALCL. Although the FDA does not recommend removal of implants without symptoms of BIA-ALCL due to potential risks, it has provided useful information for patients and doctors to discuss. 2008.