Index IntroductionPerspective and ConclusionReferences:IntroductionAllergan plc is an Irish pharmaceutical company that acquires, develops and markets branded drugs. Allergan produces a number of different breast implant variations under the Natrelle brand that include 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 prostheses. As of July 24, 2019, the FDA had received 573 unique reports of this cancer, of which 481 were associated with Allergan, including 12 deaths that may be a cause attributable to this cancer. Additionally, FDA reports suggest that the risk of BIA-ALCL is six times higher with Allergan textured implants compared to other textured breast implant manufacturers in the United States. As a result, Allergan voluntarily recalled its Biocell textured implants. This will fundamentally help ensure that unused products are removed from suppliers and doctors' sites. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get Original EssayBIA- ALCL is a type of lymphoma and 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 a capsule. In most cases, BIA-ALCL is found within this capsule. According to data available on the FDA website, BIA-ALCL is found in patients with textured implants. The main difference between textured and non-textured implants is that textured implants develop scar tissue that helps the implants stay in their original position compared to smooth implants. The current information available is very limited and yet there is no concrete evidence of the association of BIA-ALCL with textured breast implants. The incidence rate of BIA-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, lumps, swelling, or shape asymmetry. In most cases, these symptoms were experienced years after the implants were placed. This event gained much attention in the media when two women who underwent breast implant surgery filed a lawsuit against Allergan seeking monetary compensation for themselves and other women with implants for removal of the recalled implants, surgical expenses, monitoring and diagnostics. On the other hand, due to the unavailability of substantial evidence of an association between Allergan implants and BIA-ALCL, Allergan announced on July 30 that it will only pay the cost of the new implants and not the cost of the surgery. The US FD&C defines an implant as a "device inserted into a surgically or naturally created human body cavity 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 avoid any post-market recalls, each stage of the development cycle becomes crucial, i.e. product development, non-clinical trials, clinical trials and post-market . surveillance. Almost all devices fall under FDA regulation or are Class II devices: moderate risk device – which comescleared for marketing via 510(k) pre-market notification and GMP submission gateway upon demonstration of “substantial equivalence” or Class III device: higher risk device, which is cleared for marketing through the PMA approval process pre-marketing following reasonable demonstration of safety and efficacy. In order to provide supporting data to obtain marketing authorization, these devices undergo a series of non-clinical tests (tests conducted on animals and/or benchtop), followed by clinical studies (tests conducted on humans) as per guidelines.documents published by national/international regulatory and standards bodies. This data is submitted and reviewed by the FDA to approve marketing authorization. The clinical trial is the most crucial phase in the process of bringing the product to market and obtaining regulatory approval. There are numerous regulations governing clinical trials that ensure that the safety, well-being, and rights of participating subjects are protected, and substantial data on safety and efficacy are ultimately collected. The overall goal of clinical trials is to establish a product that is safe and effective and that the associated benefits outweigh the risks. The process of conducting clinical trials is mainly divided into three phases. Phase I studies are performed to evaluate the safety of the device spanning several months. It is carried out on healthy volunteers (20 to 100) who generally receive compensation for participating in the studies. The study is designed to examine how the drug is absorbed, metabolized and excreted. It also examines the effects associated with increasing dosage levels. While in Phase II the effectiveness of a drug is tested which can last from several months to 2 years. This study involves several hundred patients and these studies are often blinded, meaning some patients are given an "experimental" drug while others are given a "control" drug which represents the standard treatment. This allows investigators to provide pharmaceutical companies and the FDA with comparative information. Phase III studies involve random, blinded testing of several hundred or thousands of people and can last up to several years. The main purpose of these studies is to provide the pharmaceutical company and the FDA with in-depth knowledge of the product's effectiveness. As was demonstrated in Case Study: 6 Bad to the Bone, poorly designed clinical and nonclinical studies will not generate substantial, credible data and could result in extreme legal consequences for the company. Some of the major 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 mentioned/promoted its product as substantially equivalent (effective and safe) for use by surgeons without even obtaining approval from the FDA, 21 CFR 812.150 : Reports: In some cases, Synthes didn't even bother to report a certain number of deaths in clinical trials. After completion of clinical trials, the company can apply for FDA approval to market the drug. Clinical trials must be conducted in accordance with Good Clinical Practices (GCP). GCP is an international ethical and scientific quality standard that provides guidelines for designing, conducting and reporting clinical trials involving human subjects. The harmonized document for GCP is developed by ICH E6, its main objective is to ensure the rights, safety and well-being of subjects involved in the studies andensure that the data collected during the study is credible. As was found in Case Study: 8 (To be Human), Black men were recruited to participate in the study in exchange for meager benefits that included compensation and the cost of funeral coverage. This was totally 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 (Protection of Human Subjects was developed). The principles of GCP have been incorporated into a number of regulations in the US and EU, such as Directive 2001/20/EC, 2005/28/EC in the EU. While in the United States, regulations similar to those in the EU are being developed. However, there is some unique aspect of US regulations. The first aspect is the Investigational New Drug (IND) Application through which the pharmaceutical company obtains approval to start clinical trials. Broad categories of INDs include preclinical testing, manufacturing information, investigator information, and clinical trial protocols. The Institutional Review Board (IRB) protects the rights and well-being of the human subjects involved in the study, the IRB is appointed by the sponsor which is almost equivalent to the Independent Ethics Committees (IECs) in the EU. After the rigorous process of successfully completing non-clinical and clinical trials, the final step is to present and submit all data in an understandable manner to the FDA to obtain marketing authorization for the product. The FDA puts this data through 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 noted during Case Study 11: The Data Don't Lie, completion of Phase III studies and submission of clinical and nonclinical study data to the FDA does not guarantee FDA approval. The approval process also depends on a number of external factors. For example, a drug-coated balloon (DCB) was likely responsible for numerous deaths, and BD introduced a similar device following the same path. Because the previous similar device was under investigation and no substantial evidence had yet been found that it caused death, the FDA asked BD to submit additional supporting data for their below-the-knee PAD device. Despite these stringent regulations imposed on products before they reach the market, it is not always possible to guarantee that the product on the market is risk-free. For example, in this case, Allergan textured implants were potentially identified as a cause of BIA-ALCL after certain years of the patient having surgery. Therefore, market surveillance becomes necessary for a manufacturer and the FDA to monitor any adverse safety issues that were not evident prior to marketing and enable them to take appropriate action. The FDA has been monitoring this issue since the 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 has been conveyed to healthcare providers and patients . The FDA has since been working to spread awareness and encourage reporting of all cases related to BIA-ALCL. While the FDA does not recommend removing implants without symptoms of BIA-ALCL due to potential risks, it has provided helpful information for patients and doctors to discuss next steps. Additionally, it is not yet clear whether the problem of BIA-ALCL is associated with certain textured breast implant models or with all textured breast implants. In the guidelines published by the FDA it is clearly underlined that the risk of. 2008.