 | The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject.(August 2018) (Learn how and when to remove this template message) |
Medical device manufacturing, as the name suggests, refers to the production of medical devices. Due to the large amount of regulations in the industry, the production of medical devices presents significant challenges from both engineering and legal perspectives.
The United States medical device industry is one of the largest markets globally, exceeding $110 billion annually. In 2012 it represented 38% of the global market and currently more than 6500 medical device companies exist nationwide. These companies are primarily small-scale operations with fewer than 50 employees. The most medical device companies are in the states: California, Florida, New York, Pennsylvania, Michigan, Massachusetts, Illinois, Minnesota, and Georgia. Washington, Wisconsin, and Texas also have high employment levels in the medical device industry. [1] The industry is divided into the following branches: Electro-Medical Equipment, Irradiation Apparatuses, Surgical and Medical Instruments, Surgical Appliances and Supplies, and Dental Equipment and Supplies. [1]
 |
Medical devices are defined by the US Food and Drug Administration (FDA) as any object or component used in diagnosis, treatment, prevention, or cure of medical conditions or diseases, or affects body structure or function through means other than chemical or metabolic reaction in humans or animals. [2] This includes all medical tools, excluding drugs, ranging from tongue depressors to Computerized Axial Tomography (CAT) scanners to radiology treatments. Because of the wide variety of equipment classified as medical devices, the FDA has no single standard to which a specific device must be manufactured; instead they have created an encompassing guide that all manufacturers must follow. Manufacturers are required to develop comprehensive procedures within the FDA framework in order to produce a specific device to approved safety standards.
The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products. As of 2017, 3/4th of the FDA budget is paid by people who consume pharmaceutical products, due to the Prescription Drug User Fee Act.
The USFDA allows for two regulatory pathways that allow the marketing of medical devices. The first, and by far the most common is the so-called 510(k) clearance process (named after the Food, Drug, and Cosmetic Act section that describes the process). A new medical device that can be demonstrated to be "substantially equivalent" to a previously legally marketed device can be "cleared" by the FDA for marketing as long as the general and special controls, as described below, are met. The vast majority of new medical devices (99%) enter the marketplace via this process. The 510(k) pathway rarely requires clinical trials. The second regulatory pathway for new medical devices is the Premarket Approval process (PMA), described below, which is similar to the pathway for a new drug approval. Typically, clinical trials are required for this premarket approval pathway. [3]
General controls include provisions that relate to:
Special controls were established for cases in which patient safety and product effectiveness are not fully guaranteed by general controls. Special controls may include special labeling requirements, mandatory performance standards and postmarket surveillance. [5] Special controls are specific to each device and classification guides are available for various branches of medical devices. [6]
Postmarketing surveillance (PMS) is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmacovigilance. Since drugs and medical devices are approved on the basis of clinical trials, which involve relatively small numbers of people who have been selected for this purpose – meaning that they normally do not have other medical conditions which may exist in the general population – postmarketing surveillance can further refine, or confirm or deny, the safety of a drug or device after it is used in the general population by large numbers of people who have a wide variety of medical conditions.
Premarket Approval is a scientific review to ensure the device's safety and effectiveness, in addition to the general controls of Class I. [7] [5]
Under the Food, Drug, and Cosmetic Act, the U.S. Food and Drug Administration recognizes three classes of medical devices, based on the level of control necessary to assure safety and effectiveness. [7] The classification procedures are described in the Code of Federal Regulations, Title 21, part 860 (usually known as 21 CFR 860). [8] Devices are classified into three brackets:
Regulations differ by class based on their complexity or the potential hazards in the event of malfunction. Class I devices are the least likely to cause major bodily harm or death in the event of failure, and are subjected to less stringent regulations than are devices categorized as Class II or Class III. [9]
Class I devices are subject to the least regulatory control. Class I devices are subject to "General Controls" as are Class II and Class III devices. [7] [5] [4]
General controls are the only controls regulating Class I medical devices. They state that Class I devices are not intended to be:
Most Class I devices are exempt from premarket notification and a few are also exempted from most good manufacturing practices regulations. [7] [5] [4]
Examples of Class I devices include hand-held surgical instruments, (elastic) bandages, examination gloves, bed-patient monitoring systems, medical disposable bedding, and some prosthetics such as hearing aids. [5] [11]
Class II devices are those for which general controls alone cannot assure safety and effectiveness, and existing methods are available that provide such assurances. [7] [5] Devices in Class II are held to a higher level of assurance and subject to stricter regulatory requirements than Class I devices, and are designed to perform as indicated without causing injury or harm to patient or user. In addition to complying with general controls, Class II devices are also subject to special controls. [5]
Examples of Class II devices include acupuncture needles, powered wheelchairs, infusion pumps, air purifiers, and surgical drapes. [7] [5] [12]
A few Class II devices are exempt from the premarket notification. [5]
A Class III device is one for which insufficient information exists to assure safety and effectiveness solely through the general or special controls sufficient for Class I or Class II devices. [7] [5] These devices are considered high-risk and are usually those that support or sustain human life, are of substantial importance in preventing impairment of human health, pose a potential, unreasonable risk of injury or illness, or are of great significance in preventative care. [5] . For these reasons, Class III devices require premarket approval.
Prior to marketing a Class III device, the rights-holder(s) or person(s) with authorized access must seek FDA approval. The review process may exceed six months for final determination of safety by an FDA advisory committee. Many Class III devices have established guidelines for Premarket Approval (PMA) and increasingly, must comply with unique device identifier regulations. [13] However, with ongoing technological advances many Class III devices encompass concepts not previously marketed, These devices may not fit the scope of established device categories and do not yet have developed FDA guidelines. [14]
Examples of Class III devices that currently require a premarket notification include implantable pacemaker, pulse generators, HIV diagnostic tests, automated external defibrillators, and endosseous implants. [5]
Nanomanufacturing techniques provide a means of manufacturing cellular-scale medical devices (<100μm). They are particularly useful in the context of medical research, where cellular-scale sensors can be produced that provide high-resolution measurements of cellular-scale phenomena. [15] Common techniques in the area are direct-write nanopatterning techniques such as dip-pen nanolithography, electron-beam photolithography and microcontact printing, directed self-assembly methods, and Functional Nanoparticle Delivery (NFP), where nanofountain probes deliver liquid molecular material that is drawn through nanopattern channels by capillary action. [16]
Additive manufacturing (AM) processes are a dominant mode of production for medical devices that are used inside the body, such as implants, transplants and prostheses, for their ability to replicate organic shapes and enclosed volumes that are difficult to fabricate. [17] The inability of donation systems to meet the demand for organ transplantation in particular has led to the rise of AM in medical device manufacturing. [18]
The largest issue in integrating AM techniques into medical device manufacturing is biocompatibility. These issues arise from the stability of 3D printed polymers in the body and the difficulty of sterilizing regions between printed layers. [19] In addition to the use of primary cleaners and solvents to remove surface impurities, which are commonly isopropyl alcohol, peroxides, and bleach, [20] secondary solvents must be use in succession to remove the cleaning chemicals applied before them, a problem that increases with the porosity of the material used. [19] Common compatibility AM materials include nylon [21] and tissue material from the host patient. [20]
Many medical devices have either been successfully attacked or had potentially deadly vulnerabilities demonstrated, including both in-hospital diagnostic equipment [22] and implanted devices including pacemakers [23] and insulin pumps. [24] On 28 December 2016 the US Food and Drug Administration released its recommendations that are not legally enforceable for how medical device manufacturers should maintain the security of Internet-connected devices. [25] [26]
Biomedical Engineering (BME) or Medical Engineering is the application of engineering principles and design concepts to medicine and biology for healthcare purposes. This field seeks to close the gap between engineering and medicine, combining the design and problem solving skills of engineering with medical biological sciences to advance health care treatment, including diagnosis, monitoring, and therapy. Also included under the scope of a biomedical engineer is the management of current medical equipment within hospitals while adhering to relevant industry standards. This involves equipment recommendations, procurement, routine testing and preventative maintenance, through to decommissioning and disposal. This role is also known as a Biomedical Equipment Technician (BMET) or clinical engineering.
Medical software is any software item or system used within a medical context, such as:
Good manufacturing practices (GMP) are the practices required in order to conform to the guidelines recommended by agencies that control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutical products, dietary supplements, and medical devices. These guidelines provide minimum requirements that a manufacturer must meet to assure that their products are consistently high in quality, from batch to batch, for their intended use. The rules that govern each industry may differ significantly; however, the main purpose of GMP is always to prevent harm from occurring to the end user. Additional tenets include ensuring the end product is free from contamination, that it is consistent in its manufacture, that its manufacture has been well documented, that personnel are well trained, and the product has been checked for quality more than just at the end phase. GMP is typically ensured through the effective use of a quality management system (QMS).
In food safety, the concept of substantial equivalence holds that the safety of a new food, particularly one that has been genetically modified (GM), may be assessed by comparing it with a similar traditional food that has proven safe in normal use over time. It was first formulated as a food safety policy in 1993, by the Organisation for Economic Co-operation and Development (OECD).
The United States Federal Food, Drug, and Cosmetic Act, is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration (FDA) to oversee the safety of food, drugs, medical devices, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from New York. In 1968, the Electronic Product Radiation Control provisions were added to the FD&C. Also in that year the FDA formed the Drug Efficacy Study Implementation (DESI) to incorporate into FD&C regulations the recommendations from a National Academy of Sciences investigation of effectiveness of previously marketed drugs. The act has been amended many times, most recently to add requirements about bioterrorism preparations.
A medical device is any device intended to be used for medical purposes. Thus what differentiates a medical device from an everyday device is its intended use. 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 also increases. Further, as associated risk increases the potential benefit to the patient must also increase.
An investigational device exemption (IDE) allows an investigational device to be used in order to collect safety and effectiveness data required to support a premarket approval (PMA) application or a premarket notification [510(k)] submission to Food and Drug Administration (FDA). Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)'s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.
A drug recall removes a prescription or over-the-counter drug from the market. Drug recalls in the United States are made by the FDA or the creators of the drug when certain criteria are met. When a drug recall is made, the drug is removed from the market and potential legal action can be taken depending on the severity of the drug recall.
Title 21 is the portion of the Code of Federal Regulations that governs food and drugs within the United States for the Food and Drug Administration (FDA), the Drug Enforcement Administration (DEA), and the Office of National Drug Control Policy (ONDCP).
Clinical research is a branch of healthcare science that determines the safety and effectiveness (efficacy) of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease. Clinical research is different from clinical practice. In clinical practice established treatments are used, while in clinical research evidence is collected to establish a treatment.
The Center for Devices and Radiological Health (CDRH) is the branch of the United States Food and Drug Administration (FDA) responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices. The CDRH also oversees the radiation safety performance of non-medical devices which emit certain types of electromagnetic radiation, such as cellular phones and microwave ovens.
Medical foods are foods that are specially formulated and intended for the dietary management of a disease that has distinctive nutritional needs that cannot be met by normal diet alone. In the United States they were defined in the Food and Drug Administration's 1988 Orphan Drug Act Amendments and are subject to the general food and safety labeling requirements of the Federal Food, Drug, and Cosmetic Act. In Europe the European Food Safety Authority established definitions for "foods for special medical purposes" (FSMPs) in 2015.
President of the United States George W. Bush signed the Food and Drug Administration Amendments Act of 2007 (FDAAA) on September 27, 2007. This law reviewed, expanded, and reaffirmed several existing pieces of legislation regulating the FDA. These changes allow the FDA to perform more comprehensive reviews of potential new drugs and devices. It was sponsored by Reps. Joe Barton and Frank Pallone and passed unanimously by the Senate.
The United States Food and Drug Administration Modernization Act of 1997 (FDAMA) amended the Federal Food, Drug, and Cosmetic Act. This act is related to the regulation of food, drugs, devices, and biological products by the FDA. These changes were made in order to recognize the changes in the way the FDA would be operating in the 21st century. The main focus of this is the acknowledgment in the advancement of technological, trade, and public health complexities.
A Humanitarian Device Exemption is an approval process provided by the United States Food and Drug Administration allowing a medical device to be marketed without requiring evidence of effectiveness. The FDA calls a device approved in this manner a "Humanitarian Use Device" (HUD).
This article is about the history of the United States Food and Drug Administration.
The Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA) is a piece of American regulatory legislation signed into law on July 9, 2012. It gives the United States Food and Drug Administration (FDA) the authority to collect user fees from the medical industry to fund reviews of innovator drugs, medical devices, generic drugs and biosimilar biologics. It also creates the breakthrough therapy designation program and extends the priority review voucher program to make eligible rare pediatric diseases. The measure was passed by 96 senators voting for and one voting against.
The Medical Device Regulation Act or Medical Device Amendments of 1976 was introduced by the 94th Congress of the United States. Congressman Paul G. Rogers and Senator Edward M. Kennedy were the chairperson sponsors of the medical device amendments. The Title 21 amendments were signed into law on May 28, 1976 by the 38th President of the United States Gerald R. Ford.
Safe Medical Device Amendments of 1990 or Safe Medical Devices Act sanctioned progressive reporting and tracking rules for medical devices classified by the Medical Device Regulation Act. The Act mandates reporting requirements by medical device manufacturers regarding adverse safety events and product effectiveness of devices classified as substantially equivalent to Class III medical devices. The United States Statute established the Health and Human Services Office of International Relations and a U.S. Food and Drug Administration office for regulatory activities concerning healthcare products which are considered a combinational biological, device, or drug product. The Act of Congress transferred the electronic product radiation control provisions established by the Radiation Control for Health and Safety Act.