It was once possible to practice “safe” and “modern” anesthesia without any knowledge of the regulatory and voluntary standards governing anesthesia equipment and practice. This has changed, however, and individual practitioners are now subject to federal and state regulations regarding the use of these devices and are strongly influenced by international standards and agreements. The arena of medical device standards and regulations is complex and arcane, and there is much overlap of authority. This chapter reviews the history, present status, interested parties, relevant standards, standards processes, and pending developments that will affect the clinician in the future. The reader should be left with a good understanding of both the processes and the interested parties in the constantly evolving international setting of standards and regulations.
What Is a Standard?
A standard is a document, established by consensus and approved by a recognized body, that provides for common and repeated use, rules, guidelines, or characteristics for activities or their results, aimed at the achievement of the optimum degree of order in a given context. Standards should be based on the consolidated results of science, technology, and experience, and they should be aimed at the promotion of optimum community benefits. In reality, a standard is an agreed restriction for a common good and a shared benefit.
Regulation of Medical Devices
The rules governing medical devices differ throughout the world. Many different models exist, such as the U.S. Food and Drug Administration (FDA), European Union (EU) CE-marking system, and various registrations, listings, licenses, and approvals in other countries. Efforts have been under way since the early 1990s via organizations such as the Global Harmonization Task Force (GHTF) to better achieve uniformity among national medical device regulatory systems around the world. This is being done with two aims in mind: enhancing patient safety and increasing access to safe, effective, and clinically beneficial medical technologies.
Global Harmonization Task Force
A partnership between regulatory authorities and regulated industry, the GHTF consisted of five founding members: the European Union, United States, Canada, Australia, and Japan. The GHTF intended to foster international harmonization in the regulation of medical devices by the development of a regulatory model and supporting documents to underpin globally harmonized regulation of medical technologies. Regulatory and industry representatives from Europe, the Asia-Pacific region, and North America were encouraged to collaborate and actively participate in the development of guidance documents that describe regulatory practices to ensure the safety, effectiveness, and quality of medical devices. This task has been substantially completed, the GHTF has published many final documents on their Web site, and some countries have based their newly developed regulatory processes on these documents. Notwithstanding this success, little progress has been made by the founding members of the GHTF in the harmonization of their regulatory processes to this model. Many other countries, particularly some of the BRIC countries—Brazil, Russia, India, and China—unsuccessfully attempted to join the GHTF.
The FDA proposed, and the five founding members agreed, that the time had come to dissolve the GHTF and create a new, regulator-only forum with global reach that would consult with other interested groups—including industry, health care professionals, and consumers—in the advancement of regulatory harmonization. In October 2011, the regulatory authorities of Australia, Brazil, Canada, China, the European Union, Japan, and the United States and the World Health Organization (WHO) announced the establishment of the International Medical Device Regulators’ Forum (IMDRF) to replace the GHTF. The IMDRF intends to provide guidance on strategies, policies, directions, and activities to accelerate international medical device regulatory harmonization. Unlike the GHTF, various stakeholder groups, such as industry, academia, health care professionals, and consumer and patient groups, are no longer invited to participate in the steering committee or management committee, although they can be invited to participate in ad hoc working groups.
Medical Device Regulation in the United States
Manufacturers of medical devices distributed in the United States must comply with certain basic regulatory requirements:
Quality Systems (QS) regulation
Premarket Notification 510(k), unless exempt, or Premarket Approval (PMA)
Medical device listing
Medical Device Reporting (MDR)
Definition of Terms
A manufacturer must file its name and all places of business with the FDA. Any additional place of business must be registered immediately. Registration is performed electronically.
Quality System Regulation
The QS regulation requires the manufacturer to have a written quality system that is subject to periodic audit by the FDA. The QS regulation requires every medical device to be designed, manufactured, packed, stored, and installed in conformity with current Good Manufacturing Practices (GMP). The QS regulation requires use of design validation, investigation of complaints, and a corrective and preventive action plan to identify root causes of product nonconformance with standards and specifications and to implement effective actions to prevent recurrence.
Medical devices must be labeled either on the medical device or on its immediate container. The label must identify the company name, trade name, or trade symbol of the manufacturer as well as the name and place of business of the manufacturer, packager, or distributor and the identity of and quantity of the contents of the package. In addition, the labeling of a medical device must provide adequate directions for use and adequate warnings against unsafe use for a layperson, unless the medical device is a prescription medical device, in which case the labeling may be written for health care professionals. The labeling of a prescription medical device may be made available electronically.
Premarket Notification 510(k)
The 510(k) process is designed to ensure, through a quality review process, that marketed medical devices, subject to general and applicable special controls, provide a reasonable assurance of safety and effectiveness. It is also designed to foster innovation. This is achieved by comparing the (new) device to an existing (predicate) moderate-risk medical device and demonstrating that the new medical device is substantially equivalent to the predicate. The 510(k) process applies to moderate-risk medical devices (typically class II; Table 34-1 ).
|Factor||510(k) Premarket Notification||Premarket Approval|
|Classes of devices||Class I and II devices||Class III devices|
|Number annually||2428 ∗||24 ∗|
|Documentation (length)||Depends on type of submission |
Typically 50 to 250 pages
|Typically thousands of pages|
|Regulatory requirement||Reasonable assurance of safety and effectiveness||Reasonable assurance of safety and effectiveness|
|Evidence||“Substantial equivalence”: comparison to an existing predicate medical device||Scientific review process of safety and effectiveness data|
|Clinical studies provided?||Varies depending on device type, overall about 10% with clinical studies||Required for both safety and effectiveness|
|Review period (goal/typical)||90/120 days † (traditionally 74% of submissions † ) |
Average time for anesthesiology branch: 140 days †
|180/410 days ‡|
|Source of required information||21 CFR 807.87||Section 515(c)(1) of the federal Food, Drug, and Cosmetic Act|
|Outside review?||No||FDA Advisory Panel meeting|
|User fees||$4717 §||$220,050 §|
|Additional changes made via PMA supplements|
The premarket approval (PMA) process is designed to ensure that a specific marketed medical device provides a reasonable assurance of safety and effectiveness through a scientific review process of safety and effectiveness data (clinical trials). The PMA process applies to novel medical devices or new high-risk medical devices (typically class III; see Table 34-1 ).
Medical Device Listings
A manufacturer must file a list identifying each medical device made or processed for commercial distribution in the United States and its labels and labeling. Additionally, the manufacturer must provide a notice of discontinuance once a medical device is no longer made. Listing is performed electronically.
Medical Device Reporting
Manufacturers of moderate- and high-risk medical devices (class II or class III) must report to the FDA when they learn of information that reasonably suggests that a medical device has or may have caused or contributed to the death or serious illness of or serious injury to a patient, or when they learn of an event that might contribute to the death or serious illness of or serious injury to a patient should it reoccur.
Medical Device Regulation in the European Union
In the EU, medical devices are regulated by one of three directives: the Medical Devices Directive (MDD), the Active Implantable Medical Devices Directive (AIMDD), or the In Vitro Diagnostic Directive (IVDD). Directives are an instrument from the European Parliament directing each member state to enact a law that embodies the content of the directive. The directives establish the regulatory scheme based on a risk-based classification system and, for higher risk devices, a certified quality system. The directives establish broad safety and performance criteria called the Essential Requirements (ERs). All medical devices are required to demonstrate compliance with the ERs.
Medical Device Regulation in Japan
The Pharmaceutical Affairs Law (PAL) applies to all medical devices in Japan. PAL is controlled by the Ministry of Health, Labor, and Welfare (MHLW). All medical devices are classified with a Japanese classification rule that was basically an adopted GHTF rule. Based on the classification, a medical device can require notification, certification, or approval (respectively, from lower to higher risk and from lower to higher effort). Additionally, certain measuring devices require a separate metrological (pattern) approval.
Medical Device Regulation in China
The State Food and Drug Administration (SFDA) is the central government agency in charge of drug and medical device administration with functions similar to those of the FDA in the United States. All medical devices must be registered with the SFDA before they are exported to or sold in China. The SFDA process requires in-country testing of medical devices for the Chinese market. Additionally, certain measuring devices require a separate metrological approval.
The General Administration of Quality Supervision, Inspection, and Quarantine (AQSIQ) is tasked with oversight, inspection, and quarantine as well as with establishing the technical standards for imported and exported goods. AQSIQ maintains responsibility for certifying electrical safety for a wide variety of products with the so-called China Compulsory Certificate (CCC). The CCC safety license process requires manufacturers to obtain the CCC mark before exporting or selling products listed in the CCC catalog into the Chinese market. The CCC mark is administered by the Certification and Accreditation Administration (CNCA). The China Quality Certification Centre (CQC) is designated by the CNCA to process CCC mark applications. Electrical medical devices require CCC certification prior to SFDA registration.
Role of Standards In Medical Device Regulation
In almost all jurisdictions, standards are used for the detailed requirements used to regulate medical devices, and regulations are used to set the high-level principles. The exception is China, where the standards are written into the law and become part of the regulation.
The U.S. FDA reviews standards and, when found appropriate, recognizes them as suitable by publishing them in the Federal Register (FR). Manufacturers may then use those standards to simplify regulatory submissions. The EU harmonizes standards that they find acceptable by publishing them in the Official Journal (OJ). A harmonized standard has a special status. Medical devices that comply with the relevant harmonized standards are presumed to demonstrate compliance with the relevant essential requirements, and this presumption cannot be easily challenged.
Early Efforts in the United States
The passage of the Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1938 was hastened by a tragedy the previous year in which nearly a hundred people died after ingesting “Elixir Sulfanilamide.” This act included new provisions to:
Extend control to cosmetics and therapeutic medical devices
Start a new system of drug regulation that requires new drugs to be shown to be safe
Loosen misbranding requirements by eliminating the need to prove intent to defraud
Ensure that safe limits be created for unavoidable poisonous substances
Authorize food standards created for identity, quality, and container filling
Authorize medical device factory inspections
Add the remedy of court injunctions against violative manufacturers
Increasing public concern over the safety and effectiveness of medical devices in the late 1960s and early 1970s led to the formation of a study group within the Department of Health, Education, and Welfare, the predecessor of the present Department of Health and Human Services (DHHS). This study group, chaired by Dr. Theodore Cooper of the National Heart, Lung, and Blood Institute, estimated, as did other studies at the time, that over the previous decade more than 10,000 injuries and hundreds of deaths were linked to medical devices still on the market.
Recommendations from this study group formed the basis of the Medical Device Amendments of 1976. The members of the group felt that performance standards would be more effective than a PMA in ensuring the safety and effectiveness of most new medical devices. Since 1976, the FDA and medical device regulation has evolved. A timeline showing significant events since 1976 is shown in Figure 34-1 .
Food and Drug Administration
The Food and Drug Administration is a scientific, regulatory, public health agency whose mission is to protect and promote public health. One of its purposes is to establish a reasonable assurance of the safety and effectiveness of medical devices marketed in the United States. Regulation of medical devices in the United States by the FDA has been undergoing an evolution since the passage of the Medical Device Amendments in 1976. This evolution (see Fig. 34-1 ) has included the passage of several pieces of legislation and the establishment of important reporting and disclosure tools, such as MedWatch ( www.fda.gov/Safety/MedWatch/ucm170520.htm ) and ClinicalTrials.gov .
The meaning of the terms safety and effectiveness is dependent on the risk profile of the medical device. For low-risk medical devices (class I), general postmarketing controls are considered sufficient to provide reasonable assurances of safety and effectiveness. For moderate-risk devices (class II) for which there is sufficient information, so-called special controls —typically a combination of standards and guidance documents—are considered sufficient to provide reasonable assurances of safety and effectiveness. For high-risk devices (class III) or for those medical devices on which there is not sufficient information, scientific evidence from well-controlled clinical trials is required to provide reasonable assurances of safety and effectiveness.
Medical Device Amendments of 1976
In 1976, the Medical Device Amendments (21 U.S.C. Secs. 513 through 521) supplemented the original Federal FD&C Act, which required a “reasonable assurance of safety and effectiveness” before a medical device can be marketed. Section 201(h) of the FD&C Act defined a medical device as:
An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article including any component, part or accessory which is (1) recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (3) intended to affect the structure of the body in man or other animals and which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animal and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes.
These amendments provided the FDA with the authority to regulate medical devices by establishing a three-tiered system of regulation. Manufacturers were required, at the very least, to register with the FDA any new low-risk device. High-risk devices, on the other hand, required PMA, and moderate-risk devices required PMN and FDA clearance prior to being marketed. In all cases, however, the FDA was required to conduct postmarket surveillance of devices after introduction into clinical use, and manufacturers were required to report significant incidents to the FDA.
After the 1976 amendments, problems with an anesthesia machine that led to the death of four patients exposed problems with the regulatory framework in place at that time. This led to congressional hearings and helped lead to the MDR regulations, issued shortly thereafter, which required all manufacturers and distributors of medical devices to report deaths and serious injuries from medical devices to the FDA. During those hearings, the FDA agreed to work to minimize the dangerous use of medical devices, and real efforts for extending the FDA’s Good Manufacturing Practices to cover the design of medical devices began.
A series of legislative changes have been made by Congress to the FD&C Act. They include:
Safe Medical Devices Act (SMDA) of 1990
Medical Device Amendments of 1992
FDA Modernization Act (FDAMA) of 1997
Medical Device User Fee and Modernization Act (MDUFMA) of 2002
Safe Medical Devices Act
The Safe Medical Devices Act (SMDA) was signed into law on November 28, 1990 (Public Law 101-629). Elements of the new law included user reporting of probable device-related issues, distributor/manufacturer reporting of device incidents, changes to the 510(k) clearance and PMA processes, changes to the classification of devices, and changes to the FDA’s internal performance standards process, recall authority, postmarket surveillance, and greater enforcement powers. One of the most important features of this law is that it imposed mandatory requirements on facilities that use medical devices. The user shared the onus, which previously only had fallen to the manufacturer. Thus the FDA has gained some regulatory access and control in the local hospital. With this new law, the emphasis was supposed to have been moved from premarket review to postmarket surveillance. Consistent with this change in philosophy, the processes by which devices are classified and approved were to have been relaxed. There is little evidence that this has happened. All institutions—from major medical centers to small, freestanding ambulatory surgical centers—are now expected to report any information on the death or injury of a patient that may have been caused by a medical device. Both the FDA and the manufacturer must be notified within a specified period of time and in a prescribed manner. In addition, institutions are required to produce biannual reports summarizing all individual reports filed over the past 180 days.
The SMDA made important changes in the law compared with the 1976 Medical Device Amendments, including certain changes in the requirements for all classes of medical devices. The Medical Device Amendments of 1992 were intended to clarify both the Medical Device Amendments of 1976 and the SMDA.
It is interesting to note that within the medical industry, medical devices are now subject to more stringent regulation than is the pharmaceutical industry. This is the case despite the fact that most of the recent congressional investigations and public scandals have been associated with pharmaceuticals.
The act causes the FDA to consolidate several adverse reaction reporting systems under the name MedWatch. The program is designed to provide a single portal for health professionals for the voluntary reporting of problems associated with medical devices. In this program, the FDA partners with a wide variety of organizations, which are encouraged to play an active role in postmarketing surveillance.
Food and Drug Administration Modernization Act (FDAMA) of 1997
The FDAMA included provisions that require the FDA to accelerate review of devices. In response the FDA completed dozens of guidance documents, most of which added requirements for manufacturers. FDAMA included a mandate that the Center for Devices and Radiological Health (CDRH) create a standards program, which has been very successful. FDAMA included provisions for regulation of advertising of unapproved uses of drugs and devices as well as regulation of health claims for foods.
Medical Device User Fee and Modernization Act (MDUFMA) of 2002
The MDUFMA included provisions that permit the FDA to assess fees from sponsors of medical device applications for evaluation. In return the FDA agrees to improve performance to certain goals. MDUFMA included provisions for device establishment inspections by accredited third parties, and new requirements emerged for reprocessed single-use devices. MDUFMA also included provisions that led to the formation of the Office of Combination Products within the Office of the Commissioner to oversee review of products that fall into multiple jurisdictions within the FDA. An excellent review of the regulatory history of the FDA may be found in Section 2 of the recent Institute of Medicine (IOM) report. In late 2012, the MDUFMA was reauthorized for an additional 5 years. This reauthorization includes numerous incremental improvements to the device approval process.
Organization of the Food and Drug Administration
The FDA is an agency within the DHHS. It consists of the following centers and offices:
Office of the Commissioner
National Center for Toxicological Research
Office of Operations
Center for Veterinary Medicine
Office of Medical Products and Tobacco
Center for Devices and Radiological Health (CDRH)
Center for Biologics Evaluation and Research (CBER)
Center for Drug Evaluation and Research (CDER)
Center for Food Safety and Applied Nutrition
Center for Tobacco Products
Office of Regulatory Affairs
The parts of the FDA of most interest to anesthesiologists include the CDRH (devices), CDER (drugs), and CBER (biologics/vaccines, gene therapies). The discussion will focus on the CDRH and its activities.
Center for Devices and Radiological Health
In 1982, the FDA established the CDRH, which was formed from elements of the old Bureau of Medical Devices and the Bureau of Radiological Health. The CDRH has evolved over the past 30 years and now has seven divisions, or offices, that report to the Director’s Office: 1) Compliance, 2) Management Operations, 3) in Vitro Diagnostic Device Evaluation and Safety; 4) Surveillance and Biometrics, 5) Communication, Education, and Radiation Programs, 6) Science and Engineering Laboratories, and 7) Device Evaluation.
The Office of Device Evaluation (ODE) is responsible for the program areas through which medical devices are evaluated or cleared for clinical trials and marketing. These programs include PMA, product development protocol, humanitarian device exemption, investigational device exemption, and premarket notification programs. The ODE is presently divided into five scientific divisions:
Anesthesiology, General Hospital, Infection Control, and Dental Devices
Reproductive, Gastro-Renal, and Urological Devices
Ophthalmic, Neurological, and ENT Devices
Surgical, Orthopedic, and Restorative Devices
Each division is further subdivided. The Anesthesiology, General Hospital, Infection Control, and Dental Devices division is divided into four branches, each with a separate branch chief.
Medical Devices Advisory Committee
The 1976 amendments also established the Medical Devices Advisory Committee, which currently consists of 18 medical device advisory panels that range from immunology to radiology for the purpose of advising the FDA on issues related to the safety and effectiveness of medical devices. These advisory panels include the Anesthesiology and Respiratory Therapy Devices Panel. Each panel has nine members in addition to an FDA employee, who serves as the executive secretary. Seven of the panelists are voting members, and the consumer and industry representatives are nonvoting members. A panel can request consultants when necessary.
In 2010, the FDA changed the procedures of the medical device advisory panels. The panels are no longer being asked to vote on whether to recommend a medical device’s approval or conditions of approval. Instead, they are being asked to vote on the device’s safety and effectiveness and how the device’s benefits compare with its risks. Typically, each of these attributes is voted separately with questions phrased along the lines of:
Do the data included in the product submission provide substantial evidence of safety for the requested indication?
Do the data included in the product submission provide substantial evidence of effectiveness for the requested indication?
Do the available data indicate that the benefits outweigh the risks of the device when used for the requested indication?
This change permits the panel members to focus on the scientific issues, which are more likely related to their expertise, instead of the regulatory issues with which they might not be familiar.
Classification of Devices
Different parts of the world use different classification approaches as illustrated in Table 34-2 .
|Country||Primary Agency||Classification (Legal Basis/Classes)||Premarket Placing on Market ∗|
|Canada||Health Canada ( www.hc-sc.gc.ca )||Food and Drugs Act (RSC, 1985, c. F-27) |
Invasive vs. noninvasive vs. active devices
Classes I to IV
|Establishment license |
|China||State Food and Drug Administration (former.sfda.gov.cn). The General Administration of Quality Supervision, Inspection, and Quarantine is responsible for electrical safety||Regulations for the Supervision and Administration of Medical Devices (Decree 276 of State Council, 2000) |
Class I: routine administration
Class II: further control
Class III: strict control
Includes devices implanted into the human body, those used for life support or sustenance, and those that pose potential risk to the human body
|Product registration certificate |
Licensing of manufacturers and distributors
|European Union||European Union (ec.europa.eu/)||Active Implantable Medical Device Directive 90/383/EEC |
Medical Device Directive 93/42/EEC
In Vitro Diagnostic Medical Device Directive 98/79/EC
|Compliance label (CE marking) |
Responsible person registration
|Japan||Ministry of Health Labor and Welfare (MHLW) ( www.mhlw.go.jp/english/ )||Pharmaceutical Affairs Law |
Class I: general
Class II: certification
Class II: approval
Class III: approval
Class IV: approval
|PMDA Notification |
|United States||Food and Drug Administration ( www.fda.gov )||Title 21 United States Code |
Class I: general controls
Class II: performance standards/special controls
Classification and finding of substantial equivalence (510[k]) or PMA
Europe’s classification system of medical devices is defined in EU directives on medical devices. These top-down classification rules are based on criteria such as the duration of contact with the patient (less than 60 minutes, not more than 30 days, and more than 30 days), the degree of invasiveness, and the part of the body affected by the use of the device.
In the United States, the FDA was required to classify all medical devices into one of three categories per the 1976 amendments, based on the intended use of the device. Intended use refers to objective intent of the persons legally responsible for the labeling of a medical device. The FDA expects the intended use to address:
The intended medical indication
The intended patient population
The intended part of the body or type of tissue applied to or interacted with
The intended user
The conditions of use
The operating principle
The class I to class III designations are used by the FDA to denote increasing scrutiny and controls. The classification of devices was originally determined by panels of experts, who advised the FDA following the adoption of the 1976 amendments. Of the initial 1750 generic types of devices classified, 40% were class I, 50% were class II, and 10% were class III. Device types were grouped into 16 medical specialties referred to as panels . The panels assigned each device type to one of the three regulatory classes based on their assessment of the “level of control necessary to assure the safety and effectiveness of the device.” The classification is risk based, that is, the risk the device poses to the patient and/or the user is a major factor in the class to which it was assigned. Class I includes devices with the lowest risk, and class III includes those with the greatest risk. The class to which a device is assigned determines, among other things, the type of premarketing submission/application required for FDA clearance to market. If a device is classified as class I or II, and if it is not exempt, a 510(k) notification is required for marketing. All medical devices classified as exempt are not subject to premarket review, but the manufacturer is required to register the device with the FDA. For class III devices, a PMA is required unless the device is a preamendment device (on the market prior to the passage of the Medical Device Amendments in 1976, or substantially equivalent to such a device), in which case a 510(k) is required. The FDA has nearly completed the task of either downgrading all preamendment class III devices into class II or calling for a PMA. Once this task has been completed, there will no longer be any class III preamendment devices on the market via the 510(k) process. In essence, the FDA classification system is bottom-up and based on the state of knowledge and medical devices in the late 1970s with some subsequent modification.
All classes of medical devices are subject to General Controls, which are the baseline requirements of the FD&C Act that apply to all medical devices, class I, II, and III.
Despite the congressional mandate to write performance standards for all class II medical devices, this task overwhelmed the CDRH, which had inadequate resources. In response the FDA gave tacit approval to existing national or international standards for this purpose. In doing so, the FDA was not relieved of the responsibility to formulate mandatory performance standards; however, they had indicated informally that their limited resources would not be used where voluntary standards were in effect. The process by which the FDA was to develop a mandatory performance standard was quite complex and involved an FDA-appointed Standards Advisory Committee. To date, only the apnea monitor standard has been developed by this process. As such, voluntary standards were sought and have become widely used, because they represent an excellent starting point. The use of externally developed voluntary consensus standards was helped by the Pentagon and its allies, who persuaded the Office of Management and Budget to issue Circular A-119 in 1982, urging “federal participation in the development and use of voluntary consensus standards.” Circular A-119 was revised and strengthened in 1993.
At present, it is noted that the “CDRH believes that conformance with recognized consensus standards can support a reasonable assurance of safety and/or effectiveness for many applicable aspects of medical devices.”
The current list of recognized standards maintained on the FDA’s Web site ( www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm ) and the standards program are managed by the CDRH Standards Management Staff (SMS). The SMS had been part of the Office of Science and Engineering Laboratories (OSEL) but was elevated to the Office of the Center Director in 2011. SMS is responsible for facilitating the recognition of national and international medical device consensus standards within the CDRH and FDA. The CDRH standards program was created to address the Congressional mandate contained in the FDA Modernization Act (FDAMA) of 1997. SMS ensures appropriate medical device standards are published in the Federal Register at least twice annually. Manufacturers are permitted to use recognized standards to simplify their premarket applications to the FDA. Although CDRH had been involved in the development of medical device standards for decades, FDAMA formalized the process.
Class I: General Controls
Class I medical devices were subject only to general controls to ensure safety and effectiveness. These controlling regulations 1) required that devices be registered; 2) prohibited adulteration or mislabeling of items; 3) provided for notification of risks, repair, replacement, or refund; 4) restricted the sale and distribution of certain devices; and 5) required GMPs as defined by the FDA.
Class II: Performance Standards and Special Controls
Medical devices in class II had to meet performance standards, because general controls were not considered sufficient to guarantee their safety and effectiveness. These devices had to fulfill all requirements of class I in addition to FDA performance standards.
Class III: Substantial Equivalence
A new class III medical device that was available commercially after the enactment date could attempt to claim substantial equivalence to an existing preamendment class III device and thus “ride on the coattails” of similar, older devices. This was provided for under section 510(k) of the FD&C Act. If a manufacturer chose the 510(k) route, the FDA needed PMN. Should the FDA have decided that substantial equivalence did not apply to the particular device, it had to be classified as a class III device. As such, it required PMA and review by the Anesthesiology and Respiratory Devices Review Panel before it could be marketed. The manufacturer’s only other option was to re-petition for reclassification of their device to class I or class II. The FDA generally ruled that a device was not substantially equivalent if 1) its intended use was different, 2) it raised new questions about safety or effectiveness, or 3) it did not perform as well as devices already on the market.
Classifying a Device in the United States
To find the classification of a device, the classification regulation for the device of interest needs to be found either using the FDA’s on-line classification database (Web site) or using the device panel. Part 868, entitled Anesthesiology Devices , includes subparts for diagnostic, monitoring, therapeutic, and miscellaneous devices. Each classified device within each part has a seven-digit number associated with it, referring to the specific code in Title 21 of the Federal Regulations, where it is defined. An anesthesia machine is listed under 21 CFR §868.5160 as a gas machine for anesthesia or analgesia and is defined as:
(a) Gas machine for anesthesia— (1) Identification. A gas machine for anesthesia is a device used to administer to a patient, continuously or intermittently, a general inhalation anesthetic and to maintain a patient’s ventilation. The device may include a gas flowmeter, vaporizer, ventilator, breathing circuit with bag, and emergency air supply. (2) Classification. Class II (performance standards). (b) Gas machine for analgesia— (1) Identification. A gas machine for analgesia is a device used to administer to a patient an analgesic agent, such as a nitrous oxide–oxygen mixture (maximum concentration of 70 percent nitrous oxide). (2) Classification. Class II (performance standards).
Premarket and Placing-on-Market Processes
The processes and tools used to evaluate a product before permitting its introduction to market vary considerably among countries (see Table 34-2 ). In the United States, the approval process (PMA) and marketing clearance (510[k]) of the FDA (see Table 34-1 ) are most often used to place products on the market in the United States. The EU requires compliance with its directives prior to applying CE-marking and the placement of a product in commerce. For medical devices, a manufacturer must demonstrate that the medical device meets the essential requirements of the Medical Device Directive by creating a technical file with the appropriate evidence and creating a Declaration of Conformity signed by a representative of the company prior to introduction. For manufacturers outside the EU, this material must be accessible to a designated Authorized Representative within the EU. The CE-marking approach is intended to ensure free movement of goods and services within the European common market.
Canada requires obtaining a license with the process similar to that of the 510(k) in the United States, from a paperwork perspective. In Asia a wide variety of listings, registrations, and approvals for medical devices exist that range from a simple addition of the medical device to a list to very involved approval processes that require in-country clinical evaluations.
Pending Regulatory Changes in the United States
What is happening in the United States with respect to changes in to the 510(k) and other processes? Following a 1-year internal assessment in August 2010, CDRH’s 510(k) Working Group published a preliminary report consisting of more than 60 recommendations grouped under six findings aimed at improving the Center’s effectiveness in implementing its various missions. The preliminary report focused on three major areas: the need for 1) a rational, well-defined, and consistently interpreted review standard; 2) well-informed decision making; and 3) continuous quality assurance. The report found:
There is insufficient clarity with respect to the definition of “substantial equivalence.”
CDRH’s current practice allows for the use of some types of predicates that may not be appropriate.
The de novo pathway is important and has not been optimally used across the Center.
It is challenging for reviewers to obtain the information they need to make well-supported clearance decisions.
The CDRH’s knowledge management infrastructure is limited.
Variations in the expertise, experience, and training of reviewers and managers, including third-party reviewers, may contribute to inconsistency or uncertainty in 510(k) decision making.
The report committed the FDA to create a large number of new or revised guidance documents aimed at improving the 510(k) program.
The FDA also commissioned the IOM to evaluate the current 510(k) process to see whether it protects patients and promotes innovation, and if not, to evaluate what legislative, regulatory, or administrative changes are recommended to best achieve the goals of the 510(k) process. The IOM report includes an excellent summary of the history of the reform of the 510(k) process. It was issued in July of 2011 and found that the current 510(k) process:
Does not determine safety or efficacy of a medical device
Lacks the legal basis to screen a medical device for safety and efficacy
Was never intended to do either of the above
The IOM report indicated that “rather than continuing to modify the 35-year-old 510(k) process, the IOM concludes that the FDA’s finite resources would be better invested in developing an integrated premarket and postmarket regulatory framework.” The day the IOM report was published, the FDA immediately rejected its conclusion and announced “the 510(k) process should not be eliminated, but the FDA is open to additional proposals and approaches for continued improvement of our device review program.”
The FDA has continued to follow through on its commitments from the 510(k) preliminary report with the following objectives:
Create new or update existing guidances for clarity
Integrate systems and databases to make information more accessible
Issue regulations to cover previously neglected items and transfer of ownership of a 510(k).