FDA_Regulatory_Affairs_Third_Edition_----_(Chapter_5_FDA_Medical_Device_Regulation)

FDA Medical Device Regulation

Introduction

• The medical device industry has seen significant innovation since the 1950s and 1960s, leading to therapeutic, monitoring, and diagnostic benefits.

• By the early 1970s, medical devices were becoming so complex that medical professionals couldn't fully assess them.

• Device developers encountered issues with devices interacting unexpectedly with the body and production deficiencies causing injuries and deaths.

• The 1976 Medical Device Amendments to the Food, Drug, and Cosmetic Act of 1938 were driven by this history.

• By 1978, the FDA reviewed the production and clinical testing of medical devices.

• New devices entering the US market had to undergo FDA review through the 510(k) premarket notification or the premarket approval (PMA) process.

• The 1976 Amendments have been modified and now cover the device development process.

• This chapter introduces medical device classification, premarket submissions, clinical research, and manufacturing regulations.

Differences Between Device and Pharmaceutical Regulations

• Both device and pharmaceutical regulations aim to protect public health but approach this differently.

• Device regulations recognize differences between medical devices and pharmaceuticals and their respective industries.

• Therapeutic medical devices often exert effects locally (e.g., cutting tissue, covering a wound), simplifying preclinical and clinical testing compared to pharmaceuticals.

• Many diagnostic devices don't contact the patient, making pharmaceutical safety testing inappropriate.

• The medical device industry has many small companies with limited regulatory staff, unlike the pharmaceutical industry, which has fewer but larger companies.

• The product life cycle for medical devices can be shorter (e.g., 2-3 years) than for pharmaceuticals.

• Many medical device marketing applications (510(k)s and PMA supplements) are for incremental changes.

• Professionals need to understand both the technology and regulations, as short development timelines and strategic decisions can impact the introduction of lifesaving technology.

• The objective is to provide a step-by-step introduction to regulatory issues associated with medical device development.

Is It a Device? Product Jurisdiction

• To determine applicable regulations, one must determine if the product is a device, drug, or biologic.

• Two factors to consider:

  • The indication for use of the product, as determined by management and clearly stated.

  • The primary mode of action for the product.

• Action is achieved through chemical action and metabolism (a drug) or by a physical action (device).

• An alginate wound dressing containing an antibacterial agent is regulated as a device if its primary purpose is a physical barrier and the antibacterial agent enhances that function.

• If the indication is to deliver the antibacterial agent to treat an existing infection, it might be considered a drug.

• Review the definition of a medical device in the 1976 Medical Device Amendments of the Food, Drug, and Cosmetic Act:

1. Recognized in the official National Formulary, or the USP, 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 or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes.

• Intercenter agreements between CDRH, CDER, and CBER discuss jurisdictional issues.

• The Medical Device User Fee Act of 2002 (MDUFA02) established the Office of Combination Products.

• The FDA Office of Combination Products defined the primary mode of action in an August 25, 2005, federal register notice.

• If a sponsor requires an official product jurisdiction determination, they can file a request for designation with the Office of Combination Products.

Types of Medical Devices

• Medical devices range from large imaging systems to small ophthalmic implants.

• Most in vitro diagnostic products (blood and urine tests) are regulated as medical devices.

• Medical devices can be characterized by function and form:

  Function	Form
  Therapeutic	Durable
  Monitoring	Implantable
  Diagnostic	Disposable

• Examples:

  • Lithotripter (sound waves to break up kidney stones): durable therapeutic device.

  • Pacemaker: implantable therapeutic device.

• Issues like reuse, shelf life, and device tracking impact different types of devices differently.

Medical Device Classification

• Classification determines the type of submission required for commercialization (exempt, 510(k), or PMA).

• Three classes of medical devices:

Class I

• Simplest devices, posing the fewest risks and subject to general controls.

• Most are exempt from premarket notification [510(k)] requirements, and some are also exempt from compliance with the Quality System Regulation (QSR).

• The majority of medical device types are class I devices.

• Examples: toothbrushes, oxygen masks, irrigating syringes.

• Even if exempt from premarket notification, manufacturers must comply with other FDA requirements, like good manufacturing practice in the QSR (21 C.F.R. pt. 820 (2008)).

Class II

• Moderate risk devices.

• Require 510(k) premarket notification clearance before commercialization.

• Demonstrate substantial equivalence to a device already through the 510(k) process or on the market before May 28, 1976 (Medical Device Amendments signing).

• Subject to special controls: Office of Device Evaluation (ODE) guidance documents, FDA-accepted international standards, and the QSR.

• Examples: ultrasound imaging systems, Holter cardiac monitors, pregnancy test kits, central line catheters.

• Nearly 4000 class II devices are cleared annually.

Class III

• Require PMA approval before marketing.

• Not substantially equivalent to any class II device.

• Usually technologically innovative devices.

• A small number of class III preamendments 510(k) devices exist; the FDA is working to downclassify these to class II or require PMAs if downclassification isn't justified.

• 37 PMAs were approved in CY2001.

Determining Device Classification

• If the product is similar to other devices on the US market in terms of indication for use and technological characteristics, classification becomes a search of regulations.

• Title 21 of the Code of Federal Regulations (CFR), Parts 862–892 contains descriptions of medical devices by medical practice area.

• Classifications and exemptions from 510(k) or the QSR, if any, are listed in this section.

• The classification database in the CDRH Website is a useful tool for determining device classification.

• If a description in the CFR is consistent with the new device’s characteristics, the device classification listed should apply.

• Identify precedents by searching the 510(k) or PMA databases for competing devices.

Reclassification

• Once the FDA determines a device is a class III PMA device, it remains class III, regardless of competitors.

• Competitors must follow the PMA process.

• This can change if the FDA approves a reclassification petition, downclassifying the device to class II or I.

• Reexamination can be initiated by the FDA or industry.

• The FDA has examined many device types, their overall risk, and problem frequency to downclassify devices.

• This enables the FDA to focus on higher-risk products.

• Industry groups have also submitted successful reclassification petitions.

• There have been recent efforts to increase regulatory oversight of some class II devices.

• For example, in 2011, surgical mesh used to treat pelvic organ prolapse was subject to a FDA public meeting and discussion of reclassifying it from class II to class III.

Introduction to the Medical Device Approval Process Strategic Choices

• Once the device's classification is known, an appropriate regulatory pathway can be identified.

• A medical device developer is frequently presented with more than one regulatory path to the US market, unlike the pharmaceutical regulatory process.

• For example, software analyzing MRI images is a class II 510(k) product if it only measures anatomical structures' size/volume.

• However, if the software detects abnormalities or provides diagnostic information, it would be considered a class III PMA device.

• A device developer may start with a 510(k) for simpler intended use and then move to the more challenging PMA later.

• Both the industry and the FDA prefer to review medical devices as 510(k)s.

• When speed to market is the prime consideration, one always attempts to follow the 510(k) path.

• Even within the 510(k) pathway, there are branches; If the FDA-recognized standards apply to the new device, the sponsor may choose to submit either an abbreviated 510(k) or a traditional 510(k).

• If the FDA-recognized standards apply to the new device, the sponsor may choose to submit either an abbreviated 510(k) or a traditional 510(k). Review time is the same, but an abbreviated 510(k) contains a list of standards followed and a summary of test results instead of complete testing reports.

• A sponsor may choose an alternate test method, in which case the test protocol would need to be included in a traditional 510(k).

• In some cases, device developers may propose a more complex PMA indication for use or suggest the more complicated class III PMA designation.

• This can make sense when the developer may not have a strong intellectual property position but does have sufficient resources to conduct clinical trials.

• This strategy can result in the erection of a regulatory barrier of entry for other, less well-funded organizations; This strategy is often called creation of a “regulatory patent.”

• Another consideration when deciding on a regulatory path is user fees.

• All the submission types mentioned in this section are discussed in more detail in later sections of this chapter.

Modification of Marketed Devices

• Many changes can be made to 510(k) devices by following the design control provisions of the QSR, rather than submission of a new 510(k).

• Even when a new 510(k) is necessary, in many cases, a sponsor can choose to submit a special 510(k); If the sponsor is modifying its own device, the intended use is not changing and the fundamental scientific technology is not changing. The review period for a special 510(k) is 30 days.

• Changes to PMA products follow a more rigid process; Most changes require advance approval via the PMA supplement process. There are several types of PMA supplements with approval times ranging from 30 days to 180 days.

• The sponsor must also submit PMA annual reports that update ODE on all device changes and any new clinical data.

• Both the premarket and postmarket obligations must be considered when determining the preferred route to market; More information on postmarketing issues can be found in “Postmarketing Issues” section.

• The ease of modifying devices and other postmarket considerations also factor into the strategic regulatory planning process; It is far easier to update a 510(k) device than a PMA device.

Design Controls

• Once the product definition and regulatory strategy have been prepared, class II and III device developers must work to comply with the design control provisions of the QSR (21 CFR 820) as the device development process moves forward.

• The QSR is the medical device equivalent of the pharmaceutical current good manufacturing practices (cGMPs).

• The QSR, unlike cGMPs, also regulates the device development process via its design control provisions (21 CFR 820.30); This section describes the device developer’s obligations under the design control provisions of the QSR. Other sections of the QSR are discussed in “The Quality System Regulation” section.

The Difference Between Research and Development

• The preamble to the QSR states that research activities are not regulated by the QSR, but development activities are regulated.

• The regulation does not provide guidance for distinguishing between the two activities; however, the preamble does add, “The design control requirements are not intended to apply to the development of concepts and feasibility studies. However, once it decides that a design will be developed, a plan must be established. . . .”

• Most device developers categorize investigations of a general technology as research and application of that technology to a particular product’s development.

• For example, if a device developer creates a new laser technology, that effort would be considered research. Once the developer begins to apply that technology to a particular model of device with specific indications for use and user requirements, then they have begun the development phase and design controls must be applied.

• A device developer’s design control standard operating procedures (SOPs) should clearly describe the point in the development process when design controls apply, and that definition should be consistently followed for all design projects.

Design Control Components

• There are eight components of design controls that stretch from planning for the development effort through design transfer (from development to manufacturing) and maintenance of existing designs.

• These controls apply to all class II and III medical devices and a small number of class I devices.

• The purpose of these controls is to ensure that devices are developed in a rational manner, in compliance with the firm’s existing design control SOPs.
  *

  Design Activity	Personnel Involved	Examples of Issues
  Design and development planning	Development, marketing, and management	•Determine timing for design reviews •Determine documentation requirements and departmental documentation responsibilities •Determine overall project timelines and budget
  Design input	Development, management, sales and marketing, quality, and regulatory	•Identify users of the new device •Specify where the new device will be used •Describe the operating environment for the device •Document how long the new device will be used •Determine the user/patients requirements •Comply with regulations and standards •Develop specifications for the device •Develop, select, and evaluate components and suppliers •Develop and approve labels, user instructions, and training materials •Develop packaging •Document the processes and details of the device design •If applicable, develop a service program
  Design output	Development	•Execute the design •Update risk analysis during the design process
  Design review	Development, management, and others, as needed, including one person not directly involved in the design effort	•Determine if the design meets customer needs •Confirm that manufacturability and reliability issues are adequately addressed •Establish that human factors’ issues are adequately addressed •Determine frequency of design reviews. At least one during the development program. Complex programs may have more, depending upon the developer’s procedures
  Design verification	Development	•Confirm that the design outputs meet the design input requirements by reviewing data from tests, inspections, analysis, and formative human factors studies
  Design validation	Development, management, and clinical	•Perform under defined operating conditions on initial production units, or its equivalent •Include software validation and risk analysis, here as appropriate •Ensure that devices conform to defined user needs and intended uses •Include testing under actual or simulated use conditions •Validation plans, methods, reports, and review must be conducted according to approved SOPs •Include actual use clinical trials, simulated use testing, and other evaluations
  Design transfer	Development, management, quality, and manufacturing	•Prepare a plan for the transfer of all the design components to manufacturing •Develop manufacturing facilities and utilities •Develop and validate manufacturing processes •Assure that all affected personnel are adequately trained •Assure that all manufacturing and quality systems function according to specifications •Transfer portions of the design in an incremental manner, rather than all at once
  Design changes	Development and management	•Assure that design changes are tracked, verified, and validated •Assure that corrective actions are completed •Assure that the DHF is kept current and includes all design revisions

• If a company is just starting to develop a medical device for the first time, the design control process must be fully described in SOPs and fully implemented before the development planning begins.

• Design controls are closely linked to many other QSR components and the entire system must work together to produce good product; Refer to “The Quality System Regulation” section for discussion of the other components of the QSR.

• The design control regulation sets requirements for the development process; Firms must prepare and follow SOPs that comply with the regulations and that fully describe how the firm will meet all relevant regulatory requirements.

• All the relevant activities must be fully documented in the firm’s design history file (DHF).

• For example, the regulation requires device developers to prepare a list of design inputs; Just like every other design control-related document, this list cannot be considered a static document. As the design process progresses, inputs are modified, added, or subtracted. The design input file must be maintained as a current document throughout the development process.

• Another important design control function is the design review; At least once during the design process, and more frequently for a complex design effort, the design must be reviewed to ensure that the design satisfies the design input requirements for the intended use of the device and the needs of the user.

• All other sources of design information, including design output reports, design verification documentation, and even actual prototypes should be part of this review; Most importantly, for regulatory compliance, a report must document all the design review activities and their results and list the individuals that participated in the review.

• The regulation requires that at least one member of the review team be an independent reviewer who has not been directly involved with the design effort.

• Two other tasks must be considered throughout the device development process; Risk analysis should be conducted early in the design process and continually updated as the design evolves.

• The purpose of risk analysis is to identify potential risks associated with the device and evaluate their effect: If a significant risk is identified, it must be mitigated (reduced), preferably by modifying the design. At the end of the design process, all substantial risks should be mitigated.

• One method used to identify user-related risks is human factors evaluation; The FDA has been using human factors evaluations for an increasing number of devices; For example, in 2009 and 2010 the FDA began efforts to address the high number of infusion pump recalls and patient deaths.

• The FDA currently expects other devices, especially those that are used by patients and lay caregivers to undergo rigorous human factors evaluations.

• Formative human factor studies are frequently relatively small studies where potential users are observed as they use prototype devices; Lessons learned from these studies stimulate design changes as potential risks are identified.

• Once a final design has been established, a summative human factors study, or in some cases, a clinical trial is conducted to evaluate device performance in the hands of the expected user population; This last type of testing is considered design validation.

Medical Device Clinical Research

• Once the regulatory pathway has been determined and development is underway, clinical data may be necessary; Keep in mind that the vast majority of 510(k) notifications do not contain clinical data.

• Unlike the pharmaceutical model, there are three levels of regulation of medical device clinical research; Some research is exempted from the investigational device exemption (IDE) regulation; some research is subject to just some sections of the IDE regulation; and other types of research are subject to all sections of the IDE regulation

Exempted Studies

• Most exempted studies involve either previously cleared or approved devices or investigational in vitro diagnostic devices.

• If a sponsor wishes to conduct a study that, for example, compares the performance of their own previously cleared device with the performance of their competitor’s previously cleared device, that study would be exempt from the IDE regulations, so long as both devices are used for their cleared indications; No prior FDA review or approval of the study is necessary.

• Of course, due to privacy concerns and institutional regulations, any human clinical trial should use an informed consent form and be reviewed and approved by the appropriate institutional review board (IRB).

• Most in vitro diagnostic field trials are also exempt, so long as invasive means are not used to collect samples, performing the investigational assay does not consume sample material needed for medically necessary approved assays, and the data obtained from the investigational assay are not used to make treatment decisions.

• Also, in some cases when archived de-identified samples are used for in vitro diagnostic field trials, informed consent may not be necessary.

• Animal studies and custom device studies are also exempt from the IDE regulation.

Nonsignificant Risk Studies

• Many studies that do not involve highly invasive devices, risky procedures, and/or frail patients can be conducted under the nonsignificant risk (NSR) provisions of the IDE regulation.

• These provisions provide an intermediate level of control for the study without requiring the study sponsor to prepare and file an IDE.

• When a sponsor determines that a study is NSR, no FDA involvement is required, although many sponsors will consult with the FDA to confirm that the study is indeed NSR and that its design is consistent with the FDA expectations.

• Each IRB that reviews an NSR study must document three conclusions; First, that they concur with the sponsor’s NSR determination; second, that the study protocol is approved; and third, that the consent form is approved.

• If just one IRB formally determines that a study is not NSR, then the sponsor must report this to the ODE; If all IRBs approve the study, it may proceed. In this case, the local IRBs monitor the progress of the study according to their own SOPs, and the FDA is not involved in the process.

Significant Risk Studies

• Significant risk studies require an approved IDE to treat patients in the United States.

• Typical significant risk studies involve implantable devices or devices that introduce significant quantities of energy into the body; Studies with devices that sustain or support life are nearly always considered significant risk.

• If a study sponsor is unsure of the risk status of a study, consultation with the appropriate branch within the ODE should be considered.

The Investigational Device Exemption

• The IDE serves the same function for a significant risk medical device clinical trial as the investigational new drug (IND), described in Chapter 2, does for pharmaceutical clinical trials.

• The submission contains data that are similar in many respects to data contained in an IND.

• There are, however, some significant differences between the two submission types due to the differences in regulatory requirements between devices and drugs.

• Although preclinical testing data are included in both the submissions, the data in an IDE conforms to the ISO 10993 biocompatability testing standard as modified by the FDA, rather than the “International Conference on Harmonization (ICH)” guidance.

• Relevant FDA guidance documents (special controls) may also list additional data expectations.

• The IDE regulation requires an investigational plan but does not specify an investigator brochure; The international ISO 14155 medical device clinical research standard does require an investigator brochure.

• The IDE regulation also requires that the sponsor include a clinical monitoring SOP in the submission.

• Under the cost recovery provision of the IDE regulation, the sponsor may charge for the investigational device, so long as only research and development and manufacturing costs are recovered.

• An investigator agreement serves the function of the Form FDA 1572, used for pharmaceutical studies.

Unique Aspects of Medical Device Studies

• The informed consent, financial disclosure, and IRB regulations described in Chapter 9 apply equally for medical device studies; Provisions of the IND regulation and ICH guidelines do not apply to medical device studies.

• Test article administration is frequently a prime concern in trials of therapeutic devices; In most drug trials, IV, IM, or PO administration of the test article is a trivial concern that is hardly discussed. The manner in which a surgical device is used or the technique by which an implantable device is placed in the body can mean the difference between success and failure in the trial.

• Because of this, investigator training is a critical aspect of many device trials; Protocol compliance while using the device and while recording data is also a critical issue. In addition, the clinical research associate (CRA) is called upon to transmit technical data between the technical development staff and investigators.

• Unlike most pharmaceutical studies that are both masked and randomized, the vast majority of device studies are not masked. Most of the time, it is not possible or ethical to mask the device, especially if the device is an implant or a surgical device; Often it is possible to mask a patient assessor to reduce bias.

• First, the ICH guidelines only apply to pharmaceutical studies, not to medical device studies; The greatest effect is seen on adverse device effects analysis and reporting.

• The IDE regulations permit an investigator to analyze a potential adverse device effect for 10 days before reporting it to the local IRB and the sponsor (most sponsors impose a 24-hour reporting period); The sponsor then has another 10 days to evaluate the event to determine if it should be reported to the ODE, all reviewing IRBs, and all participating investigators.

• The IDE regulations do require the sponsor to directly communicate this information to the IRBs; This responsibility cannot be delegated to the investigators. While ICH guidances do not apply, some, such as those that describe format and contents of clinical study reports, may offer device companies good suggestions for organizing their study reports.

• The IDE regulation also does not require the preparation of an investigator brochure; In some cases, especially for multinational studies, a sponsor may choose to prepare such a document, even though it is not required.

• The Form FDA 1572 is another inapplicable document; It requires the investigator to comply with key provisions of the IND regulation, so it is not relevant to device studies. In its place, we have the investigator agreement. It serves roughly the same purpose as the Form FDA 1572. Its contents are specified in 21 CFR 812.43(c).

• Although not required by the regulation, many sponsors ask that the principal investigator list the subinvestigators in the agreement, as this list will simplify the gathering of financial disclosure information.

• There is usually a second investigator agreement, not subject to the FDA review, that covers financial compensation, publishing priorities, and other unregulated activities.

• Lastly, the cost recovery provision of the IDE regulation [21 CFR 812.20(b)(8)] permits the sponsor to charge for the device; The sponsor can charge enough to recover research and development costs. This provision cannot be used to commercialize an investigational device.

The 510(k) Premarket Notification

• More than 3000 medical devices are cleared on to the US market every year through the 510(k) premarket notification process; This represents approximately half the new devices that appear in the US market in a given year. The 510(k) process is relatively rapid, flexible, and adaptable to many different device types and risk levels.

• The goal of the 510(k) process is the following: Demonstration of substantial equivalence to a device that was on the US market prior to May 28, 1976 or to a device that has already gone through the 510(k) clearance process.

• Devices that have successfully gone through the 510(k) process are described as “510(k) cleared.” A distinction is made between those devices that have been reviewed according to the substantial equivalence standard from those that have been reviewed according to the PMA application, safety, and effectiveness standard. PMA devices are “approved.”

• The previously cleared device included for comparison purposes in a 510(k) is called the predicate device; A 510(k) may contain multiple predicate devices that address various features of the device.

• The device designers should be able to provide regulatory personnel with assistance, identifying key technological characteristics that demonstrate substantial equivalence; These data should already be part of the design inputs required as part of design controls.

• Generally, little, if any, manufacturing data are included in a 510(k); Sterile devices will include information on the sterilization process, including sterilization process validation activities and the sterilization assurance level. In vitro diagnostic products will frequently include data on the production of key reagents such as antibodies or nucleic acid probes.

• The other part of substantial equivalence relates to the indication for use; Frequently, one medical device can be used for many indications in a variety of medical specialties. When new indications are added, those indications must be cleared in a traditional or abbreviated 510(k). The 510(k) must cite a predicate device with the same indication for use.

• Two FDA databases, the 510(k) database and the classification database, can be very helpful. The 510(k) database is especially useful when one knows either the name of potential predicate devices or the manufacturer of the device. The classification database can be used to identify a particular device type and its corresponding product code. One can then transfer the product code to the 510(k) database and generate a listing of all similar devices. Sales and marketing staffs and competitor Websites are also excellent

Flashcard #1
Term: Class I Medical Devices
Definition: Simplest devices, posing the fewest risks and subject to general controls.

Flashcard #2
Term: Examples of Class I Medical Devices
Definition: Examples: toothbrushes, oxygen masks, irrigating syringes.

Flashcard #3
Term: Class II Medical Devices
Definition: Moderate risk devices that require 510(k) premarket notification clearance before commercialization.

Flashcard #4
Term: Examples of Class II Medical Devices
Definition: Examples: ultrasound imaging systems, Holter cardiac monitors, pregnancy test kits.

Flashcard #5
Term: Class III Medical Devices
Definition: Require PMA approval before marketing and are not substantially equivalent to any class II device.

Flashcard #6
Term: Characteristics of Class III Medical Devices
Definition: Usually technologically innovative devices.

Reclassification is when the FDA approves a petition to downclassifying a device from class III to class II or I. This reexamination can be initiated by the FDA or industry to focus on higher-risk products or due to successful reclassification petitions by industry groups.

A regulatory patent, often called the creation of a 'regulatory barrier of entry,' occurs when a device developer chooses the more complicated class III PMA designation route, even if a 510(k) pathway is possible. Device companies may prefer a regulatory patent if the developer does not have a strong intellectual property position but has sufficient resources to conduct clinical trials. This strategy can result in a regulatory barrier of entry for other, less well-funded organizations.

Class I Medical Devices
Definition: Simplest devices, posing the fewest risks and subject to general controls.

Flashcard #2
Term: Examples of Class I Medical Devices
Definition: Examples: toothbrushes, oxygen masks, irrigating syringes.

Flashcard #3
Term: Class II Medical Devices
Definition: Moderate risk devices that require 510(k) premarket notification clearance before commercialization.

Flashcard #4
Term: Examples of Class II Medical Devices
Definition: Examples: ultrasound imaging systems, Holter cardiac monitors, pregnancy test kits.

Flashcard #5
Term: Class III Medical Devices
Definition: Require PMA approval before marketing and are not substantially equivalent to any class II device.

Flashcard #6
Term: Characteristics of Class III Medical Devices
Definition: Usually technologically innovative devices.

Here are 5 examples of medical devices for each class:

Class I Medical Devices:

1. Toothbrushes

2. Oxygen masks

3. Irrigating syringes

4. Bandages

5. Tongue depressors

Class II Medical Devices:

1. Ultrasound imaging systems

2. Holter cardiac monitors

3. Pregnancy test kits

4. Electric wheelchairs

5. Infusion pumps

Class III Medical Devices:

1. Implantable pacemakers

2. Heart valves

3. Cochlear implants

4. Deep brain stimulators

5. Implantable infusion pumps